Ignite Creation Date:
2025-12-25 @ 1:44 AM
Ignite Modification Date:
2025-12-26 @ 12:20 AM
Study NCT ID:
NCT01319994
Status:
COMPLETED
Last Update Posted:
2019-04-12
First Post:
2011-02-21
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Prevention of Metabolic Complications of Glucocorticoid Excess
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'interventionBrowseModule': {'meshes': [{'id': 'D008687', 'term': 'Metformin'}], 'ancestors': [{'id': 'D001645', 'term': 'Biguanides'}, {'id': 'D006146', 'term': 'Guanidines'}, {'id': 'D000578', 'term': 'Amidines'}, {'id': 'D009930', 'term': 'Organic Chemicals'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'm.korbonits@qmul.ac.uk', 'phone': '+442078826197', 'title': 'Prof M Korbonits', 'organization': 'Queen Mary University of London'}, 'certainAgreement': {'piSponsorEmployee': True}}, 'adverseEventsModule': {'timeFrame': '6 months', 'description': 'adverse event definition is matching the definition of clinicaltrials.org', 'eventGroups': [{'id': 'EG000', 'title': 'Metformin', 'description': 'Metformin 850mg TDS for 12 weeks', 'otherNumAtRisk': 26, 'otherNumAffected': 26, 'seriousNumAtRisk': 26, 'seriousNumAffected': 1}, {'id': 'EG001', 'title': 'Placebo', 'description': 'Placebo 850mg TDS for 12 weeks', 'otherNumAtRisk': 27, 'otherNumAffected': 22, 'seriousNumAtRisk': 27, 'seriousNumAffected': 9}], 'otherEvents': [{'term': 'Gastrointestinal side-effects', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numAffected': 16}, {'groupId': 'EG001', 'numAtRisk': 27, 'numAffected': 9}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'SNOMED CT'}, {'term': 'Other', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numAffected': 10}, {'groupId': 'EG001', 'numAtRisk': 27, 'numAffected': 18}], 'organSystem': 'General disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'SNOMED CT'}], 'seriousEvents': [{'term': 'Pneumonia', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 27, 'numAffected': 1}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'SNOMED CT'}, {'term': 'Ischaemic heart disease', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numAffected': 1}, {'groupId': 'EG001', 'numAtRisk': 27, 'numAffected': 0}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'SNOMED CT'}, {'term': 'Diverticulitis', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 27, 'numAffected': 1}], 'organSystem': 'Gastrointestinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'SNOMED CT'}, {'term': 'Atypical chest pain', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 27, 'numAffected': 1}], 'organSystem': 'Cardiac disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'SNOMED CT'}, {'term': "Raynaud's", 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 27, 'numAffected': 1}], 'organSystem': 'Vascular disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'SNOMED CT'}, {'term': 'Severe osmotic symptoms', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 27, 'numAffected': 2}], 'organSystem': 'Endocrine disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'SNOMED CT'}, {'term': 'Exacerbation of asthma', 'stats': [{'groupId': 'EG000', 'numAtRisk': 26, 'numAffected': 0}, {'groupId': 'EG001', 'numAtRisk': 27, 'numAffected': 3}], 'organSystem': 'Respiratory, thoracic and mediastinal disorders', 'assessmentType': 'SYSTEMATIC_ASSESSMENT', 'sourceVocabulary': 'SNOMED CT'}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'CT Abdomen', 'denoms': [{'units': 'Participants', 'counts': [{'value': '19', 'groupId': 'OG000'}, {'value': '21', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Metformin 850mg TDS'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo 850mg TDS'}], 'classes': [{'categories': [{'measurements': [{'value': '0.08', 'spread': '0.19', 'groupId': 'OG000'}, {'value': '-0.03', 'spread': '0.22', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': '3 months minus baseline', 'description': 'change in visceral/subcutaneous fat', 'unitOfMeasure': 'ratio', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'HOMA2-IR', 'denoms': [{'units': 'Participants', 'counts': [{'value': '19', 'groupId': 'OG000'}, {'value': '21', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Metformin', 'description': 'Metformin 850mg TDS'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo 850mg TDS'}], 'classes': [{'categories': [{'measurements': [{'value': '0.22', 'spread': '3.26', 'groupId': 'OG000'}, {'value': '2.35', 'spread': '3.23', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': '3 months minus baseline', 'description': 'The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta (β)-cell function. HOMA2-IR is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin resistance which is the reciprocal of insulin sensitivity (%S)(100/%S) as a percentage of a normal reference population (normal young adults). HOMA2-IR is calculated using the HOMA model: www.dtu.ox.ac.uk/homacalculator/', 'unitOfMeasure': 'HOMA score', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Metformin', 'description': 'Metformin 850mg TDS for 12 weeks'}, {'id': 'FG001', 'title': 'Placebo', 'description': 'Placebo 850mg TDS for 12 weeks'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '26'}, {'groupId': 'FG001', 'numSubjects': '27'}]}, {'type': 'Abto Keep Appoinment Shedule', 'achievements': [{'groupId': 'FG000', 'numSubjects': '23'}, {'groupId': 'FG001', 'numSubjects': '24'}]}, {'type': 'Tolerated at Least 1.7g/Day Dose', 'achievements': [{'groupId': 'FG000', 'numSubjects': '19'}, {'groupId': 'FG001', 'numSubjects': '24'}]}, {'type': 'Glucocorticoid Dose as Inc Cri', 'achievements': [{'groupId': 'FG000', 'numSubjects': '19'}, {'groupId': 'FG001', 'numSubjects': '22'}]}, {'type': 'Did Not Develop Overt Diabetes', 'achievements': [{'groupId': 'FG000', 'numSubjects': '19'}, {'groupId': 'FG001', 'numSubjects': '21'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '19'}, {'groupId': 'FG001', 'numSubjects': '21'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '7'}, {'groupId': 'FG001', 'numSubjects': '6'}]}], 'dropWithdraws': [{'type': 'Protocol Violation', 'reasons': [{'groupId': 'FG000', 'numSubjects': '7'}, {'groupId': 'FG001', 'numSubjects': '6'}]}]}], 'preAssignmentDetails': 'Patients were recruited into "Prevention" and "Treatment" algorithms initially. However, only the "Treatment" algorithm proved feasible for logistic reasons. Below are the results relating to patients randomized into the Treatment algorithm.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '26', 'groupId': 'BG000'}, {'value': '27', 'groupId': 'BG001'}, {'value': '53', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Metformin', 'description': 'Metformin 850mg TDS'}, {'id': 'BG001', 'title': 'Placebo', 'description': 'Placebo 850mg TDS'}, {'id': 'BG002', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '47', 'spread': '15', 'groupId': 'BG000'}, {'value': '45', 'spread': '15', 'groupId': 'BG001'}, {'value': '46', 'spread': '15', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '14', 'groupId': 'BG000'}, {'value': '15', 'groupId': 'BG001'}, {'value': '29', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '12', 'groupId': 'BG000'}, {'value': '12', 'groupId': 'BG001'}, {'value': '24', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Ethnicity (NIH/OMB)', 'classes': [{'categories': [{'title': 'Hispanic or Latino', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Not Hispanic or Latino', 'measurements': [{'value': '26', 'groupId': 'BG000'}, {'value': '27', 'groupId': 'BG001'}, {'value': '53', 'groupId': 'BG002'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'visceral to subcutanous fat ratio', 'classes': [{'categories': [{'measurements': [{'value': '0.44', 'groupId': 'BG000', 'lowerLimit': '0.33', 'upperLimit': '0.67'}, {'value': '0.58', 'groupId': 'BG001', 'lowerLimit': '0.34', 'upperLimit': '0.84'}, {'value': '0.50', 'groupId': 'BG002', 'lowerLimit': '0.33', 'upperLimit': '0.76'}]}]}], 'paramType': 'MEDIAN', 'description': 'Visceral to subcutaneous fat area ratio as assessed by CT at level L4', 'unitOfMeasure': 'ratio', 'dispersionType': 'INTER_QUARTILE_RANGE'}, {'title': 'HOMA2-IR', 'classes': [{'categories': [{'measurements': [{'value': '4.7', 'groupId': 'BG000', 'lowerLimit': '2.2', 'upperLimit': '5.5'}, {'value': '4.2', 'groupId': 'BG001', 'lowerLimit': '2.8', 'upperLimit': '5.4'}, {'value': '4.4', 'groupId': 'BG002', 'lowerLimit': '2.2', 'upperLimit': '5.3'}]}]}], 'paramType': 'MEDIAN', 'description': 'The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance using a HOMA model (https://www.dtu.ox.ac.uk/homacalculator/)', 'unitOfMeasure': 'HOMA score', 'dispersionType': 'INTER_QUARTILE_RANGE'}], 'populationDescription': 'Heterogeneous but well matched treatment groups'}}, 'protocolSection': {'designModule': {'phases': ['PHASE2', 'PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'TRIPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 57}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2012-07'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-01', 'completionDateStruct': {'date': '2015-01', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-01-14', 'studyFirstSubmitDate': '2011-02-21', 'resultsFirstSubmitDate': '2015-07-10', 'studyFirstSubmitQcDate': '2011-03-21', 'lastUpdatePostDateStruct': {'date': '2019-04-12', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2019-01-14', 'studyFirstPostDateStruct': {'date': '2011-03-22', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2019-04-12', 'type': 'ACTUAL'}, 'primaryCompletionDateStruct': {'date': '2014-08', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'CT Abdomen', 'timeFrame': '3 months minus baseline', 'description': 'change in visceral/subcutaneous fat'}], 'secondaryOutcomes': [{'measure': 'HOMA2-IR', 'timeFrame': '3 months minus baseline', 'description': 'The homeostatic model assessment (HOMA) is a method used to quantify insulin resistance and beta (β)-cell function. HOMA2-IR is a computer model that uses fasting plasma insulin and glucose concentrations to estimate insulin resistance which is the reciprocal of insulin sensitivity (%S)(100/%S) as a percentage of a normal reference population (normal young adults). HOMA2-IR is calculated using the HOMA model: www.dtu.ox.ac.uk/homacalculator/'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['glucocorticoid'], 'conditions': ['Iatrogenic Cushing Disease']}, 'referencesModule': {'references': [{'pmid': '32109422', 'type': 'DERIVED', 'citation': 'Pernicova I, Kelly S, Ajodha S, Sahdev A, Bestwick JP, Gabrovska P, Akanle O, Ajjan R, Kola B, Stadler M, Fraser W, Christ-Crain M, Grossman AB, Pitzalis C, Korbonits M. Metformin to reduce metabolic complications and inflammation in patients on systemic glucocorticoid therapy: a randomised, double-blind, placebo-controlled, proof-of-concept, phase 2 trial. Lancet Diabetes Endocrinol. 2020 Apr;8(4):278-291. doi: 10.1016/S2213-8587(20)30021-8. Epub 2020 Feb 25.'}]}, 'descriptionModule': {'briefSummary': 'According to current estimates, nearly 1% of the general population is treated with long-term glucocorticoids. Chronic hypercortisolism leads to a phenotype that resembles the metabolic syndrome. The investigators have shown that inhibition of adenosine-monophosphate-activated protein kinase (AMPK) activity in adipose tissue plays a role in corticosteroid-mediated insulin resistance. Metformin, one of the mainstay therapies for type 2 diabetes, is a known activator of AMPK, which mediates its beneficial effects on glucose and lipid metabolism. The investigators have shown in an animal model that metformin - via altering AMPK activity - prevents the development of the metabolic complications of glucocorticoid excess, and the investigators wish to confirm this in a human study. The aim of this prospective, randomised, double-blind, placebo-controlled study is to investigate the effect of metformin treatment on metabolic parameters in patients on long-term high-dose glucocorticoids. The study is part of the investigators translational project and could rapidly lead to immediate patient benefit, improving quality of life and reducing health care costs for the NHS.', 'detailedDescription': '2 Study Aims and Objectives To investigate the effect of metformin treatment on metabolic parameters in patients with long-term high dose GCs.\n\n3 Study Design 3.1 General Design We will recruit patients (18-75y) requiring glucocorticoid treatment for various inflammatory conditions (e.g. rheumatoid arthritis, giant cell arteritis/polymyalgia rheumatic, asthma, sarcoidosis) into a pilot, randomised, double-blind, placebo-controlled trial. These patients will be treated with metformin to prevent or reverse their metabolic complications. Prevention algorithm: Patients who are about to start GC treatment predictably for ≥12w at a ≥10mg/d prednisolone (or equivalent) dose who consent to participate in this study will be randomly assigned to receive either placebo (20 patients/group, see power calculations) or metformin at the maximum tolerated dose with a minimum of 850 mg bd for 12w. Treatment algorithm: Consenting patients already on long-term GC treatment (≥4w, ≥20mg/d prednisolone or equivalent) who are expected to continue for at least 12w at ≥10mg/d prednisolone will be randomly assigned to receive either placebo or metformin for 12w. In both algorithms, metformin treatment will be started gradually (as standard practice) to avoid gastrointestinal side effects and the full dose will be reached by day 10. Patients will have a full clinical assessment before the start of the metformin treatment and at the end of the 12w treatment period. Anthropometric and biochemical parameters and questionnaires will be repeated at 4 and 8 weeks.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '75 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* patients diagnosed with an inflammatory condition and not started yet on GC treatment or • patients with an inflammatory condition treated with GC \\>20mg/d of prednisolone (or its cumulative equivalent) for at least 4wks\n* minimal duration of prospective therapy 12w\n* dose of prednisolone ≥10mg/d (or equivalent GC)\n* ambulatory patients\n* patients \\>18 years old\n* ability to understand verbal and written instructions and informed consent\n\nExclusion Criteria:\n\n* prior therapy with metformin during the last 6 months\n* known pre-existing diabetes\n* pregnancy\n* breastfeeding\n* liver impairment: ALT and/or AST ≥2.5 x UNL\n* renal impairment: serum creatinine levels ≥135.0 µmol/L in males and ≥110.0 µmol/L in females\n* current malignancy\n* patients unable to give written informed consent\n* or patients not understanding English'}, 'identificationModule': {'nctId': 'NCT01319994', 'briefTitle': 'Prevention of Metabolic Complications of Glucocorticoid Excess', 'organization': {'class': 'OTHER', 'fullName': 'Barts & The London NHS Trust'}, 'officialTitle': 'Prevention of Metabolic Complications of Glucocorticoid Excess - a Randomised, Doubleblind,Placebo Controlled Study', 'orgStudyIdInfo': {'id': '09/H1102/82'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Metformin', 'description': 'Metformin 850mg TDS (12 weeks)', 'interventionNames': ['Drug: Metformin']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'description': 'Placebo 850mg TDS (12 weeks)', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Metformin', 'type': 'DRUG', 'otherNames': ['metformin tablet containing 850mg metformin'], 'description': 'Metformin 850mg TDS (12 weeks)', 'armGroupLabels': ['Metformin']}, {'name': 'Placebo', 'type': 'DRUG', 'otherNames': ['Placebo tablet matching the active drug tablet'], 'description': 'Placebo 850mg TDS (12 weeks)', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'city': 'London', 'country': 'United Kingdom', 'facility': 'Barts and the London', 'geoPoint': {'lat': 51.50853, 'lon': -0.12574}}], 'overallOfficials': [{'name': 'Marta Korbonits, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Barts and The London'}]}, 'ipdSharingStatementModule': {'ipdSharing': 'NO'}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Barts & The London NHS Trust', 'class': 'OTHER'}, 'collaborators': [{'name': 'Barts and the London School of Medicine and Dentistry', 'class': 'OTHER'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Marta Korbonits', 'investigatorAffiliation': 'Barts & The London NHS Trust'}}}}