Ignite Creation Date:
2025-12-24 @ 5:44 PM
Ignite Modification Date:
2025-12-29 @ 2:39 AM
Study NCT ID:
NCT04614168
Status:
ACTIVE_NOT_RECRUITING
Last Update Posted:
2025-12-17
First Post:
2020-10-07
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Maximising Time With a Normal Blood Glucose to Restore the Glucagon Response in Type 1 Diabetes
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24', 'submissionTracking': {'firstMcpInfo': {'postDateStruct': {'date': '2025-09-25', 'type': 'ESTIMATED'}}}}, 'conditionBrowseModule': {'meshes': [{'id': 'D003922', 'term': 'Diabetes Mellitus, Type 1'}, {'id': 'D007003', 'term': 'Hypoglycemia'}, {'id': 'D007333', 'term': 'Insulin Resistance'}], 'ancestors': [{'id': 'D003920', 'term': 'Diabetes Mellitus'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}, {'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D001327', 'term': 'Autoimmune Diseases'}, {'id': 'D007154', 'term': 'Immune System Diseases'}, {'id': 'D006946', 'term': 'Hyperinsulinism'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D007332', 'term': 'Insulin Infusion Systems'}, {'id': 'D050528', 'term': 'Diet, Carbohydrate-Restricted'}], 'ancestors': [{'id': 'D016503', 'term': 'Drug Delivery Systems'}, {'id': 'D004358', 'term': 'Drug Therapy'}, {'id': 'D013812', 'term': 'Therapeutics'}, {'id': 'D007260', 'term': 'Infusion Pumps'}, {'id': 'D004864', 'term': 'Equipment and Supplies'}, {'id': 'D001187', 'term': 'Artificial Organs'}, {'id': 'D013523', 'term': 'Surgical Equipment'}, {'id': 'D004035', 'term': 'Diet Therapy'}, {'id': 'D044623', 'term': 'Nutrition Therapy'}, {'id': 'D004032', 'term': 'Diet'}, {'id': 'D009747', 'term': 'Nutritional Physiological Phenomena'}, {'id': 'D000066888', 'term': 'Diet, Food, and Nutrition'}, {'id': 'D010829', 'term': 'Physiological Phenomena'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'shareen.forbes@ed.ac.uk', 'phone': '0131 242 6740', 'title': 'Prof. Shareen Forbes', 'organization': 'University of Edinburgh'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': 'From recruitment of participant to study completion (8 months per participants).', 'eventGroups': [{'id': 'EG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.', 'otherNumAtRisk': 5, 'deathsNumAtRisk': 5, 'otherNumAffected': 0, 'seriousNumAtRisk': 5, 'deathsNumAffected': 0, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.', 'otherNumAtRisk': 11, 'deathsNumAtRisk': 11, 'otherNumAffected': 0, 'seriousNumAtRisk': 11, 'deathsNumAffected': 0, 'seriousNumAffected': 1}], 'seriousEvents': [{'term': 'Proliferative retinopathy', 'notes': '3 month eye screening one participant HCL group was diagnosed with proliferative retinopathy in their left eye (R1 to R4). They were referred to ophthalmology. Repeat screening by ophthalmology showed R1 in both eyes.', 'stats': [{'groupId': 'EG000', 'numAtRisk': 5, 'numEvents': 0, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 11, 'numEvents': 1, 'numAffected': 1}], 'organSystem': 'Eye disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'The Change in Plasma Glucagon Levels (Pmol/L) Measured During Normoglycaemic and Hypoglycaemia', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Delta Clamp 1 (P3-P1)', 'categories': [{'measurements': [{'value': '1.34', 'groupId': 'OG000', 'lowerLimit': '0.46', 'upperLimit': '4.52'}, {'value': '1.68', 'groupId': 'OG001', 'lowerLimit': '0.96', 'upperLimit': '3.35'}]}]}, {'title': 'Delta Clamp 2 (P3-P1)', 'categories': [{'measurements': [{'value': '2.26', 'groupId': 'OG000', 'lowerLimit': '0.52', 'upperLimit': '3.64'}, {'value': '0.31', 'groupId': 'OG001', 'lowerLimit': '0.00', 'upperLimit': '1.53'}]}]}], 'analyses': [{'pValue': '>0.99', 'groupIds': ['OG000'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.64', 'groupIds': ['OG001'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEDIAN', 'timeFrame': 'Clamp 1 at baseline and clamp 2 at 8 months', 'description': 'The delta glucagon concentration (pmol/L) from plateau 1 (normoglycaemia- 5.0 mmol/L) to plateau 3 (hypoglycaemia- 2.5 mmol/L). The physiological response in health would be for an increase in glucagon secretion from normo- to hypoglycaemia.', 'unitOfMeasure': 'pmol/L', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED', 'populationDescription': 'Three participants withdrew from group 1 after the 1st clamp study visit. They were excluded from the study analysis.'}, {'type': 'SECONDARY', 'title': 'Time in Glycaemic Range (3.9-10mmol/L)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '51.46', 'spread': '13.63', 'groupId': 'OG000'}, {'value': '53.55', 'spread': '14.48', 'groupId': 'OG001'}]}]}, {'title': 'Midpoint', 'categories': [{'measurements': [{'value': '44.26', 'spread': '11.5', 'groupId': 'OG000'}, {'value': '78.01', 'spread': '6.32', 'groupId': 'OG001'}]}]}, {'title': 'Endpoint', 'categories': [{'measurements': [{'value': '39.64', 'spread': '20.15', 'groupId': 'OG000'}, {'value': '76.85', 'spread': '9.61', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.37', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '<0.0001', 'groupIds': ['OG001'], 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline (study entry), midpoint at 4 months and endpoint at 8 months', 'description': 'Percentage time spent in target glycaemic range.', 'unitOfMeasure': 'Percentage', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Time Spent Below the Target Glycaemic Range (<3.9mmol/L)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '1.02', 'spread': '0.62', 'groupId': 'OG000'}, {'value': '2.13', 'spread': '3.17', 'groupId': 'OG001'}]}]}, {'title': 'Midpoint', 'categories': [{'measurements': [{'value': '2.25', 'spread': '3.50', 'groupId': 'OG000'}, {'value': '0.94', 'spread': '0.55', 'groupId': 'OG001'}]}]}, {'title': 'Endpoint', 'categories': [{'measurements': [{'value': '2.18', 'spread': '3.85', 'groupId': 'OG000'}, {'value': '0.74', 'spread': '0.57', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.20', 'groupIds': ['OG001'], 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.95', 'groupIds': ['OG000'], 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline (study entry), midpoint at 4 months and endpoint at 8 months', 'description': 'Percentage of time spent below the target glycaemic range', 'unitOfMeasure': 'Percentage', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Time Spent Above the Target Glycaemic Range (>10mmol/L)', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '21.94', 'spread': '13.93', 'groupId': 'OG000'}, {'value': '33.64', 'spread': '12.42', 'groupId': 'OG001'}]}]}, {'title': 'Midpoint', 'categories': [{'measurements': [{'value': '21.67', 'spread': '13.55', 'groupId': 'OG000'}, {'value': '18.93', 'spread': '4.66', 'groupId': 'OG001'}]}]}, {'title': 'Endpoint', 'categories': [{'measurements': [{'value': '23.42', 'spread': '17.23', 'groupId': 'OG000'}, {'value': '19.06', 'spread': '5.87', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.58', 'groupIds': ['OG000'], 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.01', 'groupIds': ['OG001'], 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline (study entry), midpoint at 4 months and endpoint at 8 months', 'description': 'Percentage of time spent above the target glycaemic range', 'unitOfMeasure': 'Percentage', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'The Change in Plasma Cortisol (ng/mL) Levels Measured During Normoglycaemic and Hypoglycaemia', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Delta P3-P1 Clamp 1', 'categories': [{'measurements': [{'value': '146', 'spread': '126', 'groupId': 'OG000'}, {'value': '72.52', 'spread': '91.48', 'groupId': 'OG001'}]}]}, {'title': 'Delta P3-P1 Clamp 2', 'categories': [{'measurements': [{'value': '195.2', 'spread': '115.9', 'groupId': 'OG000'}, {'value': '11.31', 'spread': '37.14', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.13', 'groupIds': ['OG000'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.01', 'groupIds': ['OG001'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Clamp 1 at baseline and clamp 2 at 8 months', 'description': 'Delta cortisol from P1 (5.0 mmol/L) to P3 (2.5 mmol/L)', 'unitOfMeasure': 'ng/mL', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'The Change in Plasma Adrenaline (pg/mL) Levels Measured During Normoglycaemic and Hypoglycaemia', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Clamp 1', 'categories': [{'measurements': [{'value': '260', 'groupId': 'OG000', 'lowerLimit': '78.5', 'upperLimit': '499'}, {'value': '187', 'groupId': 'OG001', 'lowerLimit': '27.25', 'upperLimit': '658.5'}]}]}, {'title': 'Clamp 2', 'categories': [{'measurements': [{'value': '413', 'groupId': 'OG000', 'lowerLimit': '267.5', 'upperLimit': '524.5'}, {'value': '252.5', 'groupId': 'OG001', 'lowerLimit': '172.8', 'upperLimit': '696.5'}]}]}], 'analyses': [{'pValue': '0.63', 'groupIds': ['OG000'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.36', 'groupIds': ['OG001'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEDIAN', 'timeFrame': 'Clamp 1 at baseline and clamp 2 at 8 months', 'description': 'Delta adrenaline from plateau 1 (5mmol/L) to plateau 3 (2.5 mmol/L)', 'unitOfMeasure': 'Delta pg/mL', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'The Change in Plasma Noradrenaline (pg/mL) Levels Measured During Normoglycaemic and Hypoglycaemia', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Delta noradrenaline (P3-P1) Clamp 1', 'categories': [{'measurements': [{'value': '49', 'groupId': 'OG000', 'lowerLimit': '-132', 'upperLimit': '225'}, {'value': '-10.56', 'groupId': 'OG001', 'lowerLimit': '-50.25', 'upperLimit': '38.75'}]}]}, {'title': 'Delta noradrenaline (P3-P1) Clamp 2', 'categories': [{'measurements': [{'value': '-43', 'groupId': 'OG000', 'lowerLimit': '-133', 'upperLimit': '56'}, {'value': '90.5', 'groupId': 'OG001', 'lowerLimit': '3.75', 'upperLimit': '172.3'}]}]}], 'analyses': [{'pValue': '0.44', 'groupIds': ['OG000'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.02', 'groupIds': ['OG001'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEDIAN', 'timeFrame': 'Clamp 1 at baseline and clamp 2 at 8 months', 'description': 'The change in noradrenaline concentration from plateau 1 (5 mmol/L) to plateau 3 (2.5 mmol/L).', 'unitOfMeasure': 'pg/mL', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Endogenous Glucose Production', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Delta glucose rate of appearance P3-P1 Clamp 1', 'categories': [{'measurements': [{'value': '-0.16', 'spread': '0.21', 'groupId': 'OG000'}, {'value': '-0.12', 'spread': '0.16', 'groupId': 'OG001'}]}]}, {'title': 'Delta glucose rate of appearance P3-P1 Clamp 2', 'categories': [{'measurements': [{'value': '-0.22', 'spread': '0.16', 'groupId': 'OG000'}, {'value': '-0.8', 'spread': '0.16', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.38', 'groupIds': ['OG000'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.88', 'groupIds': ['OG001'], 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Clamp 1 at baseline and clamp 2 at 8 months', 'description': 'The change in the glucose rate of appearance from plateau 1 (5mmol/L) to plateau 3 (2.5 mmol/L)', 'unitOfMeasure': 'mg/kg/minute', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'HbA1c', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000', 'lowerLimit': '-4.5', 'upperLimit': '4'}, {'value': '-12', 'groupId': 'OG001', 'lowerLimit': '-18', 'upperLimit': '-4'}]}]}], 'analyses': [{'pValue': '0.0094', 'groupIds': ['OG000', 'OG001'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEDIAN', 'timeFrame': 'Baseline (study entry) endpoint (8 months)', 'description': 'Delta HbA1c from baseline to study endpoint.', 'unitOfMeasure': 'mmol/mol', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Quality of Life at Trial Entry and End.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '81', 'spread': '6.52', 'groupId': 'OG000'}, {'value': '79.36', 'spread': '12.33', 'groupId': 'OG001'}]}]}, {'title': 'Endpoint', 'categories': [{'measurements': [{'value': '82', 'spread': '11.51', 'groupId': 'OG000'}, {'value': '80.27', 'spread': '9.96', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '>0.99', 'groupIds': ['OG000'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.82', 'groupIds': ['OG001'], 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline (study entry) endpoint (8 months)', 'description': 'Measured using the EQ5D-5L- -VAS. Number on scale of 0-100 to assess wellbeing on that day. 100 being the most well.', 'unitOfMeasure': 'Number', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Emotional Distress Related to Diabetes at Trial Entry and End.', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '2.18', 'spread': '0.64', 'groupId': 'OG000'}, {'value': '2.2', 'spread': '1.15', 'groupId': 'OG001'}]}]}, {'title': 'Endpoint', 'categories': [{'measurements': [{'value': '1.96', 'spread': '0.66', 'groupId': 'OG000'}, {'value': '1.58', 'spread': '0.49', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.13', 'groupIds': ['OG000'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.03', 'groupIds': ['OG001'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline (study entry) endpoint (8 months)', 'description': 'Diabetes Distress Scale (DDS-1)- a 28-item self-reporting scale. Each item can be scored from 1 (not a problem) to 6 (a very serious problem). This questionnaire will be completed at study entry and study end. Data presented is the DDS total score.', 'unitOfMeasure': 'Numerical score', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Fear of Hypoglycaemic', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Behaviour Scale Baseline', 'categories': [{'measurements': [{'value': '22', 'spread': '4.24', 'groupId': 'OG000'}, {'value': '20.55', 'spread': '4.03', 'groupId': 'OG001'}]}]}, {'title': 'Behaviour Scale Endpoint', 'categories': [{'measurements': [{'value': '19.2', 'spread': '8.11', 'groupId': 'OG000'}, {'value': '18.82', 'spread': '4.79', 'groupId': 'OG001'}]}]}, {'title': 'Worry scale Baseline', 'categories': [{'measurements': [{'value': '24', 'spread': '9.34', 'groupId': 'OG000'}, {'value': '24.25', 'spread': '15.85', 'groupId': 'OG001'}]}]}, {'title': 'Worry Scale Endpoint', 'categories': [{'measurements': [{'value': '21.4', 'spread': '15.39', 'groupId': 'OG000'}, {'value': '12.88', 'spread': '9.78', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.25', 'groupIds': ['OG000'], 'groupDescription': 'Behaviour subscale', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.63', 'groupIds': ['OG000'], 'groupDescription': 'Worry subscale', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.35', 'groupIds': ['OG001'], 'groupDescription': 'Behaviour subscale', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.09', 'groupIds': ['OG001'], 'groupDescription': 'Worry subscale', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline (study entry) endpoint (8 months)', 'description': 'Measured using the Hypoglycaemia Fear Survey (HFS)- this survey consists of two subscales- Baseline (study entry) endpoint (8 months) Behaviour and Worry. There are 28 items in the survey that the participant ranks from Never (0) to Almost Always (4). Higher scores indicate fear of hypoglycaemia. In the Behaviour subscale the lowest possible score in 0 and the highest possible score is 60. In the Worry subscale the lowest possible score is 0 and the highest is 72.\n\nParticipants will complete this questionnaire at study entry and study end.', 'unitOfMeasure': 'Numerical score', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Confidence of Managing Hypoglycaemia', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Baseline', 'categories': [{'measurements': [{'value': '27.2', 'spread': '5.17', 'groupId': 'OG000'}, {'value': '27.64', 'spread': '7.63', 'groupId': 'OG001'}]}]}, {'title': 'Endpoint', 'categories': [{'measurements': [{'value': '29.2', 'spread': '5.31', 'groupId': 'OG000'}, {'value': '31.27', 'spread': '3.9', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.25', 'groupIds': ['OG000'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.09', 'groupIds': ['OG001'], 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Baseline (study entry) endpoint (8 months)', 'description': "Measured using the Hypoglycaemic Confidence Scale- this is a 9 item scale. The participant rates each item from Not Confident at All to Very Confident. Participants will complete this questionnaire at study entry and study end. Higher scores mean more confidence. 'Not confident' at lower end of scale scored as 1 and 'very confident' at top of the scale scored as 4. Min score is 9 and max score is 36.", 'unitOfMeasure': 'Numerical score', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Hypoglycaemia Awareness', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Clamp 1 Plateau 1', 'categories': [{'measurements': [{'value': '24', 'groupId': 'OG000', 'lowerLimit': '22.5', 'upperLimit': '31.5'}, {'value': '27', 'groupId': 'OG001', 'lowerLimit': '18', 'upperLimit': '32'}]}]}, {'title': 'Clamp 1 Plateau 2', 'categories': [{'measurements': [{'value': '35', 'groupId': 'OG000', 'lowerLimit': '29.5', 'upperLimit': '60.5'}, {'value': '25', 'groupId': 'OG001', 'lowerLimit': '19', 'upperLimit': '50'}]}]}, {'title': 'Clamp 1 Plateau 3', 'categories': [{'measurements': [{'value': '39.64', 'groupId': 'OG000', 'lowerLimit': '30.5', 'upperLimit': '62.5'}, {'value': '34', 'groupId': 'OG001', 'lowerLimit': '24', 'upperLimit': '64'}]}]}, {'title': 'Clamp 2 Plateau 1', 'categories': [{'measurements': [{'value': '34', 'groupId': 'OG000', 'lowerLimit': '23.5', 'upperLimit': '36'}, {'value': '28', 'groupId': 'OG001', 'lowerLimit': '22', 'upperLimit': '36'}]}]}, {'title': 'Clamp 2 Plateau 2', 'categories': [{'measurements': [{'value': '34', 'groupId': 'OG000', 'lowerLimit': '27', 'upperLimit': '64.5'}, {'value': '29', 'groupId': 'OG001', 'lowerLimit': '24', 'upperLimit': '60'}]}]}, {'title': 'Clamp 2 Plateau 3', 'categories': [{'measurements': [{'value': '46', 'groupId': 'OG000', 'lowerLimit': '29.5', 'upperLimit': '71'}, {'value': '47', 'groupId': 'OG001', 'lowerLimit': '26', 'upperLimit': '76'}]}]}], 'analyses': [{'pValue': '0.77', 'groupIds': ['OG000'], 'pValueComment': 'Column factor p-value.', 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.37', 'groupIds': ['OG001'], 'statisticalMethod': 'ANOVA', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEDIAN', 'timeFrame': 'Clamp 1 - study entry, clamp 2 - 8 months', 'description': 'Measured during each clamp study using the Edinburgh Hypoglycaemic Scale- this is a 17 item scale of symptoms of hypoglycaemia. The participant ranks on a scale from Not at all (1) to A Great Deal (7) whether they are experiencing each symptom at the time of the questionnaire being completed. Higher scores mean more hypoglycaemia symptoms. The lowest possible score is 0 and the highest possible score is 119.', 'unitOfMeasure': 'Numerical score', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Trial Making Test', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Trail making A delta clamp 1', 'categories': [{'measurements': [{'value': '-3.05', 'groupId': 'OG000', 'lowerLimit': '-4.55', 'upperLimit': '0.4'}, {'value': '0.00', 'groupId': 'OG001', 'lowerLimit': '-12.0', 'upperLimit': '1.50'}]}]}, {'title': 'Trail making A delta clamp 2', 'categories': [{'measurements': [{'value': '-2.6', 'groupId': 'OG000', 'lowerLimit': '-4.55', 'upperLimit': '0.05'}, {'value': '-1.9', 'groupId': 'OG001', 'lowerLimit': '-7.2', 'upperLimit': '2.4'}]}]}, {'title': 'Trail making B delta clamp 1', 'categories': [{'measurements': [{'value': '11.5', 'groupId': 'OG000', 'lowerLimit': '-10.35', 'upperLimit': '22.8'}, {'value': '-7.8', 'groupId': 'OG001', 'lowerLimit': '-10.0', 'upperLimit': '1.0'}]}]}, {'title': 'Trail making B delta clamp 2', 'categories': [{'measurements': [{'value': '0.7', 'groupId': 'OG000', 'lowerLimit': '-2.98', 'upperLimit': '5.5'}, {'value': '-5.6', 'groupId': 'OG001', 'lowerLimit': '-23.9', 'upperLimit': '-0.9'}]}]}], 'analyses': [{'pValue': '0.88', 'groupIds': ['OG000'], 'groupDescription': 'Trail making A delta clamp 1 compared to clamp 2', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.69', 'groupIds': ['OG000'], 'groupDescription': 'Trail Making B delta clamp 1 compared to clamp 2', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.41', 'groupIds': ['OG001'], 'groupDescription': 'Trail making A delta clamp 1 compared to clamp 2', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.49', 'groupIds': ['OG001'], 'groupDescription': 'Trail making B delta clamp 1 compared to clamp 2', 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEDIAN', 'timeFrame': 'Clamp 1- study entry, clamp 2 - 8 months', 'description': 'Measured during each plateau in a stepped hypoglycaemic clamp study at study entry and study end. Delta score plateau 1 (5 mmol/L) to plateau 3 (2.5 mmol/L) compared between clamp studies. Participants are timed completing the test. Higher scores indicate a longer time to complete the test.', 'unitOfMeasure': 'Minutes', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Digit Span Test', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Digit span forwards clamp1', 'categories': [{'measurements': [{'value': '-1', 'groupId': 'OG000', 'lowerLimit': '-2', 'upperLimit': '0'}, {'value': '-1', 'groupId': 'OG001', 'lowerLimit': '-1', 'upperLimit': '1'}]}]}, {'title': 'Digit span forwards clamp 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000', 'lowerLimit': '-1.5', 'upperLimit': '1.5'}, {'value': '0', 'groupId': 'OG001', 'lowerLimit': '-1', 'upperLimit': '0'}]}]}, {'title': 'Digit span backwards clamp 1', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000', 'lowerLimit': '-1', 'upperLimit': '0'}, {'value': '0', 'groupId': 'OG001', 'lowerLimit': '-1', 'upperLimit': '0'}]}]}, {'title': 'Digit span backwards clamp 2', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000', 'lowerLimit': '-1', 'upperLimit': '2'}, {'value': '0', 'groupId': 'OG001', 'lowerLimit': '0', 'upperLimit': '1'}]}]}], 'analyses': [{'pValue': '0.5', 'groupIds': ['OG000'], 'groupDescription': 'Digit span forwards', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.5', 'groupIds': ['OG000'], 'groupDescription': 'Digit span backwards', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.53', 'groupIds': ['OG001'], 'groupDescription': 'Digit span forwards', 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.4', 'groupIds': ['OG001'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEDIAN', 'timeFrame': 'Clamp 1- study entry, clamp 2 - 8 months', 'description': 'Measured during each plateau in a stepped hypoglycaemic clamp study at study entry and study end. Difference in change in score from plateau 1 (5mmol/L) to plateau 3 (2.5 mmol/L) compared between clamp studies. Lower scores mean more errors. Forwards- participant repeats the numbers as read. Backwards- the participant repeats the numbers backwards.', 'unitOfMeasure': 'Correct responses', 'dispersionType': 'Inter-Quartile Range', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Digit Symbol Substitution Test', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Delta score clamp 1', 'categories': [{'measurements': [{'value': '-4.4', 'spread': '5.4', 'groupId': 'OG000'}, {'value': '0.82', 'spread': '6.56', 'groupId': 'OG001'}]}]}, {'title': 'Delta score clamp 2', 'categories': [{'measurements': [{'value': '-6.6', 'spread': '13.7', 'groupId': 'OG000'}, {'value': '-4.0', 'spread': '7.1', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.88', 'groupIds': ['OG000'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.06', 'groupIds': ['OG001'], 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Clamp 1- study entry, clamp 2 - 8 months', 'description': 'Measured during each plateau in a stepped hypoglycaemic clamp study at study entry and study end. Difference in score between plateau 1 (5.0 mmol/L) and plateau 3 (2.5 mmol/L) compared between clamp studies. Given 90 seconds to complete as many items as possible. Higher scores mean more items completed in the allotted time.', 'unitOfMeasure': 'Correct responses', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Four Choice Reaction Time Test', 'denoms': [{'units': 'Participants', 'counts': [{'value': '5', 'groupId': 'OG000'}, {'value': '11', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'OG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'classes': [{'title': 'Clamp 1', 'categories': [{'measurements': [{'value': '15.4', 'spread': '7.4', 'groupId': 'OG000'}, {'value': '38.45', 'spread': '63.21', 'groupId': 'OG001'}]}]}, {'title': 'Clamp 2', 'categories': [{'measurements': [{'value': '52.9', 'spread': '20.43', 'groupId': 'OG000'}, {'value': '57.78', 'spread': '60.63', 'groupId': 'OG001'}]}]}], 'analyses': [{'pValue': '0.38', 'groupIds': ['OG000'], 'statisticalMethod': 'Wilcoxon (Mann-Whitney)', 'nonInferiorityType': 'SUPERIORITY'}, {'pValue': '0.27', 'groupIds': ['OG001'], 'statisticalMethod': 't-test, 2 sided', 'nonInferiorityType': 'SUPERIORITY'}], 'paramType': 'MEAN', 'timeFrame': 'Clamp 1- study entry, clamp 2 - 8 months', 'description': 'Measured during each plateau in a stepped hypoglycaemic clamp study at study entry and study end. Difference in score between plateau 1 (5.0mmol/L) and plateau 3 (2.5 mmol/L) compared between clamp studies. Higher scores mean more time taken to complete the task.', 'unitOfMeasure': 'Time (ms)', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'FG001', 'title': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '8'}, {'groupId': 'FG001', 'numSubjects': '11'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '5'}, {'groupId': 'FG001', 'numSubjects': '11'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '3'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Group 1 - Standard Care', 'description': 'Standard diabetes care. They will undergo 3 periods of blinded continuous glucose monitoring (CGM) lasting 20-days at: baseline, 4 and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hyperinsulinaemic-hypoglycaemic clamp study: Participants will commence a primed insulin infusion at 60mU/m2/min along with a variable rate 20% glucose infusion. Blood glucose monitored (BG) every 5 minutes. The glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On 2 occasions participants will complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be stopped.\n\nBlinded CGM: Allows data on BG to be collected without values altering behaviour. Participants continue to monitor their own BG while wearing the device in the blinded mode.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: takes place at the same time as the hyperinsulinaemic hypoglycaemic clamp. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.'}, {'id': 'BG001', 'title': 'Group 2- Automated Insulin Delivery and Low Carbohydrate Diet', 'description': 'Automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ and Dexcom G6 continuous glucose monitor (CGM). They will be asked to follow a low-carbohydrate diet (30-40g of carbs/meal). Baseline 20-day period of blinded CGM. Participants in this group will undergo a stepped hypoglycaemic clamp study at baseline and 8 months and complete quality of life and diabetes treatment questionnaires.\n\nStepped hypoglycaemic clamp study: Participants commence a primed insulin infusion (rate 60mU/m2/min) and a variable rate 20% glucose infusion. Blood glucose (BG) monitored every 5 minutes. Glucose infusion will be altered to achieve BG plateaus of: 5, 3 and 2.5mmol/l. Each lasting 40 minutes. During each plateau blood samples will be taken 3 times for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. Twice during each plateau participants complete the Edinburgh hypoglycaemia scale and cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test.\n\nInsulin pump: Insulin pump with a built-in algorithm automatic insulin adjustment.\n\nCGM: CGM sends data to the insulin pump to allow automatic insulin adjustment.\n\nLow carbohydrate diet: 30-40g of carbs/meal.\n\nBlinded CGM: data on BG collected without values altering behaviour.\n\nStable isotope studies- D2 Glucose and D5 Glycerol: These studies will take place at the same time as the hypoglycaemic clamp.'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '35.9', 'spread': '11.3', 'groupId': 'BG000'}, {'value': '42.9', 'spread': '9.5', 'groupId': 'BG001'}, {'value': '39.95', 'spread': '10.63', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex/Gender, Customized', 'classes': [{'title': 'Female', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '10', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Race and Ethnicity Not Collected', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants', 'populationDescription': 'Race and Ethnicity were not collected from any participant.'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United Kingdom', 'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Age Diagnosed (Years)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '7', 'groupId': 'BG000', 'lowerLimit': '3', 'upperLimit': '32'}, {'value': '20', 'groupId': 'BG001', 'lowerLimit': '7', 'upperLimit': '31'}, {'value': '16.5', 'groupId': 'BG002', 'lowerLimit': '4.75', 'upperLimit': '31.25'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'Years', 'dispersionType': 'INTER_QUARTILE_RANGE'}, {'title': 'Time since diagnosis (Years)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '19.2', 'groupId': 'BG000', 'lowerLimit': '14', 'upperLimit': '28.1'}, {'value': '25.5', 'groupId': 'BG001', 'lowerLimit': '11', 'upperLimit': '32'}, {'value': '24.67', 'groupId': 'BG002', 'lowerLimit': '12.5', 'upperLimit': '31.29'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'Years', 'dispersionType': 'INTER_QUARTILE_RANGE'}, {'title': 'HbA1c', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '63', 'groupId': 'BG000', 'lowerLimit': '63', 'upperLimit': '64.8'}, {'value': '61', 'groupId': 'BG001', 'lowerLimit': '57', 'upperLimit': '68'}, {'value': '63', 'groupId': 'BG002', 'lowerLimit': '58', 'upperLimit': '65'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'mmol/mol', 'dispersionType': 'INTER_QUARTILE_RANGE'}, {'title': 'Weight', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '84.5', 'spread': '11.9', 'groupId': 'BG000'}, {'value': '77.33', 'spread': '7.8', 'groupId': 'BG001'}, {'value': '80.35', 'spread': '10.14', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Kg', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'BMI', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '29.34', 'spread': '4.1', 'groupId': 'BG000'}, {'value': '26.18', 'spread': '2.99', 'groupId': 'BG001'}, {'value': '27.51', 'spread': '3.76', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'kg^m2', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Insulin Pump User', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '4', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '7', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}, {'title': 'Time in range (3.9-10 mmol/L)', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '49.05', 'spread': '12.47', 'groupId': 'BG000'}, {'value': '53.55', 'spread': '14.48', 'groupId': 'BG001'}, {'value': '50.39', 'spread': '13.83', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Percentage time spent 3.9-10 mmol/L', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Time <3.9 mmol/L', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '0.71', 'groupId': 'BG000', 'lowerLimit': '0.44', 'upperLimit': '1.78'}, {'value': '0.65', 'groupId': 'BG001', 'lowerLimit': '0.39', 'upperLimit': '3.28'}, {'value': '0.71', 'groupId': 'BG002', 'lowerLimit': '0.39', 'upperLimit': '2.27'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'Percentage', 'dispersionType': 'INTER_QUARTILE_RANGE'}, {'title': 'Time <3.0 mmol/L', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '0.12', 'groupId': 'BG000', 'lowerLimit': '0.00', 'upperLimit': '0.19'}, {'value': '0.13', 'groupId': 'BG001', 'lowerLimit': '0.03', 'upperLimit': '0.52'}, {'value': '0.13', 'groupId': 'BG002', 'lowerLimit': '0.03', 'upperLimit': '0.32'}]}]}], 'paramType': 'MEDIAN', 'unitOfMeasure': 'Percentage', 'dispersionType': 'INTER_QUARTILE_RANGE'}, {'title': 'Time >10 mmol/L', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '25.12', 'spread': '11.73', 'groupId': 'BG000'}, {'value': '33.64', 'spread': '12.42', 'groupId': 'BG001'}, {'value': '30.05', 'spread': '12.57', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Percentage', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Time >13.9 mmol/L', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '21.7', 'spread': '8.77', 'groupId': 'BG000'}, {'value': '15.25', 'spread': '13.75', 'groupId': 'BG001'}, {'value': '17.97', 'spread': '12.07', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Percentage', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'CV Glucose', 'classes': [{'denoms': [{'units': 'Participants', 'counts': [{'value': '8', 'groupId': 'BG000'}, {'value': '11', 'groupId': 'BG001'}, {'value': '19', 'groupId': 'BG002'}]}], 'categories': [{'measurements': [{'value': '38.24', 'spread': '6.8', 'groupId': 'BG000'}, {'value': '35.06', 'spread': '4.94', 'groupId': 'BG001'}, {'value': '36.4', 'spread': '5.85', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'Percentage', 'dispersionType': 'STANDARD_DEVIATION'}]}}, 'documentSection': {'largeDocumentModule': {'largeDocs': [{'date': '2022-09-28', 'size': 1491923, 'label': 'Study Protocol and Statistical Analysis Plan', 'hasIcf': False, 'hasSap': True, 'filename': 'Prot_SAP_001.pdf', 'typeAbbrev': 'Prot_SAP', 'uploadDate': '2025-12-02T06:45', 'hasProtocol': True}]}}, 'protocolSection': {'designModule': {'phases': ['NA'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'BASIC_SCIENCE', 'interventionModel': 'PARALLEL', 'interventionModelDescription': 'Participants will be divided into two groups using stratified sampling to match for age, sex and BMI.'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 24}}, 'statusModule': {'overallStatus': 'ACTIVE_NOT_RECRUITING', 'startDateStruct': {'date': '2021-07-26', 'type': 'ACTUAL'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2025-07', 'completionDateStruct': {'date': '2025-12-26', 'type': 'ESTIMATED'}, 'lastUpdateSubmitDate': '2025-12-02', 'studyFirstSubmitDate': '2020-10-07', 'resultsFirstSubmitDate': '2025-09-05', 'studyFirstSubmitQcDate': '2020-11-02', 'lastUpdatePostDateStruct': {'date': '2025-12-17', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2025-12-02', 'studyFirstPostDateStruct': {'date': '2020-11-03', 'type': 'ACTUAL'}, 'resultsFirstPostDateStruct': {'date': '2025-12-17', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2023-09-22', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'The Change in Plasma Glucagon Levels (Pmol/L) Measured During Normoglycaemic and Hypoglycaemia', 'timeFrame': 'Clamp 1 at baseline and clamp 2 at 8 months', 'description': 'The delta glucagon concentration (pmol/L) from plateau 1 (normoglycaemia- 5.0 mmol/L) to plateau 3 (hypoglycaemia- 2.5 mmol/L). The physiological response in health would be for an increase in glucagon secretion from normo- to hypoglycaemia.'}], 'secondaryOutcomes': [{'measure': 'Time in Glycaemic Range (3.9-10mmol/L)', 'timeFrame': 'Baseline (study entry), midpoint at 4 months and endpoint at 8 months', 'description': 'Percentage time spent in target glycaemic range.'}, {'measure': 'Time Spent Below the Target Glycaemic Range (<3.9mmol/L)', 'timeFrame': 'Baseline (study entry), midpoint at 4 months and endpoint at 8 months', 'description': 'Percentage of time spent below the target glycaemic range'}, {'measure': 'Time Spent Above the Target Glycaemic Range (>10mmol/L)', 'timeFrame': 'Baseline (study entry), midpoint at 4 months and endpoint at 8 months', 'description': 'Percentage of time spent above the target glycaemic range'}, {'measure': 'The Change in Plasma Cortisol (ng/mL) Levels Measured During Normoglycaemic and Hypoglycaemia', 'timeFrame': 'Clamp 1 at baseline and clamp 2 at 8 months', 'description': 'Delta cortisol from P1 (5.0 mmol/L) to P3 (2.5 mmol/L)'}, {'measure': 'The Change in Plasma Adrenaline (pg/mL) Levels Measured During Normoglycaemic and Hypoglycaemia', 'timeFrame': 'Clamp 1 at baseline and clamp 2 at 8 months', 'description': 'Delta adrenaline from plateau 1 (5mmol/L) to plateau 3 (2.5 mmol/L)'}, {'measure': 'The Change in Plasma Noradrenaline (pg/mL) Levels Measured During Normoglycaemic and Hypoglycaemia', 'timeFrame': 'Clamp 1 at baseline and clamp 2 at 8 months', 'description': 'The change in noradrenaline concentration from plateau 1 (5 mmol/L) to plateau 3 (2.5 mmol/L).'}, {'measure': 'Endogenous Glucose Production', 'timeFrame': 'Clamp 1 at baseline and clamp 2 at 8 months', 'description': 'The change in the glucose rate of appearance from plateau 1 (5mmol/L) to plateau 3 (2.5 mmol/L)'}, {'measure': 'HbA1c', 'timeFrame': 'Baseline (study entry) endpoint (8 months)', 'description': 'Delta HbA1c from baseline to study endpoint.'}, {'measure': 'Change in Quality of Life at Trial Entry and End.', 'timeFrame': 'Baseline (study entry) endpoint (8 months)', 'description': 'Measured using the EQ5D-5L- -VAS. Number on scale of 0-100 to assess wellbeing on that day. 100 being the most well.'}, {'measure': 'Change in Emotional Distress Related to Diabetes at Trial Entry and End.', 'timeFrame': 'Baseline (study entry) endpoint (8 months)', 'description': 'Diabetes Distress Scale (DDS-1)- a 28-item self-reporting scale. Each item can be scored from 1 (not a problem) to 6 (a very serious problem). This questionnaire will be completed at study entry and study end. Data presented is the DDS total score.'}, {'measure': 'Change in Fear of Hypoglycaemic', 'timeFrame': 'Baseline (study entry) endpoint (8 months)', 'description': 'Measured using the Hypoglycaemia Fear Survey (HFS)- this survey consists of two subscales- Baseline (study entry) endpoint (8 months) Behaviour and Worry. There are 28 items in the survey that the participant ranks from Never (0) to Almost Always (4). Higher scores indicate fear of hypoglycaemia. In the Behaviour subscale the lowest possible score in 0 and the highest possible score is 60. In the Worry subscale the lowest possible score is 0 and the highest is 72.\n\nParticipants will complete this questionnaire at study entry and study end.'}, {'measure': 'Change in Confidence of Managing Hypoglycaemia', 'timeFrame': 'Baseline (study entry) endpoint (8 months)', 'description': "Measured using the Hypoglycaemic Confidence Scale- this is a 9 item scale. The participant rates each item from Not Confident at All to Very Confident. Participants will complete this questionnaire at study entry and study end. Higher scores mean more confidence. 'Not confident' at lower end of scale scored as 1 and 'very confident' at top of the scale scored as 4. Min score is 9 and max score is 36."}, {'measure': 'Hypoglycaemia Awareness', 'timeFrame': 'Clamp 1 - study entry, clamp 2 - 8 months', 'description': 'Measured during each clamp study using the Edinburgh Hypoglycaemic Scale- this is a 17 item scale of symptoms of hypoglycaemia. The participant ranks on a scale from Not at all (1) to A Great Deal (7) whether they are experiencing each symptom at the time of the questionnaire being completed. Higher scores mean more hypoglycaemia symptoms. The lowest possible score is 0 and the highest possible score is 119.'}, {'measure': 'Trial Making Test', 'timeFrame': 'Clamp 1- study entry, clamp 2 - 8 months', 'description': 'Measured during each plateau in a stepped hypoglycaemic clamp study at study entry and study end. Delta score plateau 1 (5 mmol/L) to plateau 3 (2.5 mmol/L) compared between clamp studies. Participants are timed completing the test. Higher scores indicate a longer time to complete the test.'}, {'measure': 'Digit Span Test', 'timeFrame': 'Clamp 1- study entry, clamp 2 - 8 months', 'description': 'Measured during each plateau in a stepped hypoglycaemic clamp study at study entry and study end. Difference in change in score from plateau 1 (5mmol/L) to plateau 3 (2.5 mmol/L) compared between clamp studies. Lower scores mean more errors. Forwards- participant repeats the numbers as read. Backwards- the participant repeats the numbers backwards.'}, {'measure': 'Digit Symbol Substitution Test', 'timeFrame': 'Clamp 1- study entry, clamp 2 - 8 months', 'description': 'Measured during each plateau in a stepped hypoglycaemic clamp study at study entry and study end. Difference in score between plateau 1 (5.0 mmol/L) and plateau 3 (2.5 mmol/L) compared between clamp studies. Given 90 seconds to complete as many items as possible. Higher scores mean more items completed in the allotted time.'}, {'measure': 'Four Choice Reaction Time Test', 'timeFrame': 'Clamp 1- study entry, clamp 2 - 8 months', 'description': 'Measured during each plateau in a stepped hypoglycaemic clamp study at study entry and study end. Difference in score between plateau 1 (5.0mmol/L) and plateau 3 (2.5 mmol/L) compared between clamp studies. Higher scores mean more time taken to complete the task.'}]}, 'oversightModule': {'isUsExport': True, 'oversightHasDmc': True, 'isFdaRegulatedDrug': False, 'isFdaRegulatedDevice': True}, 'conditionsModule': {'keywords': ['Type 1 diabetes', 'Hypoglycaemia', 'Hypoglycemia', 'Glucagon', 'Insulin', 'Low carbohydrate diet', 'Stable isotope'], 'conditions': ['Type 1 Diabetes', 'Type 1 Diabetes Mellitus With Hypoglycemia', 'Hypoglycemia', 'Hypoglycemia Unawareness', 'Glucagon Deficiency', 'Insulin Hypoglycemia']}, 'referencesModule': {'references': [{'pmid': '36600427', 'type': 'DERIVED', 'citation': 'Baxter F, Baillie N, Forbes S. Study protocol: a randomised controlled proof-of-concept real-world study - does maximising time in range using hybrid closed loop insulin delivery and a low carbohydrate diet restore the glucagon response to hypoglycaemia in adults with type 1 diabetes? BMJ Open. 2022 Dec 20;12(12):e054958. doi: 10.1136/bmjopen-2021-054958.'}]}, 'descriptionModule': {'briefSummary': "Almost all people who have had type 1 diabetes for 5 years have a defect in secretion of the hormone Glucagon. This hormone is involved in the body's response to low blood glucose (hypoglycaemia). It works by releasing glucose stores from the liver to bring the blood glucose back to normal. This defect therefore increases the risk of severe hypoglycaemia. The reason for this Glucagon defect in people with Type 1 diabetes is currently unknown.\n\nThis study aims to look at the Glucagon response to hypoglycaemia in 24 people with type 1 diabetes to ascertain whether tight blood glucose control over a period of time improves this response. The investigators aim to achieve good blood glucose control using new generation Automated Insulin Delivery systems (AIDs). This system is made of: an insulin pump, a continuous glucose monitor (CGM) and an algorithm that allows adjustment of insulin delivery based on the blood glucose readings from the CGM. This is the most up to date technology that there is in the management of type 1 diabetes. However, people using this technology often still have problems with high blood glucose after eating. To ensure a very good blood glucose control participants will also follow a low carbohydrate diet to prevent this blood glucose rise after meals.\n\nThe Glucagon response to low blood glucose will be measured at zero and eight months using the hyperinsulinaemic hypoglycaemic clamp technique.", 'detailedDescription': 'This is a feasibility pilot study involving 24 participants with type 1 diabetes. Participants will be recruited from the local type 1 diabetes clinic and insulin pump waiting list. Each participant will enter the trial for a period of 8 months. The investigators aim to test if maximising time in glycaemic range (blood glucose 3.9-10 mmol/L) will restore the glucagon response to insulin-induced hypoglycaemia.\n\nAfter signing informed consent participants will be screened for eligibility against the inclusion and exclusion criteria.\n\nThose who are eligible will have an initial 20-day period of baseline blood glucose data collection. This will be achieved using a blinded continuous glucose monitoring (CGM) device. Participants will continue on their pre-trial diabetes care during this period and will be required to monitor their own blood glucose as normal.\n\nThe participants will be split into two groups using stratified sampling to match for: age, gender and BMI.\n\nGroup 1 will be the control group. Participants in this group will continue on standard diabetes care for the duration of the trial. Participants will be required to undertake two further periods of blinded CGM monitoring at 4 and 8 months.\n\nGroup 2 will be the intervention group. Participants in this group will be placed on the automated insulin delivery (AID) system and asked to follow a low carbohydrate diet of 30-40g of carbohydrate per main meal portion. The AID system will consist of: a Tandem t:slim X2 insulin pump with control IQ technology and a Dexcom G6 continuous glucose monitor. After receiving training on the use of the devices these participants will enter a 2 week study run-in period to become accustomed to the devices and so that device settings can be optimised. As a safety measure these participants will be asked to measure blood ketones at least once daily throughout the trial. Study staff will monitor the data from the participants study devices throughout the trial and adjust settings as required to maximise time in glycaemic range.\n\nAt the beginning and end of the trial all participants will undergo a hyperinsulinaemic hypoglycaemic clamp study to measure their counterregulatory hormone response to hypoglycaemic. Participants will also undergo cognitive tests and assessment of hypoglycaemic awareness during each clamp study.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '21 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Participants with Type 1 diabetes with C-peptide levels less than 200pmol/L.\n* Type 1 diabetes for 5 years or more.\n* HbA1c greater than or equal to 53 mol/mol.\n* Normal renal function.\n* Normal thyroid function.\n* Gold Score 4-7 (indicating impaired awareness of hypoglycaemia)\n* Willingness to monitor blood ketones daily.\n* Use of freestyle libre device is permitted at study entry and may be continued in participants in group 1\n\nExclusion Criteria:\n\n* Current use of a non-approved closed loop / AID system or those on a predictive low glucose suspend insulin pump.\n* Proliferative retinopathy\n* Regular use of real time CGM in the preceding 3 months.\n* History of Diabetic ketoacidosis in the preceding 6 months.\n* Severe hypoglycaemic episode requiring external assistance in the preceding 6 months.\n* Inability to safely use technology used in this study (e.g. impaired vision, memory or dexterity that prevents safe operation of CGM or insulin pump.)\n* Inability to support the technology requirements for the study (e.g. unable to upload study device at home)\n* History of Haemophilia, Cystic Fibrosis, pancreatic disease or complete pancreatectomy, ischaemic heart disease, epilepsy or hypoglycaemia induced seizure\n* History of severe reaction or allergy to adhesive necessary to this study.\n* Unable to adhere to study timetable.\n* Unable to give informed consent.\n* Pregnancy. We will perform a pregnancy test on all eligible participants at baseline.\n* Concurrent use of any non-insulin glucose-lowering agent (including GLP-1 agonists, Symlin, DPP-4 inhibitors, SGLT-2 inhibitors, sulfonylureas. These may lower insulin requirements and predispose to diabetic ketoacidosis.\n* Concurrent use of medication that may affect blood glucose such as SSRIs\n* A condition, which in the opinion of the investigator, would put the patient or study at risk\n* HbA1c greater than or equal to 75 mmol/mol'}, 'identificationModule': {'nctId': 'NCT04614168', 'briefTitle': 'Maximising Time With a Normal Blood Glucose to Restore the Glucagon Response in Type 1 Diabetes', 'organization': {'class': 'OTHER', 'fullName': 'University of Edinburgh'}, 'officialTitle': 'Can Maximising Time in Range Using Automated Insulin Delivery and a Low Carbohydrate Diet Restore the Glucagon Response to Hypoglycaemic in Type 1 Diabetes?', 'orgStudyIdInfo': {'id': 'AC19163'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Group 1 - Standard Care', 'description': 'This group will continue on their standard diabetes care. They will be required to undergo three periods of blinded continuous glucose monitoring each lasting 20-days at: baseline, 4 months and 8 months. Participants in this group will undergo a hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months. They will also complete quality of life and diabetes treatment questionnaires at baseline and 8 months.', 'interventionNames': ['Procedure: Stepped hyperinsulinaemic-hypoglycaemic clamp study', 'Device: Blinded continuous glucose monitor', 'Procedure: Stable isotope studies- D2 Glucose and D5 Glycerol']}, {'type': 'EXPERIMENTAL', 'label': 'Group 2- Automated insulin delivery and low carbohydrate diet', 'description': 'This group will be placed on an automated insulin delivery system: Tandem t:slim x2 insulin pump with Control IQ technology and Dexcom G6 continuous glucose monitor. They will also be asked to follow a low-carbohydrate diet of 30-40g of carbohydrate per main meal. At baseline they will have a 20-day period of blinded continuous glucose monitoring. Participants in this group will undergo a stepped hyperinsulinaemic hypoglycaemic clamp study at baseline and 8 months. They will also complete quality of life and diabetes treatment questionnaires at baseline and 8 months.', 'interventionNames': ['Procedure: Stepped hyperinsulinaemic-hypoglycaemic clamp study', 'Device: Insulin pump', 'Device: Continuous glucose monitor', 'Other: Low carbohydrate diet', 'Device: Blinded continuous glucose monitor', 'Procedure: Stable isotope studies- D2 Glucose and D5 Glycerol']}], 'interventions': [{'name': 'Stepped hyperinsulinaemic-hypoglycaemic clamp study', 'type': 'PROCEDURE', 'description': 'Participants will commence on a primed insulin infusion at a constant rate of 60mU/m2/min along with a variable rate 20% glucose infusion. Participants will have their blood glucose monitored every 5 minutes. The glucose infusion will be altered to achieve the desired blood glucose plateaus of: 5mmol/l, 3mmol/l and 2.5mmol/l. Each plateau will be held for 40 minutes. During each plateau blood samples will be taken on three occasions for: glucagon, cortisol, adrenaline, noradrenaline, D2 glucose and D5 glycerol. On two occasions during each plateau participants will complete the Edinburgh hypoglycaemia scale and the following cognitive tests: trail making test, digit span test, digit symbol substitution test and four choice reaction time test. At the end of the clamp study the insulin infusion will be discontinued and the blood glucose will be allowed to rise to the normal range. Participants will consume lunch before leaving the clinical research facility.', 'armGroupLabels': ['Group 1 - Standard Care', 'Group 2- Automated insulin delivery and low carbohydrate diet']}, {'name': 'Insulin pump', 'type': 'DEVICE', 'otherNames': ['Tandem t:slim x2 with Control IQ technology'], 'description': 'Insulin pump with a built-in algorithm that allows it to work with a CGM device to adjust insulin delivery based on CGM readings.', 'armGroupLabels': ['Group 2- Automated insulin delivery and low carbohydrate diet']}, {'name': 'Continuous glucose monitor', 'type': 'DEVICE', 'otherNames': ['Dexcom G6'], 'description': 'Continuous glucose monitoring device that sends data to the insulin pump to allow the algorithm to adjust insulin delivery. Participants are able to see the glucose data from the device when it is used in open mode.', 'armGroupLabels': ['Group 2- Automated insulin delivery and low carbohydrate diet']}, {'name': 'Low carbohydrate diet', 'type': 'OTHER', 'description': '30-40g of carbohydrate per main meal portion.', 'armGroupLabels': ['Group 2- Automated insulin delivery and low carbohydrate diet']}, {'name': 'Blinded continuous glucose monitor', 'type': 'DEVICE', 'otherNames': ['Dexcom G6'], 'description': 'Allows data on blood glucose to be collected without values altering the behaviour of the participant. Participants have to continue to monitor their own blood glucose while wearing the device in the blinded mode.', 'armGroupLabels': ['Group 1 - Standard Care', 'Group 2- Automated insulin delivery and low carbohydrate diet']}, {'name': 'Stable isotope studies- D2 Glucose and D5 Glycerol', 'type': 'PROCEDURE', 'description': 'These studies will take place at the same time as the hyperinsulinaemic hypoglycaemic clamp studies. Participants will receive a priming dose of each stable isotope followed by a continuous infusion for the remainder of the clamp study.', 'armGroupLabels': ['Group 1 - Standard Care', 'Group 2- Automated insulin delivery and low carbohydrate diet']}]}, 'contactsLocationsModule': {'locations': [{'city': 'Edinburgh', 'country': 'United Kingdom', 'facility': 'Edinburgh Royal Infirmary/University of Edinburgh', 'geoPoint': {'lat': 55.95206, 'lon': -3.19648}}], 'overallOfficials': [{'name': 'Shareen Forbes, MBChB, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Edinburgh'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Edinburgh', 'class': 'OTHER'}, 'collaborators': [{'name': 'NHS Lothian', 'class': 'OTHER_GOV'}, {'name': 'The Leona M. and Harry B. Helmsley Charitable Trust', 'class': 'OTHER'}, {'name': 'Tandem Diabetes Care, Inc.', 'class': 'INDUSTRY'}, {'name': 'DexCom, Inc.', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}