Effects Of Exenatide On Liver Biochemistry, Liver Histology And Lipid Metabolism In Patients With Fatty Liver Disease

NCT00529204 | Terminated Phase 2 Results DMC

• 2 other identifiers: 200715325H80-MC-X006
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Diabetes Complications; Fatty Liver

Keywords

Fatty Liver; Nonalcoholic fatty liver disease; NAFDL; Diabetes; ALT; exenatide

Outcome Measures

Primary Outcomes (1)

• Reduction in Serum ALT From Baseline to 24 Weeks of Exenatide Therapy

  24 weeks

Secondary Outcomes (2)

• Changes in Components of Liver Histology at Baseline and Week 24 Including Steatosis, Inflammation and Fibrosis

  24 weeks

• Safety of Exenatide in Patients With NAFLD and Type 2 Diabetes

  24 weeks

Study Arms (1)

Exenatide

EXPERIMENTAL

exenatide 5 µg BID s.c. daily for 28 days, followed by 10 µg BID s.c. daily from day 29 to week 24

Drug: exenatide

Interventions

exenatide DRUG

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

Also known as: BYETTA

Exenatide

Eligibility Criteria

• Age: 18 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• University of California, Davis: lead
• Amylin Pharmaceuticals, LLC.: collaborator
• Eli Lilly and Company: collaborator

Study Sites (1)

University of California Davis Medical Center

Sacramento, California, 95817, United States

Location

Related 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. doi: 10.1016/j.clinthera.2007.01.015.

  PMID: 17379054 BACKGROUND

Related Links

• American Liver Foundation

MeSH Terms

Conditions

Diabetes Complications; Fatty Liver; Non-alcoholic Fatty Liver Disease; Diabetes Mellitus

Interventions

Exenatide

Condition Hierarchy (Ancestors)

Endocrine System Diseases; Liver Diseases; Digestive System Diseases; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Peptides; Amino Acids, Peptides, and Proteins; Venoms; Complex Mixtures; Toxins, Biological; Biological Factors

Results Point of Contact

• Title: Christopher L. Bowlus, MD
• Organization: University of California Davis Medical Center

chris.bowlus@ucdmc.ucdavis.edu

916-734-8986

Study Officials

• Christopher L Bowlus, MD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

• Lars Berglund, MD, PhD

  University of California, Davis

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 12, 2007
• First Posted: September 14, 2007
• Study Start: October 1, 2007
• Primary Completion: July 1, 2009
• Study Completion: February 1, 2010
• Last Updated: June 20, 2017
• Results First Posted: December 22, 2014

Record last verified: 2017-05

Locations

US (1)