Clinical Trials Logo

Clinical Trial Details — Status: Terminated

Administrative data

NCT number NCT00529204
Other study ID # H80-MC-X006
Secondary ID
Status Terminated
Phase Phase 2
First received September 12, 2007
Last updated December 22, 2014
Start date October 2007
Est. completion date February 2010

Study information

Verified date December 2014
Source University of California, Davis
Contact n/a
Is FDA regulated No
Health authority United States: Institutional Review Board
Study type Interventional

Clinical Trial Summary

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.


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.


Recruitment information / eligibility

Status Terminated
Enrollment 1
Est. completion date February 2010
Est. primary completion date July 2009
Accepts healthy volunteers No
Gender Both
Age group 18 Years to 70 Years
Eligibility 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 Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment


Related Conditions & MeSH terms


Intervention

Drug:
exenatide
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

Locations

Country Name City State
United States University of California Davis Medical Center Sacramento California

Sponsors (3)

Lead Sponsor Collaborator
University of California, Davis Amylin Pharmaceuticals, LLC., Eli Lilly and Company

Country where clinical trial is conducted

United States, 

References & Publications (1)

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. — View Citation

Outcome

Type Measure Description Time frame Safety issue
Primary Reduction in Serum ALT From Baseline to 24 Weeks of Exenatide Therapy 24 weeks Yes
Secondary Changes in Components of Liver Histology at Baseline and Week 24 Including Steatosis, Inflammation and Fibrosis 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 No
Secondary Safety of Exenatide in Patients With NAFLD and Type 2 Diabetes 24 weeks Yes
See also
  Status Clinical Trial Phase
Recruiting NCT05979779 - Ph 2 Study of the Safety and Efficacy of Three HU6 Dose Levels and Placebo in Nonalcoholic Steatohepatitis Phase 2
Recruiting NCT06051669 - Comparison of iLivTouch and FibroScan for the Assessment of Liver Fibrosis and Steatosis in Adult Patients in the US
Not yet recruiting NCT05984745 - Effect of CoQ10 on the Outcome of MAFLD Patients Phase 2
Completed NCT02565446 - Transforming Non-Invasive Liver Disease Detection by MRE: The Hepatogram N/A
Not yet recruiting NCT01694342 - Telomere Parameters in Patients With Nonalcoholic Fatty Liver N/A
Completed NCT01464801 - Resveratrol in Patients With Non-alcoholic Fatty Liver Disease N/A
Completed NCT01992809 - Omega 3 Supplementation in Fatty Liver Phase 3
Completed NCT00244569 - Development of a Breath Test for Monitoring Patients With Liver Disease Phase 3
Completed NCT00063635 - Treatment of Nonalcoholic Fatty Liver Disease in Children (TONIC) Phase 3
Recruiting NCT03972319 - Omega-3 Supplementation for LIver VolumE Reduction Study (OLIVER) Study Early Phase 1
Completed NCT03141008 - Evaluation of Liver and Cardiometabolic Health Benefits on Low Carbohydrate Ketogenic Diet
Completed NCT03614039 - Effect of Probiotic and Smectite Gel on NAFLD N/A
Recruiting NCT05125757 - Lifestyle Modification in Psoriatic Patients With Fatty Liver N/A
Recruiting NCT05370053 - The Availability of the Enhanced Liver Fibrosis (ELF) Test Affects the Rate of Diagnosis of Nonalcoholic Steatohepatitis (NASH) With Fibrosis in Patients Referred to Hepatology N/A
Recruiting NCT04371042 - PROtocol of Metabolic and Cryptogenic livEr Disease regisTry for intEgration of Omic Studies
Completed NCT04004273 - Diabetes, Exercise and Liver Fat (DELIVER) N/A
Completed NCT02520609 - Dynamic Post-Prandial Metabolism in Patients With Non-Alcoholic Fatty Liver Disease
Recruiting NCT02265276 - A Prospective, Randomized Trial to Compare saroGLitazar With pioglitAZone in Nonalcoholic Fatty livEr Disease Phase 3
Completed NCT02347007 - Impact of Almond Supplementation on Body Composition in Overweight/Obese Minority Adults N/A
Completed NCT01934777 - Efficacy and Tolerance of Treatment With DHA, Choline and Vitamin E in Children With Non-alcoholic Steatohepatitis Phase 3

External Links