Clinical trial NCT00680407
Conditions: Non-alcoholic Steatohepatitis
Keywords: NASH non-alcoholic steatohepatitis
Sponsor: Madaus Inc
Start date: 2008-04-01; Completion date: 2012-11-01
Enrollment: 78 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
Silymarin, also known as milk thistle, is an alternative medicine commonly found in health food and vitamin stores. People with liver disease sometimes use silymarin because it is thought to have liver protecting effects; however, this benefit has not been proven. The purpose of this research study is to determine the effectiveness of silymarin and assess the safety of different silymarin doses in patients with varying severity of liver disease compared to a placebo (lactose pill).

Following a screening visit, patients with histologically confirmed NASH will be randomized to either placebo or one of two active treatment groups of silymarin (Legalon®). One active treatment group will receive 420 mg, each dose given three times daily, the other active treatment group will receive 700 mg, each dose given three times daily. Patients will be treated for 48-50 weeks. Participation in this research study requires the patient to travel to the clinic for at least 11 visits so recruitment will be limited to a geographically restricted area around participating clinical centers. Liver biopsy must be performed up to 12 months prior to, and immediately after, the treatment phase.

Detailed description:
This is a multicenter, randomized, double masked, placebo controlled Phase II trial to evaluate the safety and explore the efficacy of silymarin (Legalon®) compared with placebo on hepatic histology in patients with NASH (nonalcoholic steatohepatitis) after 48-50 weeks of therapy. This study was originally sponsored through a cooperative agreement (U01) award from the NCCAM and the NIDDK (RFA-AT-05-006: "Phase I/II Trials of Silymarin for Chronic Liver Diseases"), and now will continue with Madaus Inc. (Rottapharm Group) providing financial and regulatory support to the investigators. The broad aim of this study is to evaluate the safety and explore the efficacy of silymarin (Legalon®) in NASH patients and to form the basis for future studies which will establish its efficacy for treating patients with NASH. The specific objectives of this study are to determine the effect of silymarin (Legalon®) on the histologic NASH Activity Score (NAS), the liver enzymes, and HOMAr. The primary endpoint of the study is an improvement in the NAS by at least 2 points. Various secondary endpoints will be assessed, including the change in liver enzymes and HOMAr.

Arms: arm 1: 420 mg Legalon (silymarin) three times daily arm 2: 700 mg of Legalon (silymarin) three times daily arm 3: Placebo (lactose pill)
Interventions: intervention 1: Placebo intervention 2: Silymarin 700 mg intervention 3: Silymarin 420 mg
Intervention descriptions: intervention 1: Placebo (5 pills, three times daily) for 48-50 week treatment period intervention 2: 700 mg dose (5 pills, three times daily) for 48-50 week treatment period intervention 3: 420 mg dose (5 pills, three times daily) for 48-50 week treatment period

Protocol documents: