{"protocolSection":{"identificationModule":{"nctId":"NCT00845182","orgStudyIdInfo":{"id":"HSC2007243H"},"organization":{"fullName":"The University of Texas Health Science Center at San Antonio","class":"OTHER"},"briefTitle":"Effect of Pioglitazone and Exenatide on Body Weight and Beta Cell Function","officialTitle":"Effect of Pioglitazone With and Without Exenatide on Body Weight, Fat Topography, Beta Cell Function, and Glycemic Control in Type 2 Diabetic Patients","acronym":"PIO-EX"},"statusModule":{"statusVerifiedDate":"2017-05","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2007-06"},"primaryCompletionDateStruct":{"date":"2010-07","type":"ACTUAL"},"completionDateStruct":{"date":"2010-07","type":"ACTUAL"},"studyFirstSubmitDate":"2009-02-17","studyFirstSubmitQcDate":"2009-02-17","studyFirstPostDateStruct":{"date":"2009-02-18","type":"ESTIMATED"},"resultsFirstSubmitDate":"2013-04-04","resultsFirstSubmitQcDate":"2015-03-13","resultsFirstPostDateStruct":{"date":"2015-03-17","type":"ESTIMATED"},"lastUpdateSubmitDate":"2017-12-18","lastUpdatePostDateStruct":{"date":"2018-01-18","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"SPONSOR"},"leadSponsor":{"name":"The University of Texas Health Science Center at San Antonio","class":"OTHER"}},"oversightModule":{"oversightHasDmc":true},"descriptionModule":{"briefSummary":"Pioglitazone, a drug used in treatment of type 2 diabetes has been shown to improve insulin sensitivity in skeletal muscle, liver, and fat cells. Despite the beneficial effects of pioglitazone to improve insulin sensitivity and reduce cardiovascular disease in high risk type 2 diabetic patients, weight gain has been a limiting factor. Exenatide, another agent used for treatment of T2DM, improves glycemic control and promotes moderate weight loss. In this proposal we will examine the effect of combination therapy with pioglitazone plus exenatide on body weight, fat topography, beta cell function, glycemic control, and plasma lipid levels in subjects with type 2 diabetes mellitus compared to treatment with each drug separately. Assessment of beta cell function will be performed by measuring the maximal insulin secretory capacity using a maximal hyperglycemic stimulus combined with an intravenous arginine stimulus.","detailedDescription":"The thiazolidinedione (TZD) class of drugs has been shown to improve insulin sensitivity in skeletal muscle, liver, and adipocytes and to have anti-inflammatory and cardioprotective effects. The beta cell function, measured by the insulin secretion/insulin resistance index during the OGTT, improves significantly. In the present study, we will perform a more definitive assessment of beta cell function in TZD-treated diabetic patients by measuring the maximal insulin secretory capacity using a maximal hyperglycemic stimulus combined with an intravenous arginine stimulus.\n\nDespite the beneficial effects of pioglitazone to improve insulin sensitivity and reduce cardiovascular events in high risk type 2 diabetic patients, weight gain has been a limiting factor for primary care physicians even though pioglitazone treatment leads to a redistribution of fat out of muscle/liver/visceral area to subcutaneous fat.\n\nExenatide (Byetta) is 39 amino acid peptide which exhibits biological actions similar to GLP-1. In clinical trials exenatide reduces HbA1c by 1-1.2% in subjects with type 2 diabetes and promotes moderate weight loss which is sustained for up to 2 years.\n\nIn this proposal we will examine the effect of combination therapy with pioglitazone plus exenatide on body weight, fat topography, beta cell function, glycemic control, and plasma lipid levels in subjects with type 2 diabetes mellitus compared to monotherapy with each agent separately. We postulate that combination therapy will result in significant weight loss (in contrast to the weight gain which accompanies pioglitazone treatment) and have an additive, or even synergistic, effect to improve beta cell function and glycemic control in type 2 diabetic patients who are inadequately controlled on oral agent therapy with metformin alone, a sulfonylurea alone, or combination of metformin plus a sulfonylurea. We will also compare the insulin secretion in healthy control subjects (NGT, n=15) and subjects with impaired glucose tolerance (IGT, n=15) to evaluate the relative decline in beta cell function in T2DM compared to NGT and IGT subjects. NGT and IGT subjects will participate only in a OGTT and a Hyperglycemic clamp- they will not receive any medication."},"conditionsModule":{"conditions":["Type 2 Diabetes","Healthy","Impaired Glucose Tolerance"],"keywords":["Type 2 diabetes pathogenesis, thiazolidinediones","impaired glucose tolerance","Incretins","Insulin secretion"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE4"],"designInfo":{"allocation":"RANDOMIZED","interventionModel":"PARALLEL","primaryPurpose":"TREATMENT","maskingInfo":{"masking":"SINGLE","whoMasked":["PARTICIPANT"]}},"enrollmentInfo":{"count":43,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"Pioglitazone","type":"ACTIVE_COMPARATOR","description":"Pioglitazone: 15 Patients will be randomized to Pioglitazone only arm","interventionNames":["Drug: Pioglitazone"]},{"label":"Exenatide","type":"EXPERIMENTAL","description":"Exenatide: 15 subjects will be randomized to receive Exenatide","interventionNames":["Drug: Exenatide"]},{"label":"Drug Pioglitazone and Drug Exentatide","type":"EXPERIMENTAL","description":"Pioglitazone and Exenatide: 15 subjects will be randomized to Pioglitazone and Exenatide","interventionNames":["Drug: Pioglitazone and Exenatide"]}],"interventions":[{"type":"DRUG","name":"Pioglitazone","description":"Pioglitazone 15 mg/day for 1 month and then 45 mg/day for 5 months","armGroupLabels":["Pioglitazone"],"otherNames":["ACTOS"]},{"type":"DRUG","name":"Exenatide","description":"Exenatide 5mcg twice daily for 1 month, then 10mcg twice daily for 5 months","armGroupLabels":["Exenatide"],"otherNames":["BYETTA"]},{"type":"DRUG","name":"Pioglitazone and Exenatide","description":"Pioglitazone 30mg daily for 1 month and then 45mg daily for 5 months and Exenatide 5mcg twice daily for one month then 10mcg twice daily for 5 months","armGroupLabels":["Drug Pioglitazone and Drug Exentatide"],"otherNames":["ACTOS","BYETTA"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Effect of Pioglitazone, Exenatide and Combined Pioglitazone and Exenatide on Body Weight","description":"Effect of Pioglitazone, Exenatide and combined Pioglitazone and Exenatide on body weight and beta cell function","timeFrame":"baseline and 6 months"},{"measure":"HbA1c","description":"change in HbA1c was measured before and after treatment in three groups","timeFrame":"baseline and 6 months"}],"secondaryOutcomes":[{"measure":"Effect Pioglitazone, Exenatide, and Pioglitazone Plus Exenatide • Insulin Sensitivity • Inflammatory Cytokines • Glucagon and Free Fatty Acids • Plasma Lipids","description":"Effect pioglitazone, exenatide, and pioglitazone plus exenatide on\n\n* Insulin sensitivity\n* Inflammatory cytokines\n* glucagon and free fatty acids\n* plasma lipids measured over a 6 month period","timeFrame":"6 months"}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n1. Diabetic patients must be on diet therapy alone or diet plus a sulfonylurea, or diet plus metformin, or diet plus sulfonylurea/metformin and have a HbA1c ≥ 7.0%.\n2. Patients must have the following laboratory values:\n\n   Hematocrit ≥ 34 vol% Serum creatinine ≤ 1.8 mg/dl AST (SGOT) ≤ 2 times upper limit of normal ALT (SGPT) ≤ 2 times upper limit of normal Alkaline phosphatase ≤ 2 times upper limit of normal\n3. Patients must have been on a stable dose of allowed chronic medications for 30 days prior to entering the study.\n4. Body weight must be stable (± 3-4 pounds) over the three months prior to study\n5. The normal healthy control group will be age, weight (BMI), and gender matched with the diabetic group and must have a normal OGTT according to ADA criteria.\n6. Subjects with IFG/IGT will have a FPG (100-125mg/dl) and/or 2-h plasma glucose (140-199mg/dl) according to ADA criteria.\n\nExclusion Criteria:\n\n1. Patients must not have type 1 diabetes.\n2. Patients must not have a fasting plasma glucose of greater than 270 mg/dl or HbA1c \\> 10.0%.\n3. Patients must not have received a thiazolidinedione or insulin for more than one week during the year prior to randomization.\n4. Patients with a history of clinically significant heart disease (New York Heart Classification greater than class 2.","healthyVolunteers":true,"sex":"ALL","minimumAge":"18 Years","maximumAge":"65 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Devjit Tripathy, MD","affiliation":"The University of Texas Health Science Center at San Antonio","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"Barter Research Center, ALM VA Hospital","city":"San Antonio","state":"Texas","zip":"78229","country":"United States","geoPoint":{"lat":29.42412,"lon":-98.49363}}]},"referencesModule":{"references":[{"pmid":"27624579","type":"DERIVED","citation":"Guardado-Mendoza R, Chavez AO, Jimenez-Ceja LM, Hansis-Diarte A, DeFronzo RA, Folli F, Tripathy D. Islet amyloid polypeptide response to maximal hyperglycemia and arginine is altered in impaired glucose tolerance and type 2 diabetes mellitus. Acta Diabetol. 2017 Jan;54(1):53-61. doi: 10.1007/s00592-016-0904-7. Epub 2016 Sep 13."}]}},"resultsSection":{"participantFlowModule":{"groups":[{"id":"FG000","title":"Pioglitazone","description":"Pioglitazone: 15 Patients will be randomized to Pioglitazone only arm"},{"id":"FG001","title":"Exenatide","description":"Exenatide: 15 subjects will be randomized to receive Exenatide"},{"id":"FG002","title":"Pioglitazone and Exentatide","description":"Pioglitazone and Exenatide: 15 subjects will be randomized to Pioglitazone and Exenatide"}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"13"},{"groupId":"FG001","numSubjects":"15"},{"groupId":"FG002","numSubjects":"15"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"10"},{"groupId":"FG001","numSubjects":"11"},{"groupId":"FG002","numSubjects":"9"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"3"},{"groupId":"FG001","numSubjects":"4"},{"groupId":"FG002","numSubjects":"6"}]}],"dropWithdraws":[{"type":"Lost to Follow-up","reasons":[{"groupId":"FG000","numSubjects":"3"},{"groupId":"FG001","numSubjects":"3"},{"groupId":"FG002","numSubjects":"4"}]},{"type":"Adverse Event","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"1"},{"groupId":"FG002","numSubjects":"1"}]},{"type":"Physician Decision","reasons":[{"groupId":"FG000","numSubjects":"0"},{"groupId":"FG001","numSubjects":"0"},{"groupId":"FG002","numSubjects":"1"}]}]}]},"baselineCharacteristicsModule":{"groups":[{"id":"BG000","title":"Pioglitazone","description":"Pioglitazone: 15 Patients will be randomized to Pioglitazone only arm"},{"id":"BG001","title":"Exenatide","description":"Exenatide: 15 subjects will be randomized to receive Exenatide"},{"id":"BG002","title":"Pioglitazone and Exentatide","description":"Pioglitazone and Exenatide: 15 subjects will be randomized to Pioglitazone and Exenatide"},{"id":"BG003","title":"Total","description":"Total of all reporting groups"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"13"},{"groupId":"BG001","value":"15"},{"groupId":"BG002","value":"15"},{"groupId":"BG003","value":"43"}]}],"measures":[{"title":"Age, Categorical","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"<=18 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"0"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"0"}]},{"title":"Between 18 and 65 years","measurements":[{"groupId":"BG000","value":"13"},{"groupId":"BG001","value":"14"},{"groupId":"BG002","value":"15"},{"groupId":"BG003","value":"42"}]},{"title":">=65 years","measurements":[{"groupId":"BG000","value":"0"},{"groupId":"BG001","value":"1"},{"groupId":"BG002","value":"0"},{"groupId":"BG003","value":"1"}]}]}]},{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"STANDARD_DEVIATION","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"54.6","spread":"5.7"},{"groupId":"BG001","value":"54.3","spread":"8.5"},{"groupId":"BG002","value":"53.8","spread":"9.8"},{"groupId":"BG003","value":"54.2","spread":"8.02"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"4"},{"groupId":"BG001","value":"4"},{"groupId":"BG002","value":"5"},{"groupId":"BG003","value":"13"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"9"},{"groupId":"BG001","value":"11"},{"groupId":"BG002","value":"10"},{"groupId":"BG003","value":"30"}]}]}]},{"title":"Region of Enrollment","paramType":"NUMBER","unitOfMeasure":"participants","classes":[{"title":"United States","categories":[{"measurements":[{"groupId":"BG000","value":"13"},{"groupId":"BG001","value":"15"},{"groupId":"BG002","value":"15"},{"groupId":"BG003","value":"43"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Effect of Pioglitazone, Exenatide and Combined Pioglitazone and Exenatide on Body Weight","description":"Effect of Pioglitazone, Exenatide and combined Pioglitazone and Exenatide on body weight and beta cell function","populationDescription":"we analyzed the weight at the end of study completion","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"kg","timeFrame":"baseline and 6 months","groups":[{"id":"OG000","title":"PIOGLITAZONE","description":"PIO therapy led to a weigh gain of 5.5 kg"},{"id":"OG001","title":"EXENATIDE","description":"PIO therapy led to a weigh loss of 2.4 kg"},{"id":"OG002","title":"PIOGLITAZONE and EXNATIDE","description":"Combinatiton of PIoglitazone and Exenatide led to weight gain of 2.7 kg"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"},{"groupId":"OG001","value":"11"},{"groupId":"OG002","value":"9"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"5.5","spread":"7.3"},{"groupId":"OG001","value":"2.4","spread":"2.8"},{"groupId":"OG002","value":"2.7","spread":"4.4"}]}]}],"analyses":[{"groupIds":["OG000","OG001","OG002"],"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"<0.05","statisticalMethod":"ANCOVA","ciNumSides":"TWO_SIDED"},{"groupIds":["OG000","OG001","OG002"],"nonInferiorityType":"SUPERIORITY_OR_OTHER","pValue":"<0.05","statisticalMethod":"ANOVA","ciNumSides":"TWO_SIDED"}]},{"type":"PRIMARY","title":"HbA1c","description":"change in HbA1c was measured before and after treatment in three groups","populationDescription":"There was a greater improvement in HbA1c from baseline after combined treatment with Pioglitazone and Exenatide when compared with either therapy alone.","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"percent point decrease from baseline","timeFrame":"baseline and 6 months","groups":[{"id":"OG000","title":"Pioglitazone","description":"Pioglitazone: 15 Patients will be randomized to Pioglitazone only arm\n\nPioglitazone: Pioglitazone 15 mg/day for 1 month and then 45 mg/day for 5 months"},{"id":"OG001","title":"Exenatide","description":"Exenatide: 15 subjects will be randomized to receive Exenatide\n\nExenatide: Exenatide 5mcg twice daily for 1 month, then 10mcg twice daily for 5 months"},{"id":"OG002","title":"Drug Pioglitazone and Drug Exentatide","description":"Pioglitazone and Exenatide: 15 subjects will be randomized to Pioglitazone and Exenatide\n\nPioglitazone and Exenatide: Pioglitazone 30mg daily for 1 month and then 45mg daily for 5 months and Exenatide 5mcg twice daily for one month then 10mcg twice daily for 5 months"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"10"},{"groupId":"OG001","value":"11"},{"groupId":"OG002","value":"9"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"1.37","spread":"0.68"},{"groupId":"OG001","value":"1.09","spread":"0.68"},{"groupId":"OG002","value":"1.91","spread":"1.20"}]}]}]},{"type":"SECONDARY","title":"Effect Pioglitazone, Exenatide, and Pioglitazone Plus Exenatide • Insulin Sensitivity • Inflammatory Cytokines • Glucagon and Free Fatty Acids • Plasma Lipids","description":"Effect pioglitazone, exenatide, and pioglitazone plus exenatide on\n\n* Insulin sensitivity\n* Inflammatory cytokines\n* glucagon and free fatty acids\n* plasma lipids measured over a 6 month period","populationDescription":"Data were not collected for this analysis","reportingStatus":"POSTED","timeFrame":"6 months","groups":[{"id":"OG000","title":"Effect Pioglitazone, Exenatide, and Pioglitazone Plus Exenatid","description":"Effect pioglitazone, exenatide, and pioglitazone plus exenatide on\n\n* Insulin sensitivity\n* Inflammatory cytokines\n* glucagon and free fatty acids\n* plasma lipids measured over a 6 month period"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"0"}]}]}]},"adverseEventsModule":{"frequencyThreshold":"5","timeFrame":"Patients were followed for 6 months.","eventGroups":[{"id":"EG000","title":"Pioglitazone","description":"Pioglitazone: 15 Patients will be randomized to Pioglitazone only arm","seriousNumAffected":0,"seriousNumAtRisk":12,"otherNumAffected":2,"otherNumAtRisk":12},{"id":"EG001","title":"Exenatide","description":"Exenatide: 15 subjects will be randomized to receive Exenatide","seriousNumAffected":0,"seriousNumAtRisk":15,"otherNumAffected":1,"otherNumAtRisk":15},{"id":"EG002","title":"Pioglitazone and Exentatide","description":"Pioglitazone and Exenatide: 15 subjects will be randomized to Pioglitazone and Exenatide","seriousNumAffected":0,"seriousNumAtRisk":15,"otherNumAffected":1,"otherNumAtRisk":15}],"otherEvents":[{"term":"weight gain","organSystem":"General disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","notes":"2 patients in the Pioglitazone had weight gain \\>10kg","stats":[{"groupId":"EG000","numEvents":2,"numAffected":2,"numAtRisk":12},{"groupId":"EG001","numEvents":0,"numAffected":0,"numAtRisk":15},{"groupId":"EG002","numEvents":1,"numAffected":1,"numAtRisk":15}]},{"term":"nausea","organSystem":"General disorders","assessmentType":"SYSTEMATIC_ASSESSMENT","notes":"one patientin exenatide group had persistent nausea and dropped out","stats":[{"groupId":"EG000","numEvents":0,"numAffected":0,"numAtRisk":12},{"groupId":"EG001","numEvents":1,"numAffected":1,"numAtRisk":15},{"groupId":"EG002","numEvents":0,"numAffected":0,"numAtRisk":15}]}]},"moreInfoModule":{"certainAgreement":{"piSponsorEmployee":false,"restrictiveAgreement":false},"pointOfContact":{"title":"Devjit Tripathy","organization":"UTexas_SanAntonio","email":"tripathy@uthscsa.edu","phone":"2105676691"}}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-09"},"conditionBrowseModule":{"meshes":[{"id":"D003924","term":"Diabetes Mellitus, Type 2"},{"id":"D018149","term":"Glucose Intolerance"}],"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":"D006943","term":"Hyperglycemia"}]},"interventionBrowseModule":{"meshes":[{"id":"D000077205","term":"Pioglitazone"},{"id":"D000077270","term":"Exenatide"}],"ancestors":[{"id":"D045162","term":"Thiazolidinediones"},{"id":"D013844","term":"Thiazoles"},{"id":"D013457","term":"Sulfur Compounds"},{"id":"D009930","term":"Organic Chemicals"},{"id":"D001393","term":"Azoles"},{"id":"D006573","term":"Heterocyclic Compounds, 1-Ring"},{"id":"D006571","term":"Heterocyclic Compounds"},{"id":"D010455","term":"Peptides"},{"id":"D000602","term":"Amino Acids, Peptides, and Proteins"},{"id":"D014688","term":"Venoms"},{"id":"D045424","term":"Complex Mixtures"},{"id":"D014118","term":"Toxins, Biological"},{"id":"D001685","term":"Biological Factors"}]}},"hasResults":true}