Ignite Creation Date:
2025-12-25 @ 2:36 AM
Ignite Modification Date:
2026-01-09 @ 3:08 PM
Study NCT ID:
NCT00574834
Status:
TERMINATED
Last Update Posted:
2019-09-12
First Post:
2007-12-13
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Mechanisms of Ramipril Reduction in the Onset of Type 2 Diabetes
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D024821', 'term': 'Metabolic Syndrome'}], 'ancestors': [{'id': 'D007333', 'term': 'Insulin Resistance'}, {'id': 'D006946', 'term': 'Hyperinsulinism'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D017257', 'term': 'Ramipril'}, {'id': 'D006852', 'term': 'Hydrochlorothiazide'}], 'ancestors': [{'id': 'D006574', 'term': 'Heterocyclic Compounds, 2-Ring'}, {'id': 'D000072471', 'term': 'Heterocyclic Compounds, Fused-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}, {'id': 'D002740', 'term': 'Chlorothiazide'}, {'id': 'D001581', 'term': 'Benzothiadiazines'}, {'id': 'D013449', 'term': 'Sulfonamides'}, {'id': 'D013450', 'term': 'Sulfones'}, {'id': 'D013457', 'term': 'Sulfur Compounds'}, {'id': 'D009930', 'term': 'Organic Chemicals'}, {'id': 'D049971', 'term': 'Thiazides'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'sdavis@medicine.umaryland.edu', 'phone': '410-328-2488', 'title': 'Stephen N. Davis, MBBS- Principal Investigator', 'organization': 'University of Maryland Baltimore'}, 'certainAgreement': {'otherDetails': 'Results of this trial were too preliminary to report. Trial was ended due to lack of funding to complete. No conclusions could be drawn from existing data.', 'restrictionType': 'OTHER', 'piSponsorEmployee': False, 'restrictiveAgreement': True}, 'limitationsAndCaveats': {'description': 'Early termination leading to small numbers of subjects analyzed. No conclusions drawn.'}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Ramipril', 'description': 'Patients randomized to 6 months treatment of Ramipril.\n\nRamipril: Ramipril 20 mg once daily for 6 months', 'otherNumAtRisk': 9, 'otherNumAffected': 0, 'seriousNumAtRisk': 9, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'HCTZ', 'description': 'Patients randomized to 6 months treatment of HCTZ.\n\nHCTZ-hydrochlorothiazide: HCTZ 25 mg once daily for 6 months', 'otherNumAtRisk': 4, 'otherNumAffected': 0, 'seriousNumAtRisk': 4, 'seriousNumAffected': 0}, {'id': 'EG002', 'title': 'Ramipril+HCTZ', 'description': 'Patients randomized to 6 months treatment of Ramipril+HCTZ.\n\nRamipril+HCTZ: Ramipril 20 mg and HCTZ 25 mg, both once daily for 6 months', 'otherNumAtRisk': 4, 'otherNumAffected': 0, 'seriousNumAtRisk': 4, 'seriousNumAffected': 0}], 'frequencyThreshold': '5'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Changes in Insulin Sensitivity', 'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'OG000'}, {'value': '4', 'groupId': 'OG001'}, {'value': '4', 'groupId': 'OG002'}]}], 'groups': [{'id': 'OG000', 'title': 'Ramipril', 'description': 'Patients randomized to 6 months treatment of Ramipril.\n\nRamipril: Ramipril 20 mg once daily for 6 months'}, {'id': 'OG001', 'title': 'HCTZ', 'description': 'Patients randomized to 6 months treatment of HCTZ.\n\nHCTZ-hydrochlorothiazide: HCTZ 25 mg once daily for 6 months'}, {'id': 'OG002', 'title': 'Ramipril+HCTZ', 'description': 'Patients randomized to 6 months treatment of Ramipril+HCTZ.\n\nRamipril+HCTZ: Ramipril 20 mg and HCTZ 25 mg, both once daily for 6 months'}], 'classes': [{'categories': [{'measurements': [{'value': '0.98', 'spread': '0.36', 'groupId': 'OG000'}, {'value': '1.5', 'spread': '0.23', 'groupId': 'OG001'}, {'value': '1.2', 'spread': '0.17', 'groupId': 'OG002'}]}]}], 'paramType': 'MEAN', 'timeFrame': '6 months', 'description': 'Measures of change in endogenous glucose production from baseline to final 30 minutes of clamp studies after 6 months of treatment.', 'unitOfMeasure': 'mg/kg/min', 'dispersionType': 'Standard Error', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Ramipril', 'description': 'Patients randomized to 6 months treatment of Ramipril.\n\nRamipril: Ramipril 20 mg once daily for 6 months'}, {'id': 'FG001', 'title': 'HCTZ', 'description': 'Patients randomized to 6 months treatment of HCTZ.\n\nHCTZ-hydrochlorothiazide: HCTZ 25 mg once daily for 6 months'}, {'id': 'FG002', 'title': 'Ramipril+HCTZ', 'description': 'Patients randomized to 6 months treatment of Ramipril+HCTZ.\n\nRamipril+HCTZ: Ramipril 20 mg and HCTZ 25 mg, both once daily for 6 months'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '4'}, {'groupId': 'FG002', 'numSubjects': '4'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '9'}, {'groupId': 'FG001', 'numSubjects': '4'}, {'groupId': 'FG002', 'numSubjects': '4'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}, {'groupId': 'FG002', 'numSubjects': '0'}]}]}], 'recruitmentDetails': 'Individuals with pre-diabetes (metabolic syndrome) are recruited for a 6 month study intervention.'}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '9', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}, {'value': '17', 'groupId': 'BG003'}]}], 'groups': [{'id': 'BG000', 'title': 'Ramipril', 'description': 'Patients randomized to 6 months treatment of Ramipril.\n\nRamipril: Ramipril 20 mg once daily for 6 months'}, {'id': 'BG001', 'title': 'HCTZ', 'description': 'Patients randomized to 6 months treatment of HCTZ.\n\nHCTZ-hydrochlorothiazide: HCTZ 25 mg once daily for 6 months'}, {'id': 'BG002', 'title': 'Ramipril+HCTZ', 'description': 'Patients randomized to 6 months treatment of Ramipril+HCTZ.\n\nRamipril+HCTZ: Ramipril 20 mg and HCTZ 25 mg, both once daily for 6 months'}, {'id': 'BG003', 'title': 'Total', 'description': 'Total of all reporting groups'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '9', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}, {'value': '17', 'groupId': 'BG003'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '49', 'spread': '8.5', 'groupId': 'BG000'}, {'value': '46', 'spread': '9', 'groupId': 'BG001'}, {'value': '41', 'spread': '13', 'groupId': 'BG002'}, {'value': '46', 'spread': '10', 'groupId': 'BG003'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}, {'value': '8', 'groupId': 'BG003'}]}, {'title': 'Male', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}, {'value': '9', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Race (NIH/OMB)', 'classes': [{'categories': [{'title': 'American Indian or Alaska Native', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}, {'title': 'Asian', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}, {'title': 'Native Hawaiian or Other Pacific Islander', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}, {'title': 'Black or African American', 'measurements': [{'value': '3', 'groupId': 'BG000'}, {'value': '1', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}, {'value': '6', 'groupId': 'BG003'}]}, {'title': 'White', 'measurements': [{'value': '6', 'groupId': 'BG000'}, {'value': '3', 'groupId': 'BG001'}, {'value': '2', 'groupId': 'BG002'}, {'value': '11', 'groupId': 'BG003'}]}, {'title': 'More than one race', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}, {'title': 'Unknown or Not Reported', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}, {'value': '0', 'groupId': 'BG003'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'United States', 'categories': [{'measurements': [{'value': '9', 'groupId': 'BG000'}, {'value': '4', 'groupId': 'BG001'}, {'value': '4', 'groupId': 'BG002'}, {'value': '17', 'groupId': 'BG003'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'phases': ['EARLY_PHASE1'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'DOUBLE', 'whoMasked': ['PARTICIPANT', 'INVESTIGATOR']}, 'primaryPurpose': 'PREVENTION', 'interventionModel': 'PARALLEL'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 17}}, 'statusModule': {'whyStopped': 'Lack of funding', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2007-03'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2019-09', 'completionDateStruct': {'date': '2014-08', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2019-09-10', 'studyFirstSubmitDate': '2007-12-13', 'resultsFirstSubmitDate': '2015-12-10', 'studyFirstSubmitQcDate': '2007-12-13', 'lastUpdatePostDateStruct': {'date': '2019-09-12', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2015-12-10', 'studyFirstPostDateStruct': {'date': '2007-12-17', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2016-01-15', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2014-08', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Changes in Insulin Sensitivity', 'timeFrame': '6 months', 'description': 'Measures of change in endogenous glucose production from baseline to final 30 minutes of clamp studies after 6 months of treatment.'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'conditions': ['Metabolic Syndrome']}, 'descriptionModule': {'briefSummary': "The study will be focused on determining the integrated in-vivo mechanisms responsible for Ramipril's effects on delaying type 2 diabetes and restoring normal (blood sugar levels) glycemia in patients with impaired glucose tolerance.\n\nHypothesis - Ramipril effects will delay the onset of type 2 diabetes and restore normal glycemia in patients with impaired glucose tolerance.", 'detailedDescription': "Several studies have demonstrated that therapeutic agents used to reduce glucose levels and/or weight can delay the onset of type 2 diabetes. Intriguingly, angiotensin converting enzyme (ACE) inhibitors or angiotensin receptor blockers (ARB) also result in reduction in the onset of type 2 DM. The most striking effect was found with Ramipril in the HOPE study. The onset of new type 2 DM was reduced by 34% (p\\<0.001) as compared to placebo. Furthermore, the results of the DREAM trial demonstrate that Ramipril at a dose of 15 mg can significantly reverse impaired glucose tolerance. However, the mechanisms underlying Ramipril effects to delay type 2 diabetes are not known.\n\nThe proposal will be focused on determining the integrated in-vivo mechanisms responsible for Ramipril's effects on delaying type 2 DM and restoring normal glycemia in patients with impaired glucose tolerance.\n\nThe specific aims of the project are:\n\n* to determine the effect of Ramipril on insulin resistance at the level of the liver and peripheral tissues,\n* to determine the effect of Ramipril on endothelial function,\n* to determine the effects of Ramipril on insulin secretion, and\n* to determine the effects of Ramipril on substrate flux, lipolysis and inflammatory cytokines."}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '65 Years', 'minimumAge': '20 Years', 'healthyVolunteers': True, 'eligibilityCriteria': 'Inclusion:\n\n* 48 (24 male / 24 female) with impaired glucose tolerance.\n* Impaired blood glucose values as outlined by the American Diabetes Association guideline. Fasting plasma glucose between 100 and 126 mg/dl or 2 hour post prandial glucose between 140 and 200 mg/dl\n* BMI \\> 25 kgM2\n* Age: 20-65 years\n* Treated or Untreated hypertension defined as measurement of seated BP at screening visit of systolic BP 120 to 150 and/ or diastolic BP 80 to 100.\n\nExclusion:\n\n* Patients receiving agents that can increase or lower blood glucose, i.e., metformin, thiazolidinediones, sulfonylureas, glitinides, acarbose, GLP-1 receptor agonists\n* Untreated or treated while seated Systolic Blood pressure \\>150and/or Diastolic Blood pressure \\>100\n* Taking hypertensive medications of HCTZ or ACE/ARB\n* Allergy to HCTZ, heparin, nitroglycerin or lidocaine\n* History of allergy or unacceptable side effects from ACE inhibitors\n* Pregnancy or intent to become pregnant during the study\n* Smoking\n* Subject unable to give voluntary informed consent\n\nPhysical Exam Exclusion Criteria\n\n* Clinically significant Cardiac Abnormalities (e.g. Heart Failure, Arrhythmia) from history or ECG in subjects \\> 40 years old\n* Pneumonia\n* Hepatic Failure/Jaundice\n* Renal Failure\n* Acute Cerebrovascular/ Neurological deficit\n* Fever greater than 38.0 C\n\nScreening Laboratory Tests Exclusion Criteria according to protocol'}, 'identificationModule': {'nctId': 'NCT00574834', 'briefTitle': 'Mechanisms of Ramipril Reduction in the Onset of Type 2 Diabetes', 'organization': {'class': 'OTHER', 'fullName': 'University of Maryland, Baltimore'}, 'officialTitle': 'Mechanisms of Reduced Ramipril on the Onset of Type 2 Diabetes Mellitis', 'orgStudyIdInfo': {'id': 'HP-00044872-Ramipril'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'ACTIVE_COMPARATOR', 'label': 'Ramipril', 'description': 'Patients randomized to 6 months treatment of Ramipril.', 'interventionNames': ['Drug: Ramipril']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'HCTZ', 'description': 'PAtients randomized to 6 months treatment of HCTZ.', 'interventionNames': ['Drug: HCTZ-hydrochlorothiazide']}, {'type': 'ACTIVE_COMPARATOR', 'label': 'Ramipril+HCTZ', 'description': 'Patients randomized to 6 months treatment of Ramipril+HCTZ.', 'interventionNames': ['Drug: Ramipril+HCTZ']}], 'interventions': [{'name': 'Ramipril', 'type': 'DRUG', 'otherNames': ['Altace'], 'description': 'Ramipril 20 mg once daily for 6 months', 'armGroupLabels': ['Ramipril']}, {'name': 'HCTZ-hydrochlorothiazide', 'type': 'DRUG', 'otherNames': ['Brand Names: HydroDIURIL, Microzide'], 'description': 'HCTZ 25 mg once daily for 6 months', 'armGroupLabels': ['HCTZ']}, {'name': 'Ramipril+HCTZ', 'type': 'DRUG', 'otherNames': ['Altace and HydroDIURIL, Microzide'], 'description': 'Ramipril 20 mg and HCTZ 25 mg, both once daily for 6 months', 'armGroupLabels': ['Ramipril+HCTZ']}]}, 'contactsLocationsModule': {'locations': [{'zip': '21201', 'city': 'Baltimore', 'state': 'Maryland', 'country': 'United States', 'facility': 'University of Maryland, Baltimore', 'geoPoint': {'lat': 39.29038, 'lon': -76.61219}}], 'overallOfficials': [{'name': 'Stephen N. Davis, MD, FRCP', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of Maryland, Baltimore'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of Maryland, Baltimore', 'class': 'OTHER'}, 'collaborators': [{'name': 'King Pharmaceuticals is now a wholly owned subsidiary of Pfizer', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'Professor', 'investigatorFullName': 'Stephen N. Davis, MBBS', 'investigatorAffiliation': 'University of Maryland, Baltimore'}}}}