{"protocolSection":{"identificationModule":{"nctId":"NCT00650546","orgStudyIdInfo":{"id":"DK61737"},"secondaryIdInfos":[{"id":"U01DK061737","type":"NIH","link":"https://reporter.nih.gov/quickSearch/U01DK061737"}],"organization":{"fullName":"Indiana University","class":"OTHER"},"briefTitle":"Role of Exenatide in NASH-a Pilot Study","officialTitle":"Role of Exenatide in Treatment of NASH-a Pilot Study","acronym":"NAFLD"},"statusModule":{"statusVerifiedDate":"2017-03","overallStatus":"COMPLETED","expandedAccessInfo":{"hasExpandedAccess":false},"startDateStruct":{"date":"2006-08"},"primaryCompletionDateStruct":{"date":"2010-08","type":"ACTUAL"},"completionDateStruct":{"date":"2010-08","type":"ACTUAL"},"studyFirstSubmitDate":"2008-03-28","studyFirstSubmitQcDate":"2008-03-28","studyFirstPostDateStruct":{"date":"2008-04-01","type":"ESTIMATED"},"resultsFirstSubmitDate":"2015-08-31","resultsFirstSubmitQcDate":"2016-04-07","resultsFirstPostDateStruct":{"date":"2016-05-12","type":"ESTIMATED"},"lastUpdateSubmitDate":"2017-03-13","lastUpdatePostDateStruct":{"date":"2017-04-11","type":"ACTUAL"}},"sponsorCollaboratorsModule":{"responsibleParty":{"type":"SPONSOR"},"leadSponsor":{"name":"Indiana University","class":"OTHER"},"collaborators":[{"name":"National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)","class":"NIH"}]},"oversightModule":{"oversightHasDmc":false},"descriptionModule":{"briefSummary":"We hypothesize that exenatide (Byetta), a GLP-1 agonist administered subcutaneously for 24-28 weeks improves liver histology in diabetic patients with biopsy-proven NASH.","detailedDescription":"Eight adult patients with known type 2 DM(Diabetic) and biopsy-proven NAFLD were treated with 5-10 mcg subcutaneous exenatide for 28 weeks. Liver histology was assessed using the NAFLD Activity Score (NAS) prior to therapy and after 28 weeks of therapy. We used the following criteria to define our primary outcome: (i) no worsening of fibrosis score, (ii) improved score by at least one point in hepatocyte ballooning, (iii) either (a) improvement in NAS by 2 or more points spread across at least two of the three NAS components, or (b) post-treatment NAS equal or greater than 3."},"conditionsModule":{"conditions":["Nonalcoholic Fatty Liver Disease"],"keywords":["Non-alcoholic steatohepatitis","NASH"]},"designModule":{"studyType":"INTERVENTIONAL","phases":["PHASE2","PHASE3"],"designInfo":{"allocation":"NA","interventionModel":"SINGLE_GROUP","primaryPurpose":"OTHER","maskingInfo":{"masking":"NONE"}},"enrollmentInfo":{"count":8,"type":"ACTUAL"}},"armsInterventionsModule":{"armGroups":[{"label":"A pre treatment NAS score","type":"EXPERIMENTAL","description":"liver biopsy score pre treatment with exenatide 5 micrograms SQ (sub-cutaneous) twice a day titrated to 10 mcg SQ twice a day as tolerated","interventionNames":["Drug: Exenatide"]}],"interventions":[{"type":"DRUG","name":"Exenatide","description":"5 mcg twice a day titrated to 10 mcg twice a day","armGroupLabels":["A pre treatment NAS score"],"otherNames":["Byetta"]}]},"outcomesModule":{"primaryOutcomes":[{"measure":"Number of Patients With Improvement in Liver Histology After Treatment With Exenatide","description":"Number of patients with liver histology improved with exenatide. The improvement of liver histology was defined as (1) no worsening of the fibrosis score, (11) improved score by at least one point in hepatocyte ballooning, and (111) either (a) improvement in NAS (NAFLD Activity Score) by two points spread across as least two of the three NAS components, or by (B)post-treatment NAS\\<3.","timeFrame":"between baseline and 24-28 weeks after initiating treatment"},{"measure":"Change in NAS","description":"The NAFLD Activity Score (NAS) is an underweight sum of steatosis (score 0-3), inflammation (score 0-3), ballooning scores (0-2). The NAS can range from 0-8 with the higher score indicating more aggressive disease.","timeFrame":"Between baseline and 28 weeks of treatment with exenatide, sub q, 5-10 mcq."}]},"eligibilityModule":{"eligibilityCriteria":"Inclusion Criteria:\n\n* Well documented NASH based on clinical and histological criteria. Liver biopsy must have been obtained within 12-months prior to initiation of the study.\n* Subjects must have known diabetes (either diet controlled or only on Metformin or sulfonylureas such as glyburide or glipizide).\n* Subjects must be 18 year or older.\n\nExclusion Criteria:\n\n* Co-existing etiologies for chronic liver disease (hepatitis B or C, autoimmune or hemochromatosis, etc.).\n* Clinical or histological evidence of cirrhosis.\n* Alanine aminotransferase or aspartate aminotransferase \\> 300 IU/L.\n* Uncontrolled diabetes (hemoglobin A1C greater than or equal to 9%).\n* Insulin or TZD dependant DM.\n* Known human immunodeficiency virus infection.\n* Current or history of significant alcohol consumption within past 5 years. Significant alcohol consumption is defined as \\>20 grm/day in females and \\>30 grms/day in males or if alcohol consumption cannot satisfactorily be quantified.\n* Serum creatinine of greater than or equal to 2 mg/dl.\n* Active, serious medical disease (cardiac, renal, pulmonary, dermatologic, psychiatric illness) with likely life expectancy less 5 years.\n* Current or previous malignancy with expected life expectancy less than 5-years (other than basal cell cancer of the skin).\n* Use of drugs historically associated with NASH.\n* Histological evidence of malignancy, 4+ iron deposition, or any other type of liver disease.\n* Active substance abuse, such as alcohol,inhaled or injection drugs with the previous one year.\n* Known intolerance or allergy to exenatide (Byetta).\n* History of neuroglycopenia.\n* Women of childbearing potential must have had a negative pregnancy test prior to starting the study and should be willing to avoid pregnancy during the study period.\n* Women must not be nursing.","healthyVolunteers":false,"sex":"ALL","minimumAge":"18 Years","maximumAge":"99 Years","stdAges":["ADULT","OLDER_ADULT"]},"contactsLocationsModule":{"overallOfficials":[{"name":"Naga Chalasani, MD","affiliation":"Indiana University","role":"PRINCIPAL_INVESTIGATOR"}],"locations":[{"facility":"Indiana University","city":"Indianapolis","state":"Indiana","zip":"46202","country":"United States","geoPoint":{"lat":39.76838,"lon":-86.15804}},{"facility":"Kansas City VA Medical Center","city":"Kansas City","state":"Missouri","country":"United States","geoPoint":{"lat":39.09973,"lon":-94.57857}},{"facility":"Fort Sam Houston","city":"San Antonio","state":"Texas","country":"United States","geoPoint":{"lat":29.42412,"lon":-98.49363}}]},"referencesModule":{"references":[{"pmid":"16012941","type":"BACKGROUND","citation":"Adams LA, Lymp JF, St Sauver J, Sanderson SO, Lindor KD, Feldstein A, Angulo P. The natural history of nonalcoholic fatty liver disease: a population-based cohort study. Gastroenterology. 2005 Jul;129(1):113-21. doi: 10.1053/j.gastro.2005.04.014."},{"pmid":"15017611","type":"BACKGROUND","citation":"Younossi ZM, Gramlich T, Matteoni CA, Boparai N, McCullough AJ. Nonalcoholic fatty liver disease in patients with type 2 diabetes. Clin Gastroenterol Hepatol. 2004 Mar;2(3):262-5. doi: 10.1016/s1542-3565(04)00014-x."},{"pmid":"12843147","type":"BACKGROUND","citation":"Kolterman OG, Buse JB, Fineman MS, Gaines E, Heintz S, Bicsak TA, Taylor K, Kim D, Aisporna M, Wang Y, Baron AD. Synthetic exendin-4 (exenatide) significantly reduces postprandial and fasting plasma glucose in subjects with type 2 diabetes. J Clin Endocrinol Metab. 2003 Jul;88(7):3082-9. doi: 10.1210/jc.2002-021545."},{"pmid":"14752837","type":"BACKGROUND","citation":"Promrat K, Lutchman G, Uwaifo GI, Freedman RJ, Soza A, Heller T, Doo E, Ghany M, Premkumar A, Park Y, Liang TJ, Yanovski JA, Kleiner DE, Hoofnagle JH. A pilot study of pioglitazone treatment for nonalcoholic steatohepatitis. Hepatology. 2004 Jan;39(1):188-96. doi: 10.1002/hep.20012."},{"pmid":"15017657","type":"BACKGROUND","citation":"Shadid S, Jensen MD. Effect of pioglitazone on biochemical indices of non-alcoholic fatty liver disease in upper body obesity. Clin Gastroenterol Hepatol. 2003 Sep;1(5):384-7. doi: 10.1053/s1542-3565(03)00198-8."},{"pmid":"14512888","type":"BACKGROUND","citation":"Neuschwander-Tetri BA, Brunt EM, Wehmeier KR, Oliver D, Bacon BR. Improved nonalcoholic steatohepatitis after 48 weeks of treatment with the PPAR-gamma ligand rosiglitazone. Hepatology. 2003 Oct;38(4):1008-17. doi: 10.1053/jhep.2003.50420."},{"pmid":"1700785","type":"BACKGROUND","citation":"Eng J, Andrews PC, Kleinman WA, Singh L, Raufman JP. Purification and structure of exendin-3, a new pancreatic secretagogue isolated from Heloderma horridum venom. J Biol Chem. 1990 Nov 25;265(33):20259-62."},{"pmid":"1313797","type":"BACKGROUND","citation":"Eng J, Kleinman WA, Singh L, Singh G, Raufman JP. Isolation and characterization of exendin-4, an exendin-3 analogue, from Heloderma suspectum venom. Further evidence for an exendin receptor on dispersed acini from guinea pig pancreas. J Biol Chem. 1992 Apr 15;267(11):7402-5."},{"pmid":"9020121","type":"BACKGROUND","citation":"Chen YE, Drucker DJ. Tissue-specific expression of unique mRNAs that encode proglucagon-derived peptides or exendin 4 in the lizard. J Biol Chem. 1997 Feb 14;272(7):4108-15. doi: 10.1074/jbc.272.7.4108."},{"pmid":"10027577","type":"BACKGROUND","citation":"Greig NH, Holloway HW, De Ore KA, Jani D, Wang Y, Zhou J, Garant MJ, Egan JM. Once daily injection of exendin-4 to diabetic mice achieves long-term beneficial effects on blood glucose concentrations. Diabetologia. 1999 Jan;42(1):45-50. doi: 10.1007/s001250051111."},{"pmid":"21131943","type":"RESULT","citation":"Kenny PR, Brady DE, Torres DM, Ragozzino L, Chalasani N, Harrison SA. Exenatide in the treatment of diabetic patients with non-alcoholic steatohepatitis: a case series. Am J Gastroenterol. 2010 Dec;105(12):2707-9. doi: 10.1038/ajg.2010.363. No abstract available."}]}},"resultsSection":{"participantFlowModule":{"preAssignmentDetails":"This was a single arm, open label study. Only study group received exenatide treatment. Eight adult patients with known type 2 DM and biopsy-proven NAFLD were treated with 5-10mcg subcutaneous exenatide for 28 week.All eight patients were started on exenatide 5 mcg injections twice a day and the dose was increased to 10 mcg injections twice a day","recruitmentDetails":"2 recruitment sites: Department of Gastroenterology, San Antonio Uniformed Services Health Consortium, San Antonio, Texas, USA. Indiana University School of Medicine, Indianapolis, IN, USA","groups":[{"id":"FG000","title":"Exenatide Group","description":"Exenatide 5 micrograms SQ twice a day titrated to 10 mcg SQ twice a day as tolerated\n\nExenatide : 5 mcg twice a day titrated to 10 mcg twice a day"}],"periods":[{"title":"Overall Study","milestones":[{"type":"STARTED","achievements":[{"groupId":"FG000","numSubjects":"8"}]},{"type":"COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"8"}]},{"type":"NOT COMPLETED","achievements":[{"groupId":"FG000","numSubjects":"0"}]}]}]},"baselineCharacteristicsModule":{"populationDescription":"eight adult patients with known type 2 DM and biopsy -proven NAFLD were treated with 5-10 subcutaneous exenatide for 28 weeks","groups":[{"id":"BG000","title":"Open-labeled Prospective Case Series","description":"Exenatide 5 micrograms SQ twice a day titrated to 10 mcg SQ twice a day as tolerated\n\nExenatide: 5 mcg twice a day titrated to 10 mcg twice a day"}],"denoms":[{"units":"Participants","counts":[{"groupId":"BG000","value":"8"}]}],"measures":[{"title":"Age, Categorical","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"<=18 years","measurements":[{"groupId":"BG000","value":"0"}]},{"title":"Between 18 and 65 years","measurements":[{"groupId":"BG000","value":"8"}]},{"title":">=65 years","measurements":[{"groupId":"BG000","value":"0"}]}]}]},{"title":"Age, Continuous","paramType":"MEAN","dispersionType":"INTER_QUARTILE_RANGE","unitOfMeasure":"years","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"54","lowerLimit":"36","upperLimit":"65"}]}]}]},{"title":"Sex: Female, Male","paramType":"COUNT_OF_PARTICIPANTS","unitOfMeasure":"Participants","classes":[{"categories":[{"title":"Female","measurements":[{"groupId":"BG000","value":"4"}]},{"title":"Male","measurements":[{"groupId":"BG000","value":"4"}]}]}]},{"title":"Number of participants who had NAFLD Activity Score (NAS) pre/post 24-28 wks. after treatment","description":"The NAFLD Activity Score (NAS) is an underweight sum of steatosis (score 0-3), inflammation (score 0-3), ballooning scores (0-2). The NAS can range from 0-8 with the higher score indicating more aggressive disease.","paramType":"NUMBER","unitOfMeasure":"participants","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"8"}]}]}]},{"title":"NAS score","description":"steatosis, inflammation, ballooning. Each catagory has a 1 to 3 value given and the total of all 3 catagories equals the NAS overall score. 1\\] The NAFLD Activity Score (NAS) is an underweight sum of steatosis (score 0-3), inflammation (score 0-3), ballooning scores (0-2). The NAS can range from 0-8 with the higher score indicating more aggressive disease","paramType":"MEDIAN","dispersionType":"FULL_RANGE","unitOfMeasure":"units on a scale","classes":[{"categories":[{"measurements":[{"groupId":"BG000","value":"4","lowerLimit":"3","upperLimit":"5"}]}]}]}]},"outcomeMeasuresModule":{"outcomeMeasures":[{"type":"PRIMARY","title":"Number of Patients With Improvement in Liver Histology After Treatment With Exenatide","description":"Number of patients with liver histology improved with exenatide. The improvement of liver histology was defined as (1) no worsening of the fibrosis score, (11) improved score by at least one point in hepatocyte ballooning, and (111) either (a) improvement in NAS (NAFLD Activity Score) by two points spread across as least two of the three NAS components, or by (B)post-treatment NAS\\<3.","reportingStatus":"POSTED","paramType":"NUMBER","unitOfMeasure":"participants","timeFrame":"between baseline and 24-28 weeks after initiating treatment","groups":[{"id":"OG000","title":"Treatment With Exenatide","description":"eight adult patients with known type 2 DM and biopsy proven NAFLD"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"8"}]}]}]},{"type":"PRIMARY","title":"Change in NAS","description":"The NAFLD Activity Score (NAS) is an underweight sum of steatosis (score 0-3), inflammation (score 0-3), ballooning scores (0-2). The NAS can range from 0-8 with the higher score indicating more aggressive disease.","reportingStatus":"POSTED","paramType":"MEAN","dispersionType":"Standard Deviation","unitOfMeasure":"units on a scale","timeFrame":"Between baseline and 28 weeks of treatment with exenatide, sub q, 5-10 mcq.","groups":[{"id":"OG000","title":"Individuals Who Recieved Treatment With Exenatide","description":"change of NAS score in eight adult patients with known type 2 DM and biopsy proven NAFLD after treatment with exenatide"}],"denoms":[{"units":"Participants","counts":[{"groupId":"OG000","value":"8"}]}],"classes":[{"categories":[{"measurements":[{"groupId":"OG000","value":"-1.5","spread":"1.66"}]}]}]}]},"adverseEventsModule":{"frequencyThreshold":"0","timeFrame":"28 weeks","eventGroups":[{"id":"EG000","title":"Exenatide Group","description":"Exenatide 5 micrograms SQ twice a day titrated to 10 mcg SQ twice a day as tolerated\n\nExenatide : 5 mcg twice a day titrated to 10 mcg twice a day","seriousNumAffected":0,"seriousNumAtRisk":8,"otherNumAffected":2,"otherNumAtRisk":8}],"otherEvents":[{"term":"abdominal pain along with nausea","organSystem":"Gastrointestinal disorders","sourceVocabulary":"CTCAE","assessmentType":"SYSTEMATIC_ASSESSMENT","stats":[{"groupId":"EG000","numEvents":2,"numAffected":2,"numAtRisk":8}]}]},"moreInfoModule":{"limitationsAndCaveats":{"description":"As a case series our findings are limited by a control group and a small number of subjects enrolled. These limitations are tempered by the single expert hepatologist and the stringent definitions for histological improvement, ((primary end point).."},"certainAgreement":{"piSponsorEmployee":false,"restrictiveAgreement":false},"pointOfContact":{"title":"Patrick R Kenney, DO","organization":"Department of Gastroenterology, San Antonio Uniformed Services Health Consortium","email":"pat.kenney@us.army.mil"}}},"derivedSection":{"miscInfoModule":{"versionHolder":"2026-10-09"},"conditionBrowseModule":{"meshes":[{"id":"D065626","term":"Non-alcoholic Fatty Liver Disease"}],"ancestors":[{"id":"D005234","term":"Fatty Liver"},{"id":"D008107","term":"Liver Diseases"},{"id":"D004066","term":"Digestive System 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"}]}},"hasResults":true}