Pilot Study of Ursodesoxycholic Acid in Non-Alcoholic Steatohepatitis

Condition(s) targeted: Serum Levels of ALAT Transaminases; Serum Markers for Fibrosis and Hepatic Inflammation

Intervention: Ursodesoxycholic acid (Drug)

Phase: Phase 2

Status: Recruiting

Sponsored by: Axcan Pharma

Official(s) and/or principal investigator(s):
Vlad Ratziu, M.D., Ph.D., Principal Investigator, Affiliation: La Pitié Salpétrière Hospital, Paris, France

Overall contact:
Vlad Ratziu, M.D., Ph.D., Phone: +33 1 42 16 10 20, Email: vratziu@teaser.fr

This is a phase II study with direct individual benefit. It is a randomized, double blind placebo controlled study whose aim is to evaluate the efficacy and tolerance of ursodesoxycholic acid in patients who have been diagnosed with non-alcoholic steatohepatitis.

The hepatoprotective effects of ursodesoxycholic acid may ameliorate the hepatic impairment associated with non-alcoholic steatohepatitis leading to subsequent significant decreases in transaminase elevations and non-invasive markers for hepatic fibrosis A positive response is defined as a significantly larger decrease in average ALAT levels between the time of inclusion in the study and the end of the treatment for the ursodesoxycholic acid group as compared to the placebo group.

The duration of the study will be 12 months. An end of treatment evaluation (EoT) will take place at the end of the 12th month of treatment.

Official title: Efficacy and Safety of Ursodesoxycholic Acid in the Management of Non-Alcoholic Steatohepatitis

Study design: Treatment, Randomized, Double-Blind, Placebo Control, Parallel Assignment, Efficacy Study

Primary outcome: A positive response is defined as a significantly larger decrease in average ALAT levels between the time of inclusion in the study and the end of the treatment for the ursodesoxycholic acid group as compared to the placebo group.

Minimum age: 18 Years. Maximum age: N/A. Gender(s): Both.

Criteria:

Inclusion Criteria:

- Greater than 18 years of age.

- Hepatic biopsy consistent with non-alcoholic steatohepatitis: presence of >20%

steatosis associated with hepatocyte swelling and/or intralobular necrosis within the last 18 months.

- Serum levels of ALAT and/or ASAT > 50 UI/L at the time of screening (with at least 3

elevated transaminase values within the last 12 months).

Exclusion Criteria:

- Hepatic biopsy not performed within the last 18 months.

- A single normal transaminase value within the last 12 months.

- Treatment with ursodesoxycholic acid within the last 12 months.

- Loss of more than 15% body weight between the time of the liver biopsy and the time of

screening.

- Alcohol consumption of >20 g/day for women and > 30 g/day for men

- Hepatitis from other causes: chronic viral hepatitis B or C, elevated ferritin levels

associated with C282Y homozygosity, primary biliary cirrhosis, primary sclerosing cholangitis, well documented auto-immune hepatitis (specific autoantibodies, hypergammaglobulinemia, consistent histologic changes), alpha1 antitrypsin deficiency, Wilson’s disease, HIV infection.

- NASH from secondary causes: long term amiodarone administration, corticosteroid

therapy, anti-obesity surgery within the last 2 years, tamoxifen.

- Child’s type B or C cirrhosis.

- Presence of hepatocellular carcinoma.

- Treatment with rosiglitazone or pioglitazone currently or during the 3 preceding

years, treatment with Vitamin E within the 6 months prior to screening.

- Women who are pregnant or nursing.

- Unavailability of hepatic biopsy slides for centralized interpretation.

Vlad Ratziu, M.D., Ph.D., Phone: +33 1 42 16 10 20, Email: vratziu@teaser.fr

La Pitié Salpétrière Hospital, Paris 75013, France; Recruiting
Vlad Ratziu, M.D., Ph. D., Phone: +33 1 42 16 10 20, Email: vratziu@teaser.fr
Vlad Ratziu, M.D., Ph. D., Principal Investigator

Starting date: October 2005
Last updated: May 4, 2007