Ignite Creation Date:
2025-12-24 @ 5:28 PM
Ignite Modification Date:
2026-03-23 @ 10:47 PM
Study NCT ID:
NCT01849068
Status:
COMPLETED
Last Update Posted:
2016-04-12
First Post:
2013-05-06
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Effects of Selective Inhibition of Cholesterol Absorption With Ezetimibe on Intestinal Cholesterol Homeostasis in Dyslipidemic Men With Insulin-resistance - a Pilot Study
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': 'D000069438', 'term': 'Ezetimibe'}], 'ancestors': [{'id': 'D001384', 'term': 'Azetidines'}, {'id': 'D001385', 'term': 'Azetines'}, {'id': 'D006573', 'term': 'Heterocyclic Compounds, 1-Ring'}, {'id': 'D006571', 'term': 'Heterocyclic Compounds'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'patrick.couture@crchul.ulaval.ca', 'phone': '418-654-2106', 'title': 'Dr. Patrick Couture MD, PhD, FRCP', 'organization': 'Laval University'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Ezetimibe', 'description': 'Ezetimibe 10 mg/d for 12 weeks Ezetimibe 10 mg/d for 12 weeks', 'otherNumAtRisk': 20, 'otherNumAffected': 0, 'seriousNumAtRisk': 20, 'seriousNumAffected': 0}, {'id': 'EG001', 'title': 'Placebo', 'description': 'Placebo for 12 weeks Placebo for 12 weeks', 'otherNumAtRisk': 20, 'otherNumAffected': 0, 'seriousNumAtRisk': 20, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Change in Intestinal mRNA Expression Levels of LDL Receptor Between the Two 12-week Interventions', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ezetimibe', 'description': 'Ezetimibe: Ezetimibe 10 mg/d for 12 weeks Ezetimibe 10 mg/d for 12 weeks'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo: Placebo for 12 weeks Placebo for 12 weeks'}], 'classes': [{'categories': [{'measurements': [{'value': '110531', 'spread': '32604', 'groupId': 'OG000'}, {'value': '95140', 'spread': '31840', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'At the end of the two 12-week interventions (Week 12 and 24)', 'description': 'We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation).\n\nWe combined the results at the end of each placebo phase from both sequence (average and standard deviation).', 'unitOfMeasure': '#copies/100000 copies housekeeping gene', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Intestinal mRNA Expression Levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA Reductase Between the Two 12-week Interventions', 'denoms': [{'units': 'Participants', 'counts': [{'value': '20', 'groupId': 'OG000'}, {'value': '20', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ezetimibe', 'description': 'Ezetimibe: Ezetimibe 10 mg/d for 12 weeks Ezetimibe 10 mg/d for 12 weeks'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo: Placebo for 12 weeks Placebo for 12 weeks'}], 'classes': [{'title': 'HMGCoA reductase', 'categories': [{'measurements': [{'value': '354911', 'spread': '102607', 'groupId': 'OG000'}, {'value': '311268', 'spread': '88237', 'groupId': 'OG001'}]}]}, {'title': 'PCSK9', 'categories': [{'measurements': [{'value': '9079', 'spread': '5816', 'groupId': 'OG000'}, {'value': '8091', 'spread': '6131', 'groupId': 'OG001'}]}]}, {'title': 'SREBP-2', 'categories': [{'measurements': [{'value': '193012', 'spread': '32787', 'groupId': 'OG000'}, {'value': '182349', 'spread': '36681', 'groupId': 'OG001'}]}]}, {'title': 'NPC1L1', 'categories': [{'measurements': [{'value': '454298', 'spread': '97707', 'groupId': 'OG000'}, {'value': '448686', 'spread': '138746', 'groupId': 'OG001'}]}]}, {'title': 'ABCG5', 'categories': [{'measurements': [{'value': '271811', 'spread': '111688', 'groupId': 'OG000'}, {'value': '283863', 'spread': '132434', 'groupId': 'OG001'}]}]}, {'title': 'ABCG8', 'categories': [{'measurements': [{'value': '125315', 'spread': '46842', 'groupId': 'OG000'}, {'value': '129551', 'spread': '63246', 'groupId': 'OG001'}]}]}], 'paramType': 'MEAN', 'timeFrame': 'At the end of the two 12-week interventions (Week 12 and 24)', 'description': 'We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation).\n\nWe combined the results at the end of each placebo phase from both sequence (average and standard deviation).', 'unitOfMeasure': '#copies/100000 copies housekeeping gene', 'dispersionType': 'Standard Deviation', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Change in Intestinal Protein Levels of LDL Receptor Between the Two 12-week Interventions', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ezetimibe', 'description': 'Ezetimibe: Ezetimibe 10 mg/d for 12 weeks Ezetimibe 10 mg/d for 12 weeks'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo: Placebo for 12 weeks Placebo for 12 weeks'}], 'timeFrame': 'At the end of the two 12-week interventions (Week 12 and 24)', 'description': 'We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation).\n\nWe combined the results at the end of each placebo phase from both sequence (average and standard deviation).', 'reportingStatus': 'POSTED', 'populationDescription': 'Data will never be analyzed because the mRNA expression of LDL receptor is sufficient.'}, {'type': 'SECONDARY', 'title': 'Change in Protein Levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA Reductase Between the Two 12-week Interventions', 'denoms': [{'units': 'Participants', 'counts': [{'value': '0', 'groupId': 'OG000'}, {'value': '0', 'groupId': 'OG001'}]}], 'groups': [{'id': 'OG000', 'title': 'Ezetimibe', 'description': 'Ezetimibe: Ezetimibe 10 mg/d for 12 weeks Ezetimibe 10 mg/d for 12 weeks'}, {'id': 'OG001', 'title': 'Placebo', 'description': 'Placebo: Placebo for 12 weeks Placebo for 12 weeks'}], 'timeFrame': 'At the end of the two 12-week interventions (Week 12 and 24)', 'description': 'We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation).\n\nWe combined the results at the end of each placebo phase from both sequence (average and standard deviation).', 'reportingStatus': 'POSTED', 'populationDescription': 'Data will never be analyzed because the mRNA expression of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA reductase are sufficient.'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Ezetimibe First, Then Placebo', 'description': 'First intervention: Ezetimibe 10 mg/d for 12 weeks Second intervention: Placebo for 12 weeks'}, {'id': 'FG001', 'title': 'Placebo First, Then Ezetimibe', 'description': 'First intervention: Placebo for 12 weeks Second intervention: Ezetimibe 10 mg/d for 12 weeks'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}, {'groupId': 'FG001', 'numSubjects': '10'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '10'}, {'groupId': 'FG001', 'numSubjects': '10'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}, {'groupId': 'FG001', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '10', 'groupId': 'BG000'}, {'value': '10', 'groupId': 'BG001'}, {'value': '20', 'groupId': 'BG002'}]}], 'groups': [{'id': 'BG000', 'title': 'Ezetimibe First Then Placebo', 'description': 'First intervention: Ezetimibe 10 mg/d for 12 weeks Second intervention: Placebo 12 weeks'}, {'id': 'BG001', 'title': 'Placebo First Then Ezetimibe', 'description': 'First intervention: Placebo for 12 weeks Second intervention: Ezetimibe 12 weeks'}, {'id': 'BG002', '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'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '10', 'groupId': 'BG000'}, {'value': '10', 'groupId': 'BG001'}, {'value': '20', 'groupId': 'BG002'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Age, Continuous', 'classes': [{'categories': [{'measurements': [{'value': '39.4', 'spread': '7.9', 'groupId': 'BG000'}, {'value': '39.4', 'spread': '13.6', 'groupId': 'BG001'}, {'value': '39.4', 'spread': '10.8', 'groupId': 'BG002'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'years', 'dispersionType': 'STANDARD_DEVIATION'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '0', 'groupId': 'BG000'}, {'value': '0', 'groupId': 'BG001'}, {'value': '0', 'groupId': 'BG002'}]}, {'title': 'Male', 'measurements': [{'value': '10', 'groupId': 'BG000'}, {'value': '10', 'groupId': 'BG001'}, {'value': '20', 'groupId': 'BG002'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Region of Enrollment', 'classes': [{'title': 'Canada', 'categories': [{'measurements': [{'value': '10', 'groupId': 'BG000'}, {'value': '10', 'groupId': 'BG001'}, {'value': '20', 'groupId': 'BG002'}]}]}], 'paramType': 'NUMBER', 'unitOfMeasure': 'participants'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE3'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'RANDOMIZED', 'maskingInfo': {'masking': 'QUADRUPLE', 'whoMasked': ['PARTICIPANT', 'CARE_PROVIDER', 'INVESTIGATOR', 'OUTCOMES_ASSESSOR']}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'CROSSOVER'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 20}}, 'statusModule': {'overallStatus': 'COMPLETED', 'startDateStruct': {'date': '2013-06'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2016-03', 'completionDateStruct': {'date': '2016-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2016-03-14', 'studyFirstSubmitDate': '2013-05-06', 'resultsFirstSubmitDate': '2016-02-15', 'studyFirstSubmitQcDate': '2013-05-06', 'lastUpdatePostDateStruct': {'date': '2016-04-12', 'type': 'ESTIMATED'}, 'resultsFirstSubmitQcDate': '2016-03-14', 'studyFirstPostDateStruct': {'date': '2013-05-08', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2016-04-12', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2015-06', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Change in Intestinal mRNA Expression Levels of LDL Receptor Between the Two 12-week Interventions', 'timeFrame': 'At the end of the two 12-week interventions (Week 12 and 24)', 'description': 'We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation).\n\nWe combined the results at the end of each placebo phase from both sequence (average and standard deviation).'}], 'secondaryOutcomes': [{'measure': 'Change in Intestinal mRNA Expression Levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA Reductase Between the Two 12-week Interventions', 'timeFrame': 'At the end of the two 12-week interventions (Week 12 and 24)', 'description': 'We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation).\n\nWe combined the results at the end of each placebo phase from both sequence (average and standard deviation).'}, {'measure': 'Change in Intestinal Protein Levels of LDL Receptor Between the Two 12-week Interventions', 'timeFrame': 'At the end of the two 12-week interventions (Week 12 and 24)', 'description': 'We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation).\n\nWe combined the results at the end of each placebo phase from both sequence (average and standard deviation).'}, {'measure': 'Change in Protein Levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA Reductase Between the Two 12-week Interventions', 'timeFrame': 'At the end of the two 12-week interventions (Week 12 and 24)', 'description': 'We combined the results at the end of each ezetimibe phase from both sequence (average and standard deviation).\n\nWe combined the results at the end of each placebo phase from both sequence (average and standard deviation).'}]}, 'oversightModule': {'oversightHasDmc': False}, 'conditionsModule': {'conditions': ['Metabolic Syndrome X']}, 'descriptionModule': {'briefSummary': 'Ezetimibe has been shown to inhibit cholesterol absorption and several lines of evidence from in vitro systems and animal models suggest that this effect is associated with an increase in low-density lipoprotein (LDL) receptor expression in the small intestine. The impact of a treatment with ezetimibe on intestinal gene expression and protein mass levels of LDL receptor and other key genes involved in intestinal cholesterol homeostasis will be examined in dyslipidemic men with insulin-resistance. In the present study, gene expression studies and protein mass levels will be assessed on duodenal biopsies by real-time polymerase chain reaction (rt-PCR) and liquid chromatography-mass spectrometry (LC-MS/MS), respectively. The primary objective of this proposal is to examine the effects of ezetimibe on intestinal gene expression (rt-PCR) and protein mass levels (LC-MS/MS) of LDL receptor in dyslipidemic men with insulin-resistance. The secondary objective is to examine the impact of ezetimibe treatment on intestinal gene expression and protein mass levels of sterol regulatory element-binding protein (SREBP)-2, Niemann-Pick C1-Like1 (NPC1L1), ATP binding cassette gene (ABCG)-5/8, proprotein convertase subtilisin/kexin type 9 (PCSK9) and 3-hydroxy-3-methyl-glutaryl-CoA (HMG CoA) reductase.\n\nPrimary hypothesis Treatment with ezetimibe 10 mg/day will significantly increase duodenal mRNA and protein mass levels of LDL receptor in dyslipidemic men with insulin-resistance.\n\nSecondary hypothesis Treatment with ezetimibe 10 mg/day will significantly increase duodenal mRNA and protein mass levels of SREBP-2, NPC1L1, ABCG5/8, PCSK9 and HMG CoA reductase in dyslipidemic men with insulin-resistance.'}, 'eligibilityModule': {'sex': 'MALE', 'stdAges': ['ADULT'], 'maximumAge': '60 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': 'Inclusion Criteria:\n\n* Men aged between 18-60 years\n* Waist circumference \\> 102 cm\n* HDL-cholesterol \\< 1.1 mmol/L\n* Triglycerides \\> 1.7 mmol/L\n* Fasting blood glucose \\> 6.1 mmol/L\n* Normal blood pressure (\\<130/85)\n\nExclusion Criteria:\n\n* Women\n* Men \\< 18 or \\> 60 years\n* Smokers (\\> 1 cigarette/day)\n* Body weight variation \\> 10% during the last 6 months prior to the study baseline\n* Subjects with a previous history of cardiovascular disease\n* Subjects with type 2 diabetes\n* Subjects with a monogenic dyslipidemia\n* Subjects on hypertension medications or medications known to affect lipoprotein metabolism or the integrity of gastrointestinal mucosa\n* Subjects with endocrine or gastrointestinal disorders\n* History of alcohol or drug abuse within the past 2 years\n* Subjects who are in a situation or have any condition that, in the opinion of the investigator, may interfere with optimal participation in the study.'}, 'identificationModule': {'nctId': 'NCT01849068', 'acronym': 'EZEmRNA', 'briefTitle': 'Effects of Selective Inhibition of Cholesterol Absorption With Ezetimibe on Intestinal Cholesterol Homeostasis in Dyslipidemic Men With Insulin-resistance - a Pilot Study', 'organization': {'class': 'OTHER', 'fullName': 'Laval University'}, 'officialTitle': 'Effects of Selective Inhibition of Cholesterol Absorption With Ezetimibe on Intestinal Cholesterol Homeostasis in Dyslipidemic Men With Insulin-resistance - a Pilot Study', 'orgStudyIdInfo': {'id': 'INAF-B13-04-1195'}}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Ezetimibe', 'interventionNames': ['Drug: Ezetimibe']}, {'type': 'PLACEBO_COMPARATOR', 'label': 'Placebo', 'interventionNames': ['Drug: Placebo']}], 'interventions': [{'name': 'Ezetimibe', 'type': 'DRUG', 'otherNames': ['Ezetrol'], 'description': 'Ezetimibe 10 mg/d for 12 weeks', 'armGroupLabels': ['Ezetimibe']}, {'name': 'Placebo', 'type': 'DRUG', 'description': 'Placebo for 12 weeks', 'armGroupLabels': ['Placebo']}]}, 'contactsLocationsModule': {'locations': [{'zip': 'G1V 0A6', 'city': 'Québec', 'state': 'Quebec', 'country': 'Canada', 'facility': 'Laval University', 'geoPoint': {'lat': 46.81228, 'lon': -71.21454}}], 'overallOfficials': [{'name': 'Patrick Couture, MD, FRCP, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'Laval University'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'Laval University', 'class': 'OTHER'}, 'responsibleParty': {'type': 'PRINCIPAL_INVESTIGATOR', 'investigatorTitle': 'MD, FRCP, PhD', 'investigatorFullName': 'Patrick Couture', 'investigatorAffiliation': 'Laval University'}}}}