- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00529204
Effects Of Exenatide On Liver Biochemistry, Liver Histology And Lipid Metabolism In Patients With Fatty Liver Disease
Effects Of Exenatide (Byetta®) On Liver Biochemistry, Liver Histology And Lipid Metabolism In Patients With Non-Alcoholic Fatty Liver Disease
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Based 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.
This 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:
Determine 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.
Characterize the effects of exenatide on serum levels of adipokines and inflammatory cytokines including adiponectin, leptin and TNF- in NAFLD patients.
Compare the hepatic expression of SCD1, SREBP-1c and PPAR- mRNA in NAFLD patients pre- and post-treatment with exenatide.
Establish the effects of exenatide on post-prandial lipid metabolism.
Determine the effects of exenatide on liver fibrosis in NAFLD.
Study Type
Enrollment (Actual)
Phase
- Phase 2
Contacts and Locations
Study Locations
-
-
California
-
Sacramento, California, United States, 95817
- University of California Davis Medical Center
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age >18 years, < 70 years, inclusive
- Type 2 diabetes on stable doses of sulfonylurea and/or metformin
- Body mass index > 35 kg/m2
- Presumed diagnosis of NAFLD based upon
- an ALT > 1.5 times the upper limit of reference range,
- no evidence of other causes of liver disease and
- ultrasound findings compatible with fatty liver
Exclusion Criteria:
- Clinical signs of cirrhosis as evidenced by any of the following
- spider angiomata,
- splenomegaly,
- ascites
- jaundice
- encephalopathy
- INR > 1.2
- Platelet count < 100,000/ml
- Serum albumin < 3.0 g/dL
- 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.
- Current use of > 20 g of alcohol per day or unwillingness to avoid alcohol during the course of the study
- Treatment with a thiazolidinedione or exenatide within 6 months of enrolling in the study
- AST or ALT > 10 times the upper limit of normal
- Treatment with any investigational drug within 4 weeks of enrollment
- Pre-menopausal, fertile women unwilling to use contraceptives during the study period.
- Pregnancy or lactation
- Initiation or change in dose of hypolipidemic drugs (statins, niacin, cholestyramine are allowed) within 6 months of enrollment
- Use of anticoagulation, bleeding disorders or other contraindications to liver biopsy
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Exenatide
exenatide 5 µg BID s.c.
daily for 28 days, followed by 10 µg BID s.c.
daily from day 29 to week 24
|
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
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Reduction in Serum ALT From Baseline to 24 Weeks of Exenatide Therapy
Time Frame: 24 weeks
|
24 weeks
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Changes in Components of Liver Histology at Baseline and Week 24 Including Steatosis, Inflammation and Fibrosis
Time Frame: 24 weeks
|
Steatosis was grades on a scale of 0 (< 5%); 1 (5%- 33%); 2 (> 33% - 66%); and 3 (> 66%). Inflammation 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) |
24 weeks
|
Safety of Exenatide in Patients With NAFLD and Type 2 Diabetes
Time Frame: 24 weeks
|
24 weeks
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Lars Berglund, MD, PhD, University of California, Davis
Publications and helpful links
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 200715325
- H80-MC-X006 (Other Identifier: UC Davis)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Diabetes Complications
-
Hennepin Healthcare Research InstituteCompletedHyperglycemia | Diabetes Mellitus, Type 2 | Diabetes Mellitus | Complications of Diabetes Mellitus | Diabetes-Related ComplicationsUnited States
-
Royal Prince Alfred Hospital, Sydney, AustraliaMerck Sharp & Dohme LLCCompletedDiabetes Related Complications
-
University of Trás-os-Montes and Alto DouroCompletedType 2 Diabetes Mellitus | Diabetes-Related ComplicationsPortugal
-
Seoul St. Mary's HospitalUnknownComplications of Diabetes MellitusKorea, Republic of
-
University of AvignonCompletedDiabetes-related ComplicationsFrance
-
Albert Einstein College of MedicineJuvenile Diabetes Research Foundation; National Institutes of Health (NIH)Completed
-
Naestved HospitalUnknown
-
University of Campinas, BrazilConselho Nacional de Desenvolvimento Científico e Tecnológico; ANS PharmaUnknownDiabetes Mellitus, Type 2 | Insulin Resistance | Diabetes-Related ComplicationsBrazil
-
University of AarhusUnknownDiabetes Mellitus, Type 2 | Diabetic Neuropathies | Autonomic Neuropathy | Diabetic Complications Neurological | Polyneuropathy DiabetesDenmark
-
Singapore General HospitalSingapore Eye Research InstituteRecruitingType 2 Diabetes | Diabetes; Neuropathy, Polyneuropathy (Manifestation) | Diabetes Related Complications | Diabetes; Nephropathy (Manifestation) | Diabetes; Retinopathy (Manifestation)Singapore
Clinical Trials on exenatide
-
AstraZenecaEli Lilly and CompanyCompletedType 2 Diabetes MellitusUnited States
-
AstraZenecaCompletedType 2 Diabetes MellitusCanada, United States
-
AstraZenecaEli Lilly and CompanyCompletedType 2 Diabetes MellitusKorea, Republic of, China, Japan, Taiwan, India
-
AstraZenecaCompletedDiabetes Mellitus, Type 2United States
-
Beijing Chao Yang HospitalCompleted
-
AstraZenecaEli Lilly and CompanyCompletedType 2 Diabetes MellitusKorea, Republic of, Mexico, Germany, Greece, Argentina, India, Australia
-
AstraZenecaCelerionCompleted
-
AstraZenecaEli Lilly and CompanyCompletedType 2 Diabetes MellitusUnited States
-
AstraZenecaEli Lilly and CompanyCompletedType 2 DiabetesUnited States
-
University at BuffaloAmylin Pharmaceuticals, LLC.Completed