Clinical trial NCT00252499
Conditions: Fatty Liver Insulin Resistance
Keywords: beta cell function fenofibrate non-alcoholic steatohepatitis rosiglitazone insulin sensitivity
Sponsor: US Department of Veterans Affairs
Start date: 2005-10-01; Completion date: 2010-08-01
Enrollment: 13 participants; Allocation: RANDOMIZED; Intervention model: PARALLEL

Brief summary:
The purpose of this study is to determine whether nonalcoholic fatty liver disease (NAFLD) is associated with altered peripheral and hepatic insulin sensitivity and to investigate potential mechanisms underlying insulin resistance in NAFLD by determining associations between hepatic and peripheral insulin sensitivity, hepatic steatosis, dyslipidemia, inflammatory cytokines, glucose metabolism, beta-cell function and body fat distribution.

Detailed description:
NAFLD and nonalcoholic steatohepatitis (NASH) are common liver disorders that are strongly associated with obesity, type 2 diabetes and dyslipidemia. The underlying pathophysiology of fatty infiltration of the liver is thought to be related to insulin resistance, which is an almost universal finding in patients with NAFLD. It is also possible that fat infiltration and inflammation in the liver may impair insulin sensitivity, either locally in the liver, or peripherally via the actions of inflammatory cytokines. We hypothesize that insulin resistance is a major causal factor leading to fat deposition in the liver and NAFLD, and thus interventions aimed at improving insulin sensitivity will result in a reduction of hepatic inflammation and steatosis.

Specific Aim 1: To determine in a cross-sectional study whether NAFLD is associated with altered peripheral and hepatic insulin sensitivity and to study their relationships with hepatic steatosis, dyslipidemia, inflammatory cytokines, glucose metabolism, -cell function and body fat distribution. Specific Aim 2: To determine in a 6 month placebo-controlled double-blinded treatment study if treatment with rosiglitazone, an insulin sensitizer, or fenofibrate, a triglyceride lowering agent, will improve both hepatic as well as peripheral insulin sensitivity and thereby improve hepatic steatosis and inflammation in subjects with NAFLD.

The results of the proposed study will have important implications for our understanding of the mechanisms underlying insulin resistance and abnormalities in lipid and glucose metabolism in subjects with NAFLD and for the design of future studies aimed at the prevention and treatment of this condition.

Arms: arm 1: matching placebo for rosiglitazone, 1 po bid and placebo for fenofibrate 1 po qd arm 2: rosiglitazone 4 mg po bid and fenofibrate placebo 1 po qd arm 3: micronized fenofibrate 200 mg 1 po qd and rosiglitazone placebo 1 po bid
Interventions: intervention 1: rosiglitazone intervention 2: fenofibrate intervention 3: placebo for rosiglitazone intervention 4: placebo for fenofibrate
Intervention descriptions: intervention 1: PPAR-gamma agonist, insulin sensitizer intervention 2: PPAR-alpha agonist, reduces triglycerides intervention 3: placebo tablets that are matched to look like rosiglitazone intervention 4: placebo matched to look like fenofibrate tablets

Protocol documents: