Clinical trial NCT00262964
Conditions: Non-alcoholic Fatty Liver Disease
Keywords: non-alcoholic fatty liver disease obesity fatty liver disease
Sponsor: Washington University School of Medicine
Start date: 2004-10-01; Completion date: 2008-12-01
Enrollment: 51 participants; Allocation: RANDOMIZED; Intervention model: FACTORIAL

Brief summary:
The primary goal of this study is to provide a better understanding of: 1) the pathogenesis and pathophysiology of non-alcoholic fatty liver disease (NAFLD) in obese subjects, and 2) the effect of marked weight loss on the histologic and metabolic abnormalities associated with NAFLD. The following hypotheses will be tested:

1. obesity causes hepatic fat accumulation because of excessive fatty acid release from fat tissue and increased free fatty acid availability,
2. increased hepatic (liver) fat content causes insulin-resistant glucose (sugar) production by the liver and altered liver protein synthesis,
3. increased hepatic fat content causes increased lipid (fat) peroxidation, hepatic inflammation, necrosis and fibrosis, and
4. marked weight loss improves NAFLD once patients are weight stable.

Detailed description:
Obesity is a major risk factor for non-alcoholic fatty liver disease (NAFLD), which represents a spectrum of liver diseases. NAFLD is a major health problem in the US because of its high prevalence and causal relationship with serious liver abnormalities. However, the mechanism(s)responsible for developing NAFLD in obese persons and the effects on liver function are not known. This gap in knowledge has made it difficult to identify effective therapy. The results from these studies will lay the groundwork for the development of novel therapeutic interventions for NAFLD in obese patients.

Arms: arm 1: Subjects, having previously diagnosed with NAFLD, were given Niacin for 16 weeks. The dosage was 500mg/day for week 1, 1000mg/day for week 2, 1500mg/day for week three and 2000mg/day for weeks 4 through 16. arm 2: Subjects were found to have intrahepatic triglyceride levels below the threshold for Non-Alcoholic Fatty Liver Disease (NAFLD). For this study that threshold was set at 10% intrahepatic triglyceride content as determined by magnetic resonance spectroscopy. These control subjects did not participate in any intervention. Only baseline features were characterized for this arm. arm 3: Subjects diagnosed with NAFLD were randomized to fenofibrate, an oral medication, nightly for eight weeks. Subjects will be given a dose of 200mg/day. arm 4: These subjects were diagnosed with Non-Alcoholic Fatty Liver Disease (NAFLD) and received an 8 week course of a placebo pill. Their baseline characteristics were averaged into the overall NAFLD baseline characteristics along with the baseline data for the two intervention groups.
Interventions: intervention 1: Niacin intervention 2: fenofibrate intervention 3: placebo
Intervention descriptions: intervention 1: Subjects randomized to Niacin therapy will be treated with Niacin at night for 16 wks to reduce plasma free fatty acid concentrations. The dose of medication will be gradually increased: 500 mg/day during week 1, 1000 mg/day during week 2, 1500 mg/day during week 3, and 2000mg/day during weeks 4-16. intervention 2: Subjects randomized to fenofibrate will be treated with 200 mgs per day for eight weeks. intervention 3: Subjects randomized to placebo will be treated with one placebo pill per day for eight weeks.

Protocol documents: