Clinical trial NCT00650546: Role of Exenatide in NASH-a Pilot Study
Official title: Role of Exenatide in Treatment of NASH-a Pilot Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
PHASE3
Conditions: Nonalcoholic Fatty Liver Disease
Keywords: Non-alcoholic steatohepatitis
NASH
Lead sponsor: Indiana University
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2008-04-01
Enrollment: 8
Sex: ALL
Minimum age (years): 18
Maximum age (years): 99
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief summary: 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.

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 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.

Primary outcomes:
measure: Number of Patients With Improvement in Liver Histology After Treatment With Exenatide
timeFrame: between baseline and 24-28 weeks after initiating treatment
measure: Change in NAS
timeFrame: Between baseline and 28 weeks of treatment with exenatide, sub q, 5-10 mcq.
Secondary outcomes:
Other outcomes:
Locations:
city: Indianapolis
country: United States
facility: Indiana University
state: Indiana
city: Kansas City
country: United States
facility: Kansas City VA Medical Center
state: Missouri
city: San Antonio
country: United States
facility: Fort Sam Houston
state: Texas
Study officials:
affiliation: Indiana University School of Medicine
name: Naga Chalasani, MD
role: PRINCIPAL_INVESTIGATOR
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citation: Kenny PR, Brady DE, Torres DM, Ragozzino L, Chalasani N, Harrison SA. Exenatide in the treatment of diabetic patients with non-alcoholic steatohepatitis: a case series. Am J Gastroenterol. 2010 Dec;105(12):2707-9. doi: 10.1038/ajg.2010.363. No abstract available.