Role of Exenatide in NASH-a Pilot Study (NAFLD)

This study has been completed.
Sponsor:
Collaborator:
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by (Responsible Party):
Indiana University
ClinicalTrials.gov Identifier:
NCT00650546
First received: March 28, 2008
Last updated: June 7, 2016
Last verified: June 2016
  Purpose
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.

Condition Intervention Phase
Nonalcoholic Fatty Liver Disease
(NAFLD)
Drug: Exenatide
Phase 2
Phase 3

Study Type: Interventional
Study Design: Endpoint Classification: Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Official Title: Role of Exenatide in Treatment of NASH-a Pilot Study

Resource links provided by NLM:


Further study details as provided by Indiana University:

Primary Outcome Measures:
  • Number of Patients With Improvement in Liver Histology After Treatment With Exenatide [ Time Frame: between baseline and 24-28 weeks after initiating treatment ] [ Designated as safety issue: No ]
    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.

  • Change in NAS [ Time Frame: Between baseline and 28 weeks of treatment with exenatide, sub q, 5-10 mcq. ] [ Designated as safety issue: No ]
    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.


Enrollment: 8
Study Start Date: August 2006
Study Completion Date: August 2010
Primary Completion Date: August 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: A pre treatment NAS score
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
Drug: Exenatide
5 mcg twice a day titrated to 10 mcg twice a day
Other Name: Byetta

Detailed Description:
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.
  Eligibility

Ages Eligible for Study:   18 Years to 99 Years   (Adult, Senior)
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Well documented NASH based on clinical and histological criteria. Liver biopsy must have been obtained within 12-months prior to initiation of the study.
  • Subjects must have known diabetes (either diet controlled or only on Metformin or sulfonylureas such as glyburide or glipizide).
  • Subjects must be 18 year or older.

Exclusion Criteria:

  • Co-existing etiologies for chronic liver disease (hepatitis B or C, autoimmune or hemochromatosis, etc.).
  • Clinical or histological evidence of cirrhosis.
  • Alanine aminotransferase or aspartate aminotransferase > 300 IU/L.
  • Uncontrolled diabetes (hemoglobin A1C greater than or equal to 9%).
  • Insulin or TZD dependant DM.
  • Known human immunodeficiency virus infection.
  • 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.
  • Serum creatinine of greater than or equal to 2 mg/dl.
  • Active, serious medical disease (cardiac, renal, pulmonary, dermatologic, psychiatric illness) with likely life expectancy less 5 years.
  • Current or previous malignancy with expected life expectancy less than 5-years (other than basal cell cancer of the skin).
  • Use of drugs historically associated with NASH.
  • Histological evidence of malignancy, 4+ iron deposition, or any other type of liver disease.
  • Active substance abuse, such as alcohol,inhaled or injection drugs with the previous one year.
  • Known intolerance or allergy to exenatide (Byetta).
  • History of neuroglycopenia.
  • 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.
  • Women must not be nursing.
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT00650546

Locations
United States, Indiana
Indiana University
Indianapolis, Indiana, United States, 46202
United States, Missouri
Kansas City VA Medical Center
Kansas City, Missouri, United States
United States, Texas
Fort Sam Houston
San Antonio, Texas, United States
Sponsors and Collaborators
Indiana University
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Investigators
Principal Investigator: Naga Chalasani, MD Indiana University School of Medicine
  More Information

Publications:

Responsible Party: Indiana University
ClinicalTrials.gov Identifier: NCT00650546     History of Changes
Other Study ID Numbers: DK61737  U01DK061737 
Study First Received: March 28, 2008
Results First Received: August 31, 2015
Last Updated: June 7, 2016
Health Authority: United States: Federal Government
United States: Institutional Review Board

Keywords provided by Indiana University:
Non-alcoholic steatohepatitis
NASH

Additional relevant MeSH terms:
Liver Diseases
Fatty Liver
Non-alcoholic Fatty Liver Disease
Digestive System Diseases
Exenatide
Hypoglycemic Agents
Physiological Effects of Drugs
Incretins
Hormones
Hormones, Hormone Substitutes, and Hormone Antagonists

ClinicalTrials.gov processed this record on July 21, 2016