Ignite Creation Date:
2025-12-24 @ 2:44 PM
Ignite Modification Date:
2026-04-16 @ 8:08 AM
Study NCT ID:
NCT01975259
Status:
COMPLETED
Last Update Posted:
2015-09-02
First Post:
2013-09-11
Is NOT Gene Therapy:
True
Has Adverse Events:
False
Brief Title:
Investigating the Incretin Effect in Cystic Fibrosis
Sponsor:
Organization:
Raw JSON
{'hasResults': False, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D003550', 'term': 'Cystic Fibrosis'}], 'ancestors': [{'id': 'D010182', 'term': 'Pancreatic Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D008171', 'term': 'Lung Diseases'}, {'id': 'D012140', 'term': 'Respiratory Tract Diseases'}, {'id': 'D030342', 'term': 'Genetic Diseases, Inborn'}, {'id': 'D009358', 'term': 'Congenital, Hereditary, and Neonatal Diseases and Abnormalities'}, {'id': 'D007232', 'term': 'Infant, Newborn, Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D005951', 'term': 'Glucose Tolerance Test'}, {'id': 'D052216', 'term': 'Glucagon-Like Peptide 1'}, {'id': 'D005749', 'term': 'Gastric Inhibitory Polypeptide'}, {'id': 'D000077330', 'term': 'Saline Solution'}, {'id': 'D000095583', 'term': 'Continuous Glucose Monitoring'}], 'ancestors': [{'id': 'D001774', 'term': 'Blood Chemical Analysis'}, {'id': 'D019963', 'term': 'Clinical Chemistry Tests'}, {'id': 'D019411', 'term': 'Clinical Laboratory Techniques'}, {'id': 'D019937', 'term': 'Diagnostic Techniques and Procedures'}, {'id': 'D003933', 'term': 'Diagnosis'}, {'id': 'D003940', 'term': 'Diagnostic Techniques, Endocrine'}, {'id': 'D008919', 'term': 'Investigative Techniques'}, {'id': 'D004763', 'term': 'Glucagon-Like Peptides'}, {'id': 'D052336', 'term': 'Proglucagon'}, {'id': 'D005768', 'term': 'Gastrointestinal Hormones'}, {'id': 'D006728', 'term': 'Hormones'}, {'id': 'D006730', 'term': 'Hormones, Hormone Substitutes, and Hormone Antagonists'}, {'id': 'D036361', 'term': 'Peptide Hormones'}, {'id': 'D009479', 'term': 'Neuropeptides'}, {'id': 'D010455', 'term': 'Peptides'}, {'id': 'D000602', 'term': 'Amino Acids, Peptides, and Proteins'}, {'id': 'D009419', 'term': 'Nerve Tissue Proteins'}, {'id': 'D011506', 'term': 'Proteins'}, {'id': 'D000077324', 'term': 'Crystalloid Solutions'}, {'id': 'D007552', 'term': 'Isotonic Solutions'}, {'id': 'D012996', 'term': 'Solutions'}, {'id': 'D004364', 'term': 'Pharmaceutical Preparations'}, {'id': 'D008991', 'term': 'Monitoring, Physiologic'}]}}, 'protocolSection': {'designModule': {'bioSpec': {'retention': 'SAMPLES_WITHOUT_DNA', 'description': 'Blood'}, 'studyType': 'OBSERVATIONAL', 'designInfo': {'timePerspective': 'PROSPECTIVE', 'observationalModel': 'CASE_CONTROL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 50}, 'patientRegistry': False}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-12'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2015-09', 'completionDateStruct': {'date': '2015-07', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2015-09-01', 'studyFirstSubmitDate': '2013-09-11', 'studyFirstSubmitQcDate': '2013-10-28', 'lastUpdatePostDateStruct': {'date': '2015-09-02', 'type': 'ESTIMATED'}, 'studyFirstPostDateStruct': {'date': '2013-11-04', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2015-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Area Under Curve (AUC) of Insulin & C-peptide secretion during a matched isoglycemic clamp', 'timeFrame': '4 hours', 'description': 'Differences in Insulin \\& C-peptide secretion will be measured over a 4-hour period following an oral glucose tolerance test and then separately over the same period during a matched isoglycemic glucose infusion (which will recreate the glucose values obtained during the oral glucose tolerance test). The difference in these values can be wholly attributed to the effect of incretin hormones.'}, {'measure': 'Volume of intravenous glucose required to maintain a hyperglycemic clamp at 180-216mg/dL', 'timeFrame': '3 hours', 'description': 'A hyperglycemic clamp uses an intravenous glucose infusion to fix blood sugar at a certain level. We will use such a technique to fix blood sugar levels at 180-216mg/dL (10-12 mmol/l) for one hour then infuse either an incretin hormone (GLP-1/GIP) or placebo (sodium chloride) for a further two hours. The excess volume of intravenous glucose required during the last two hours of the test (compared to the first) will allow us to calculate what if any effect the incretin hormones have on the pancreas in patients with Cystic Fibrosis'}], 'secondaryOutcomes': [{'measure': 'Serum DPP-4 levels', 'timeFrame': '0 mins', 'description': 'We will measure serum DPP-4 levels on 2 separate occasions in both CF and control groups to establish if there are any differences in how rapidly the incretin hormones are deactivated between the groups'}, {'measure': 'AUC incretin hormone levels (GLP-1/GIP)', 'timeFrame': '4 hours', 'description': 'Incretin hormone levels (GLP-1/GIP) will be measured in response to an oral glucose tolerance test, an intravenous isoglycemic glucose infusion as well as in response to standardised meals of different composition (fat-rich, carbohydrate rich \\& mixed).'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'conditions': ['Cystic Fibrosis']}, 'referencesModule': {'references': [{'pmid': '3514343', 'type': 'BACKGROUND', 'citation': 'Nauck M, Stockmann F, Ebert R, Creutzfeldt W. Reduced incretin effect in type 2 (non-insulin-dependent) diabetes. Diabetologia. 1986 Jan;29(1):46-52. doi: 10.1007/BF02427280.'}, {'pmid': '8423228', 'type': 'BACKGROUND', 'citation': 'Nauck MA, Heimesaat MM, Orskov C, Holst JJ, Ebert R, Creutzfeldt W. Preserved incretin activity of glucagon-like peptide 1 [7-36 amide] but not of synthetic human gastric inhibitory polypeptide in patients with type-2 diabetes mellitus. J Clin Invest. 1993 Jan;91(1):301-7. doi: 10.1172/JCI116186.'}, {'pmid': '19538232', 'type': 'BACKGROUND', 'citation': 'Mohan K, Miller H, Dyce P, Grainger R, Hughes R, Vora J, Ledson M, Walshaw M. Mechanisms of glucose intolerance in cystic fibrosis. Diabet Med. 2009 Jun;26(6):582-8. doi: 10.1111/j.1464-5491.2009.02738.x.'}, {'pmid': '10988101', 'type': 'BACKGROUND', 'citation': 'Milla CE, Warwick WJ, Moran A. Trends in pulmonary function in patients with cystic fibrosis correlate with the degree of glucose intolerance at baseline. Am J Respir Crit Care Med. 2000 Sep;162(3 Pt 1):891-5. doi: 10.1164/ajrccm.162.3.9904075.'}, {'pmid': '19910502', 'type': 'BACKGROUND', 'citation': 'Hameed S, Morton JR, Jaffe A, Field PI, Belessis Y, Yoong T, Katz T, Verge CF. Early glucose abnormalities in cystic fibrosis are preceded by poor weight gain. Diabetes Care. 2010 Feb;33(2):221-6. doi: 10.2337/dc09-1492. Epub 2009 Nov 12.'}, {'pmid': '12766139', 'type': 'BACKGROUND', 'citation': 'Dobson L, Sheldon CD, Hattersley AT. Validation of interstitial fluid continuous glucose monitoring in cystic fibrosis. Diabetes Care. 2003 Jun;26(6):1940-1. doi: 10.2337/diacare.26.6.1940-a. No abstract available.'}, {'pmid': '17409029', 'type': 'BACKGROUND', 'citation': 'Costa M, Potvin S, Hammana I, Malet A, Berthiaume Y, Jeanneret A, Lavoie A, Levesque R, Perrier J, Poisson D, Karelis AD, Chiasson JL, Rabasa-Lhoret R. Increased glucose excursion in cystic fibrosis and its association with a worse clinical status. J Cyst Fibros. 2007 Nov 30;6(6):376-83. doi: 10.1016/j.jcf.2007.02.005. Epub 2007 Apr 3.'}, {'pmid': '22138561', 'type': 'BACKGROUND', 'citation': 'Hillman M, Eriksson L, Mared L, Helgesson K, Landin-Olsson M. Reduced levels of active GLP-1 in patients with cystic fibrosis with and without diabetes mellitus. J Cyst Fibros. 2012 Mar;11(2):144-9. doi: 10.1016/j.jcf.2011.11.001. Epub 2011 Dec 3.'}, {'pmid': '21448848', 'type': 'BACKGROUND', 'citation': 'Anzeneder L, Kircher F, Feghelm N, Fischer R, Seissler J. Kinetics of insulin secretion and glucose intolerance in adult patients with cystic fibrosis. Horm Metab Res. 2011 May;43(5):355-60. doi: 10.1055/s-0031-1275270. Epub 2011 Mar 29.'}, {'pmid': '8480468', 'type': 'BACKGROUND', 'citation': 'Lanng S, Thorsteinsson B, Roder ME, Orskov C, Holst JJ, Nerup J, Koch C. Pancreas and gut hormone responses to oral glucose and intravenous glucagon in cystic fibrosis patients with normal, impaired, and diabetic glucose tolerance. Acta Endocrinol (Copenh). 1993 Mar;128(3):207-14. doi: 10.1530/acta.0.1280207.'}]}, 'descriptionModule': {'briefSummary': 'Most Cystic fibrosis (CF) patients now commonly live well into adulthood, this means they are progressively accumulating damage to the insulin-secreting cells inside their pancreas. This explains why most adult patients have some degree of abnormal sugar regulation \\& rates of diabetes rise significantly with age. CF related diabetes is categorically different from other types of diabetes \\& its development is serious as it heralds a faster decline in lung function \\& a reduced life expectancy.\n\nThe hallmark of abnormal sugar handling in CF is high glucose levels after meals as the damaged pancreas responds abnormally slowly. Over 70% of the initial response of a healthy pancreas is induced, not by glucose alone, but by hormones released from the bowel known as incretins. We want to establish whether incretins are important in blood sugar handling in CF as specific drugs that enhance their effect are now available.\n\nThe study hypothesis is that the incretin system will function normally in patients with Cystic Fibrosis. To show this we will measure how much insulin secretion is dependant on incretin hormones in CF patients by comparing levels after a sugary drink test and then an intravenous glucose drip test (run at a rate that mimics the blood sugar levels obtained during the first test to make it a fair comparison ) - as incretins will only be produced in the first test when the sugar passes through the bowel any extra insulin produced will be due to these hormones. To detect resistance to the incretin hormones we will separately measure responses to direct infusions of the hormones themselves. We will explore which components of meals cause incretin hormone release from the bowel wall by measuring blood levels after different types of meals are consumed. Finally we will measure levels of the enzyme that breaks down the incretin hormones (DPP-4) to know if they are deactivated more quickly in people with CF. By describing the incretin system in CF we will considerably improve our understanding of this important condition as well as potentially highlighting new ways to treat it.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['CHILD', 'ADULT'], 'maximumAge': '50 Years', 'minimumAge': '17 Years', 'samplingMethod': 'NON_PROBABILITY_SAMPLE', 'studyPopulation': 'The CF Cohort will be recruited from the population of Patients attending Adult CF Service at Liverpool Heart \\& Chest Hospital, Liverpool, United Kingdom\n\nThe control group will be invited to participate from the general public. We will advertise our study through the Liverpool Heart \\& Chest Hospital and also via GP surgeries (Primary care clinics) in both electronic \\& paper forms.', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Cystic fibrosis as diagnosed by EITHER Cystic fibrosis transmembrane conductance regulator (CFTR) mutation on genotyping OR Positive sweat test (Chloride ≥60mmol/L after pilocarpine iontophoresis) AND Clinical features in keeping with a diagnosis of Cystic Fibrosis\n* Clinically stable for at least 4 weeks without inpatient or outpatient treatment for an infective exacerbation - including antibiotics (other than long-term prophylactic therapy) or steroids\n\nExclusion Criteria:\n\n* Active Pregnancy or \\<12 months Post-partum\n* Clinically unstable patients\n* Patients on long-term steroids\n* Patients with known gastroparesis or previous surgery to the gastrointestinal tract (including vagotomy)\n* History of organ transplant or planned organ transplant awaited\n* Non-CF related diabetes (e.g. Type 1 or 2 Diabetes Mellitus)\n* Active malignancy\n* Clinically significant derangements in haematological or biochemical indices\n* Clinical symptoms of malabsorption (frequent bowel motions/passing of undigested foodstuffs or steatorrhoea)\n* Known difficult venous access\n* Use of bile acid sequestrants in the previous 4 weeks'}, 'identificationModule': {'nctId': 'NCT01975259', 'acronym': 'IECF', 'briefTitle': 'Investigating the Incretin Effect in Cystic Fibrosis', 'organization': {'class': 'OTHER', 'fullName': 'Liverpool Heart and Chest Hospital NHS Foundation Trust'}, 'officialTitle': 'Investigating the Incretin Effect in Cystic Fibrosis', 'orgStudyIdInfo': {'id': '1004'}, 'secondaryIdInfos': [{'id': '2013-003758-26', 'type': 'EUDRACT_NUMBER'}]}, 'armsInterventionsModule': {'armGroups': [{'label': 'Cystic Fibrosis', 'description': 'Adult patients with confirmed cystic fibrosis who are clinically stable. Interventions:\n\nOral Glucose Tolerance test (75g 2-hour) Modified Oral Glucose Tolerance Test (50g 4-hours) Matched isoglycemic clamp Hyperglycemic clamp with concurrent GLP-1 infusion Hyperglycemic Clamp with concurrent GIP infusion Hyperglycemic clamp with placebo infusion Liquid Meal Test (Carbohydrate-rich) Continuous Glucose Monitoring', 'interventionNames': ['Drug: Oral Glucose Tolerance test (75g 2-hour)', 'Drug: Modified Oral Glucose Tolerance Test (50g 4-hours)', 'Drug: Matched isoglycemic clamp', 'Drug: Hyperglycemic clamp with concurrent GLP-1 infusion', 'Drug: Hyperglycemic Clamp with concurrent GIP infusion', 'Drug: Hyperglycemic clamp with placebo infusion', 'Other: Liquid Meal Test (Carbohydrate-rich)', 'Other: Liquid Meal Test (Fat-rich)', 'Other: Liquid Meal Test (Mixed)', 'Device: Continuous Glucose Monitoring']}, {'label': 'Controls', 'description': 'Adult Non-CF subjects matched for age and body mass index with normal glucose tolerance.\n\nOral Glucose Tolerance test (75g 2-hour) Modified Oral Glucose Tolerance Test (50g 4-hours) Matched isoglycemic clamp Hyperglycemic clamp with concurrent GLP-1 infusion Hyperglycemic Clamp with concurrent GIP infusion Hyperglycemic clamp with placebo infusion Liquid Meal Test (Carbohydrate-rich)', 'interventionNames': ['Drug: Oral Glucose Tolerance test (75g 2-hour)', 'Drug: Modified Oral Glucose Tolerance Test (50g 4-hours)', 'Drug: Matched isoglycemic clamp', 'Drug: Hyperglycemic clamp with concurrent GLP-1 infusion', 'Drug: Hyperglycemic Clamp with concurrent GIP infusion', 'Drug: Hyperglycemic clamp with placebo infusion', 'Other: Liquid Meal Test (Carbohydrate-rich)', 'Other: Liquid Meal Test (Fat-rich)', 'Other: Liquid Meal Test (Mixed)']}], 'interventions': [{'name': 'Oral Glucose Tolerance test (75g 2-hour)', 'type': 'DRUG', 'otherNames': ['OGTT'], 'description': 'A standard 2-hour oral glucose tolerance test where fasted patients (10hours overnight) consume a 75g glucose solution \\& have glucose levels recorded up to every 30 mins for 2hours', 'armGroupLabels': ['Controls', 'Cystic Fibrosis']}, {'name': 'Modified Oral Glucose Tolerance Test (50g 4-hours)', 'type': 'DRUG', 'otherNames': ['Modified OGTT', '50g OGTT'], 'description': 'A 4-hour version of the oral glucose tolerance test where fasted patients (10hours overnight) consume a 50g of glucose solution \\& have glucose levels recorded up to every 5mins as well pancreatic and incretin responses at 10 fixed time points.', 'armGroupLabels': ['Controls', 'Cystic Fibrosis']}, {'name': 'Matched isoglycemic clamp', 'type': 'DRUG', 'otherNames': ['isoglycemic clamp'], 'description': 'A glucose drip will be infused at a variable rate that recreates the individual subjects blood glucose values obtained during their 4-hour modified oral glucose tolerance test. This test will therefore last 4-hours and again subjects will be fasted (10hours overnight) at the time of the test. The same blood tests will be performed at the same time points as the modified glucose tolerance test', 'armGroupLabels': ['Controls', 'Cystic Fibrosis']}, {'name': 'Hyperglycemic clamp with concurrent GLP-1 infusion', 'type': 'DRUG', 'otherNames': ['Glucagon-like peptide-1'], 'description': 'An intravenous glucose infusion will be infused at a rate that maintains blood glucose at a level of 180-216mg/dL (10-12 mmol/l) (hyperglycemic clamp). After 60mins an infusion of GLP-1 will be commenced at a rate of 0.25pmol/kg/min for 60mins and then continued at a rate of 1.2pmol/kg/min for a further 60mins. Subjects will be blinded to what infusion they are receiving.', 'armGroupLabels': ['Controls', 'Cystic Fibrosis']}, {'name': 'Hyperglycemic Clamp with concurrent GIP infusion', 'type': 'DRUG', 'otherNames': ['gastric inhibitory polypeptide', 'glucose-dependent insulinotropic peptide'], 'description': 'An intravenous glucose infusion will be infused at a rate that maintains blood glucose at a level of 180-216mg/dL (10-12 mmol/l) (hyperglycemic clamp). After 60mins an infusion of GIP will be commenced at a rate of 1pmol/kg/min for 60mins and then continued at a rate of 4pmol/kg/min for a further 60mins. Subjects will be blinded to what infusion they are receiving.', 'armGroupLabels': ['Controls', 'Cystic Fibrosis']}, {'name': 'Hyperglycemic clamp with placebo infusion', 'type': 'DRUG', 'otherNames': ['Hyperglycemic clamp with normal saline (0.9%) infusion'], 'description': 'An intravenous glucose infusion will be infused at a rate that maintains blood glucose at a level of 180-216mg/dL (10-12 mmol/l) (hyperglycemic clamp).\n\nAfter 60mins an infusion of normal saline will be commenced as a placebo infusion. It will be infused at a rate so that the total volume of fluid is similar to that infused during the other two hyperglycemic clamp interventions. Subjects will be blinded to what infusion they are receiving.', 'armGroupLabels': ['Controls', 'Cystic Fibrosis']}, {'name': 'Liquid Meal Test (Carbohydrate-rich)', 'type': 'OTHER', 'description': 'A standardised liquid meal (carbohydrate-rich) containing approximately 500kcal would be administered to patients who had fasted overnight (10hrs). Over the next 4hours bloods would be sampled at 10 fixed time points to measure features of the incretin response to this type of meal.', 'armGroupLabels': ['Controls', 'Cystic Fibrosis']}, {'name': 'Liquid Meal Test (Fat-rich)', 'type': 'OTHER', 'description': 'A standardised liquid meal (fat-rich) containing approximately 500kcal would be administered to patients who had fasted overnight (10hrs). Over the next 4hours bloods would be sampled at 10 fixed time points to measure features of the incretin response to this type of meal.', 'armGroupLabels': ['Controls', 'Cystic Fibrosis']}, {'name': 'Liquid Meal Test (Mixed)', 'type': 'OTHER', 'description': 'A standardised liquid meal (mixed) containing approximately 500kcal would be administered to patients who had fasted overnight (10hrs). Over the next 4hours bloods would be sampled at 10 fixed time points to measure features of the incretin response to this type of meal.', 'armGroupLabels': ['Controls', 'Cystic Fibrosis']}, {'name': 'Continuous Glucose Monitoring', 'type': 'DEVICE', 'otherNames': ['CGM', 'CGMS'], 'description': 'Continuous glucose monitoring entails wearing a small portable device, usually on the upper arm, for a period of three days. The device uses a small plastic tube to record the glucose level from interstitial fluid \\& every minute wirelessly transmits this information to a base unit to enable a very accurate estimate of average blood sugar control to be defined.', 'armGroupLabels': ['Cystic Fibrosis']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'L14 3PE', 'city': 'Liverpool', 'country': 'United Kingdom', 'facility': 'Liverpool Heart and Chest Hospital', 'geoPoint': {'lat': 53.41058, 'lon': -2.97794}}], 'overallOfficials': [{'name': 'Gareth H Jones, MBChB', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Liverpool Heart and Chest Hospital'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Liverpool Heart and Chest Hospital NHS Foundation Trust', 'class': 'OTHER'}, 'responsibleParty': {'type': 'SPONSOR'}}}}