Ignite Creation Date:
2025-12-24 @ 9:16 PM
Ignite Modification Date:
2025-12-30 @ 10:40 AM
Study NCT ID:
NCT00529204
Status:
TERMINATED
Last Update Posted:
2017-06-20
First Post:
2007-09-12
Is NOT Gene Therapy:
True
Has Adverse Events:
True
Brief Title:
Effects Of Exenatide On Liver Biochemistry, Liver Histology And Lipid Metabolism In Patients With Fatty Liver Disease
Sponsor:
Organization:
Raw JSON
{'hasResults': True, 'derivedSection': {'miscInfoModule': {'versionHolder': '2025-12-24'}, 'conditionBrowseModule': {'meshes': [{'id': 'D048909', 'term': 'Diabetes Complications'}, {'id': 'D005234', 'term': 'Fatty Liver'}, {'id': 'D065626', 'term': 'Non-alcoholic Fatty Liver Disease'}, {'id': 'D003920', 'term': 'Diabetes Mellitus'}], 'ancestors': [{'id': 'D004700', 'term': 'Endocrine System Diseases'}, {'id': 'D008107', 'term': 'Liver Diseases'}, {'id': 'D004066', 'term': 'Digestive System Diseases'}, {'id': 'D044882', 'term': 'Glucose Metabolism Disorders'}, {'id': 'D008659', 'term': 'Metabolic Diseases'}, {'id': 'D009750', 'term': 'Nutritional and Metabolic Diseases'}]}, 'interventionBrowseModule': {'meshes': [{'id': 'D000077270', 'term': 'Exenatide'}], 'ancestors': [{'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'}]}}, 'resultsSection': {'moreInfoModule': {'pointOfContact': {'email': 'chris.bowlus@ucdmc.ucdavis.edu', 'phone': '916-734-8986', 'title': 'Christopher L. Bowlus, MD', 'organization': 'University of California Davis Medical Center'}, 'certainAgreement': {'piSponsorEmployee': False, 'restrictiveAgreement': False}}, 'adverseEventsModule': {'eventGroups': [{'id': 'EG000', 'title': 'Exenatide', 'description': 'exenatide 5 µg BID s.c. daily for 28 days, followed by 10 µg BID s.c. daily from day 29 to week 24\n\nexenatide: Subjects meeting the inclusion criteria will be treated with exenatide 5 µg BID s.c. for 3-7 days, followed by 10 µg BID s.c. daily to week 24', 'otherNumAtRisk': 1, 'otherNumAffected': 0, 'seriousNumAtRisk': 1, 'seriousNumAffected': 0}], 'frequencyThreshold': '0'}, 'outcomeMeasuresModule': {'outcomeMeasures': [{'type': 'PRIMARY', 'title': 'Reduction in Serum ALT From Baseline to 24 Weeks of Exenatide Therapy', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Exenatide', 'description': 'exenatide 5 µg BID s.c. daily for 28 days, followed by 10 µg BID s.c. daily from day 29 to week 24\n\nexenatide: Subjects meeting the inclusion criteria will be treated with exenatide 5 µg BID s.c. for 3-7 days, followed by 10 µg BID s.c. daily to week 24'}], 'classes': [{'categories': [{'measurements': [{'value': '61', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '24 weeks', 'unitOfMeasure': 'IU', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Changes in Components of Liver Histology at Baseline and Week 24 Including Steatosis, Inflammation and Fibrosis', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Exenatide', 'description': 'exenatide 5 µg BID s.c. daily for 28 days, followed by 10 µg BID s.c. daily from day 29 to week 24\n\nexenatide: Subjects meeting the inclusion criteria will be treated with exenatide 5 µg BID s.c. for 3-7 days, followed by 10 µg BID s.c. daily to week 24'}], 'classes': [{'title': 'steatosis', 'categories': [{'measurements': [{'value': '-1', 'groupId': 'OG000'}]}]}, {'title': 'inflammation', 'categories': [{'measurements': [{'value': '-1', 'groupId': 'OG000'}]}]}, {'title': 'fibrosis', 'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '24 weeks', 'description': 'Steatosis was grades on a scale of 0 (\\< 5%); 1 (5%- 33%); 2 (\\> 33% - 66%); and 3 (\\> 66%).\n\nInflammation was graded on a scale of 0 (No foci); 1 (\\< 2 foci per 200 X field); 2 (2-4 foci per 200 X field); and 3 (\\>4 foci per 200 X field) Fibrosis was graded on a scale of 0 (None); 1 (Mild periportal or perisinusoidal); 2 (Moderate periportal or perisinusoidal); 3 (Bridging fibrosis); and 4 (cirrhosis)', 'unitOfMeasure': 'units on a scale', 'reportingStatus': 'POSTED'}, {'type': 'SECONDARY', 'title': 'Safety of Exenatide in Patients With NAFLD and Type 2 Diabetes', 'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'OG000'}]}], 'groups': [{'id': 'OG000', 'title': 'Exenatide', 'description': 'exenatide 5 µg BID s.c. daily for 28 days, followed by 10 µg BID s.c. daily from day 29 to week 24\n\nexenatide: Subjects meeting the inclusion criteria will be treated with exenatide 5 µg BID s.c. for 3-7 days, followed by 10 µg BID s.c. daily to week 24'}], 'classes': [{'categories': [{'measurements': [{'value': '0', 'groupId': 'OG000'}]}]}], 'paramType': 'NUMBER', 'timeFrame': '24 weeks', 'unitOfMeasure': 'adverse events', 'reportingStatus': 'POSTED'}]}, 'participantFlowModule': {'groups': [{'id': 'FG000', 'title': 'Exenatide', 'description': 'exenatide 5 µg BID s.c. daily for 28 days, followed by 10 µg BID s.c. daily from day 29 to week 24\n\nexenatide: Subjects meeting the inclusion criteria will be treated with exenatide 5 µg BID s.c. for 3-7 days, followed by 10 µg BID s.c. daily to week 24'}], 'periods': [{'title': 'Overall Study', 'milestones': [{'type': 'STARTED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '1'}]}, {'type': 'NOT COMPLETED', 'achievements': [{'groupId': 'FG000', 'numSubjects': '0'}]}]}]}, 'baselineCharacteristicsModule': {'denoms': [{'units': 'Participants', 'counts': [{'value': '1', 'groupId': 'BG000'}]}], 'groups': [{'id': 'BG000', 'title': 'Exenatide', 'description': 'exenatide 5 µg BID s.c. daily for 28 days, followed by 10 µg BID s.c. daily from day 29 to week 24\n\nexenatide: Subjects meeting the inclusion criteria will be treated with exenatide 5 µg BID s.c. for 3-7 days, followed by 10 µg BID s.c. daily to week 24'}], 'measures': [{'title': 'Age, Categorical', 'classes': [{'categories': [{'title': '<=18 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}, {'title': 'Between 18 and 65 years', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': '>=65 years', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Sex: Female, Male', 'classes': [{'categories': [{'title': 'Female', 'measurements': [{'value': '1', 'groupId': 'BG000'}]}, {'title': 'Male', 'measurements': [{'value': '0', 'groupId': 'BG000'}]}]}], 'paramType': 'COUNT_OF_PARTICIPANTS', 'unitOfMeasure': 'Participants'}, {'title': 'Alanine aminotransferase', 'classes': [{'categories': [{'measurements': [{'value': '84', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'IU', 'dispersionType': 'FULL_RANGE'}, {'title': 'Glucose', 'classes': [{'categories': [{'measurements': [{'value': '139', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'FULL_RANGE'}, {'title': 'Cholesterol', 'classes': [{'categories': [{'measurements': [{'value': '317', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'FULL_RANGE'}, {'title': 'HDL', 'classes': [{'categories': [{'measurements': [{'value': '31', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'FULL_RANGE'}, {'title': 'Triglyceride', 'classes': [{'categories': [{'measurements': [{'value': '482', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'mg/dL', 'dispersionType': 'FULL_RANGE'}, {'title': 'hsCRP', 'classes': [{'categories': [{'measurements': [{'value': '8.2', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'mg/L', 'dispersionType': 'FULL_RANGE'}, {'title': 'Weight', 'classes': [{'categories': [{'measurements': [{'value': '72.3', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': 'kg', 'dispersionType': 'FULL_RANGE'}, {'title': 'HbA1c', 'classes': [{'categories': [{'measurements': [{'value': '8.1', 'groupId': 'BG000'}]}]}], 'paramType': 'MEAN', 'unitOfMeasure': '%', 'dispersionType': 'FULL_RANGE'}]}}, 'protocolSection': {'designModule': {'phases': ['PHASE2'], 'studyType': 'INTERVENTIONAL', 'designInfo': {'allocation': 'NA', 'maskingInfo': {'masking': 'NONE'}, 'primaryPurpose': 'TREATMENT', 'interventionModel': 'SINGLE_GROUP'}, 'enrollmentInfo': {'type': 'ACTUAL', 'count': 1}}, 'statusModule': {'whyStopped': 'Lack of recruitment', 'overallStatus': 'TERMINATED', 'startDateStruct': {'date': '2007-10'}, 'expandedAccessInfo': {'hasExpandedAccess': False}, 'statusVerifiedDate': '2017-05', 'completionDateStruct': {'date': '2010-02', 'type': 'ACTUAL'}, 'lastUpdateSubmitDate': '2017-05-25', 'studyFirstSubmitDate': '2007-09-12', 'resultsFirstSubmitDate': '2014-12-08', 'studyFirstSubmitQcDate': '2007-09-12', 'lastUpdatePostDateStruct': {'date': '2017-06-20', 'type': 'ACTUAL'}, 'resultsFirstSubmitQcDate': '2014-12-15', 'studyFirstPostDateStruct': {'date': '2007-09-14', 'type': 'ESTIMATED'}, 'resultsFirstPostDateStruct': {'date': '2014-12-22', 'type': 'ESTIMATED'}, 'primaryCompletionDateStruct': {'date': '2009-07', 'type': 'ACTUAL'}}, 'outcomesModule': {'primaryOutcomes': [{'measure': 'Reduction in Serum ALT From Baseline to 24 Weeks of Exenatide Therapy', 'timeFrame': '24 weeks'}], 'secondaryOutcomes': [{'measure': 'Changes in Components of Liver Histology at Baseline and Week 24 Including Steatosis, Inflammation and Fibrosis', 'timeFrame': '24 weeks', 'description': 'Steatosis was grades on a scale of 0 (\\< 5%); 1 (5%- 33%); 2 (\\> 33% - 66%); and 3 (\\> 66%).\n\nInflammation was graded on a scale of 0 (No foci); 1 (\\< 2 foci per 200 X field); 2 (2-4 foci per 200 X field); and 3 (\\>4 foci per 200 X field) Fibrosis was graded on a scale of 0 (None); 1 (Mild periportal or perisinusoidal); 2 (Moderate periportal or perisinusoidal); 3 (Bridging fibrosis); and 4 (cirrhosis)'}, {'measure': 'Safety of Exenatide in Patients With NAFLD and Type 2 Diabetes', 'timeFrame': '24 weeks'}]}, 'oversightModule': {'oversightHasDmc': True}, 'conditionsModule': {'keywords': ['Fatty Liver', 'Nonalcoholic fatty liver disease', 'NAFDL', 'Diabetes', 'ALT', 'exenatide'], 'conditions': ['Diabetes Complications', 'Fatty Liver']}, 'referencesModule': {'references': [{'pmid': '17379054', 'type': 'BACKGROUND', 'citation': 'Buse JB, Klonoff DC, Nielsen LL, Guan X, Bowlus CL, Holcombe JH, Maggs DG, Wintle ME. Metabolic effects of two years of exenatide treatment on diabetes, obesity, and hepatic biomarkers in patients with type 2 diabetes: an interim analysis of data from the open-label, uncontrolled extension of three double-blind, placebo-controlled trials. Clin Ther. 2007 Jan;29(1):139-53. doi: 10.1016/j.clinthera.2007.01.015.'}], 'seeAlsoLinks': [{'url': 'http://www.liverfoundation.org', 'label': 'American Liver Foundation'}]}, 'descriptionModule': {'briefSummary': 'Non-alcoholic fatty liver disease (NAFLD) and non-alcoholic steatohepatitis (NASH) are common complications of type 2 diabetes and leading causes of liver disease in the US and Europe. The prevalence of NAFLD and NASH are expected to become a major cause of liver disease related deaths and liver transplantation. Currently, there are no specific therapies that alter the natural history of NAFLD.Preliminary evidence suggests that exenatide (Byetta®) may have several beneficial direct and indirect effects on NAFLD and liver lipid metabolism.', 'detailedDescription': 'Preliminary evidence suggests that exenatide (Byetta®) may have several beneficial direct and indirect effects on NAFLD and liver lipid metabolism. Ad hoc analysis of phase III studies has shown that exenatide treatment is associated with improvement and normalization of alanine aminotransferase (ALT), a marker of liver injury, and that this effect is most pronounced in those with the greatest weight loss. In addition, treatment of leptin deficient ob/ob mice with exenatide reduced weight, liver lipid content, serum ALT and liver lipid peroxidation. Additional evidence suggests that the effects of exenatide on the liver are not simply a result of weight loss, but rather due to direct effects on the liver. Hepatocytes express GLP-1 receptors that are responsive to both GLP-1 and exenatide. Furthermore, exenatide treatment of ob/ob mice or isolated hepatocytes reduces mRNA for stearoyl-CoA desaturase-1 (SCD-1) and SREBP-1c, which would be expected to reduce DNL.\n\nBased upon this data, we hypothesize that exenatide treatment of diabetic patients with NAFLD and NASH will reduce liver injury through multiple mechanisms including weight reduction associated with exenatide, improved lipid metabolism by decreased expression of hepatic genes involved in DNL and reduction of adipokines and cytokines associated with severe NASH. This study is aimed to address the potential safety and efficacy of exenatide in the treatment of NAFLD and test these hypotheses.\n\nThis will be an open label, single-arm, non-comparative trial of 20 patients with type 2 diabetes and NAFLD treated with exenatide for 6 months with the following specific aims to be assessed:\n\nDetermine the safety and efficacy of 24 weeks of exenatide treatment in diabetic patients with Non-Alcoholic Fatty Liver Disease (NAFLD) Efficacy will be measured by changes in serum ALT (primary endpoint) and liver histology.\n\nCharacterize the effects of exenatide on serum levels of adipokines and inflammatory cytokines including adiponectin, leptin and TNF- in NAFLD patients.\n\nCompare the hepatic expression of SCD1, SREBP-1c and PPAR- mRNA in NAFLD patients pre- and post-treatment with exenatide.\n\nEstablish the effects of exenatide on post-prandial lipid metabolism.\n\nDetermine the effects of exenatide on liver fibrosis in NAFLD.'}, 'eligibilityModule': {'sex': 'ALL', 'stdAges': ['ADULT', 'OLDER_ADULT'], 'maximumAge': '70 Years', 'minimumAge': '18 Years', 'healthyVolunteers': False, 'eligibilityCriteria': "Inclusion Criteria:\n\n* Age \\>18 years, \\< 70 years, inclusive\n* Type 2 diabetes on stable doses of sulfonylurea and/or metformin\n* Body mass index \\> 35 kg/m2\n* Presumed diagnosis of NAFLD based upon\n* an ALT \\> 1.5 times the upper limit of reference range,\n* no evidence of other causes of liver disease and\n* ultrasound findings compatible with fatty liver\n\nExclusion Criteria:\n\n* Clinical signs of cirrhosis as evidenced by any of the following\n* spider angiomata,\n* splenomegaly,\n* ascites\n* jaundice\n* encephalopathy\n* INR \\> 1.2\n* Platelet count \\< 100,000/ml\n* Serum albumin \\< 3.0 g/dL\n* Other liver disease including chronic viral hepatitis (B or C), alcohol abuse, hemochromatosis, alpha-1 antitrypsin deficiency, autoimmune hepatitis, Wilson's disease, primary sclerosing cholangitis or primary biliary cirrhosis.\n* Current use of \\> 20 g of alcohol per day or unwillingness to avoid alcohol during the course of the study\n* Treatment with a thiazolidinedione or exenatide within 6 months of enrolling in the study\n* AST or ALT \\> 10 times the upper limit of normal\n* Treatment with any investigational drug within 4 weeks of enrollment\n* Pre-menopausal, fertile women unwilling to use contraceptives during the study period.\n* Pregnancy or lactation\n* Initiation or change in dose of hypolipidemic drugs (statins, niacin, cholestyramine are allowed) within 6 months of enrollment\n* Use of anticoagulation, bleeding disorders or other contraindications to liver biopsy"}, 'identificationModule': {'nctId': 'NCT00529204', 'briefTitle': 'Effects Of Exenatide On Liver Biochemistry, Liver Histology And Lipid Metabolism In Patients With Fatty Liver Disease', 'organization': {'class': 'OTHER', 'fullName': 'University of California, Davis'}, 'officialTitle': 'Effects Of Exenatide (Byetta®) On Liver Biochemistry, Liver Histology And Lipid Metabolism In Patients With Non-Alcoholic Fatty Liver Disease', 'orgStudyIdInfo': {'id': '200715325'}, 'secondaryIdInfos': [{'id': 'H80-MC-X006', 'type': 'OTHER', 'domain': 'UC Davis'}]}, 'armsInterventionsModule': {'armGroups': [{'type': 'EXPERIMENTAL', 'label': 'Exenatide', 'description': 'exenatide 5 µg BID s.c. daily for 28 days, followed by 10 µg BID s.c. daily from day 29 to week 24', 'interventionNames': ['Drug: exenatide']}], 'interventions': [{'name': 'exenatide', 'type': 'DRUG', 'otherNames': ['BYETTA'], 'description': 'Subjects meeting the inclusion criteria will be treated with exenatide 5 µg BID s.c. for 3-7 days, followed by 10 µg BID s.c. daily to week 24', 'armGroupLabels': ['Exenatide']}]}, 'contactsLocationsModule': {'locations': [{'zip': '95817', 'city': 'Sacramento', 'state': 'California', 'country': 'United States', 'facility': 'University of California Davis Medical Center', 'geoPoint': {'lat': 38.58157, 'lon': -121.4944}}], 'overallOfficials': [{'name': 'Christopher L Bowlus, MD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of California, Davis'}, {'name': 'Lars Berglund, MD, PhD', 'role': 'PRINCIPAL_INVESTIGATOR', 'affiliation': 'University of California, Davis'}]}, 'sponsorCollaboratorsModule': {'leadSponsor': {'name': 'University of California, Davis', 'class': 'OTHER'}, 'collaborators': [{'name': 'Amylin Pharmaceuticals, LLC.', 'class': 'INDUSTRY'}, {'name': 'Eli Lilly and Company', 'class': 'INDUSTRY'}], 'responsibleParty': {'type': 'SPONSOR'}}}}