This trial is active, not recruiting.

Condition fatty liver
Treatments fenofibrate, pioglitazone, placebo
Sponsor Department of Veterans Affairs
Start date October 2005
End date August 2013
Trial size 48 participants
Trial identifier NCT01289639, CDA-2-044-08S-2


The study is designed to investigate the relationship between insulin resistance and non-alcoholic fatty liver disease (NAFLD) 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.

United States No locations recruiting
Other countries No locations recruiting

Study Design

Allocation randomized
Endpoint classification efficacy study
Intervention model parallel assignment
Masking double blind (subject, caregiver, investigator)
Primary purpose basic science
(Placebo Comparator)
matching placebo 1 po qd
placebo 1 capsule po qd
micronized fenofibrate 200 mg 1 po qd
micronized fenofibrate 200 mg 1 po qd
pioglitazone 30 mg po qd
pioglitazone 30 mg po qd

Primary Outcomes

liver/spleen ratio
time frame: 6 months

Secondary Outcomes

Peripheral insulin sensitivity Hepatic insulin sensitivity Inflammatory cytokines Lipid profile Glucose tolerance Beta-cell function
time frame: 6 months
ALT levels
time frame: 6 months
hepatic insulin sensitivity index
time frame: 6 months

Eligibility Criteria

Male or female participants from 18 years up to 80 years old.

Inclusion Criteria: Control subjects: nl liver enzymes and no history of liver disease Case subjects: NAFLD on liver biopsy within the past 3 years or presumed NAFLD with otherwise unexplained elevated ALT and fatty liver by computerized tomography (CT) scan or ultrasound - Able to comply with taking 1 pill a day for 6 months and follow-up safety visits Exclusion Criteria: - Cases: cirrhosis on liver biopsy or by clinical exam or fibrosis score - Causes of liver dysfunction other than NASH - Use of medications associated with hepatic steatosis: - glucocorticoids - estrogens - tamoxifen - amiodarone - accutane - sertraline - Use of medications that cause insulin resistance: - niacin - glucocorticoids - anti-HIV drugs or atypical antipsychotics - Use of lipid-lowering medications except stable dose statin - Use of anti-NASH drugs such as ursodeoxycholic acid, betaine milk thistle - Use of coumadin - Use of nitrates - Significant alcohol consumption: Average >20 grams/day - In subjects with diabetes, a HbA1c >7.5% or use of insulin, metformin, rosiglitazone or pioglitazone - Liver transaminases: ALT >5x upper limit of normal, - Iron saturation >50% - Creatinine >1.5 mg/dl for men and >1.4 mg/dl for women - Hematocrit <33% - Pregnancy or lactation - Significant weight loss within the past 6 months or since the liver biopsy - History of significant coronary artery disease or congestive heart failure, retinopathy

Additional Information

Official title Insulin Resistance in Non-alcoholic Fatty Liver Disease (Protocol Drug Change From Project CDA-2-044-08S)
Principal investigator Kristina Marie Utzschneider, MD
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, beta-cell function and body fat distribution. Specific Aim 2: To determine in a 6 month placebo-controlled double-blinded treatment study if treatment with pioglitazone, 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.
Trial information was received from ClinicalTrials.gov and was last updated in August 2014.
Information provided to ClinicalTrials.gov by Department of Veterans Affairs.