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

Indiana University

Status and phase

Completed

Phase 3

Phase 2

Conditions

Nonalcoholic Fatty Liver Disease

Treatments

Drug: Exenatide

Study type

Interventional

Funder types

Other

NIH

Identifiers

NCT00650546

DK61737

U01DK061737 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

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.

Full 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.

Enrollment

8 patients

Sex

All

Ages

18 to 99 years old

Volunteers

No Healthy Volunteers

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.