Obesity and Nonalcoholic Fatty Liver Disease

The Washington University

Status: Completed

Conditions: Non-alcoholic Fatty Liver Disease

Treatments: Drug: placebo; Drug: Niacin; Drug: fenofibrate

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00262964

R01DK037948 (U.S. NIH Grant/Contract)

DK37948

Details and patient eligibility

About

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.

Full 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.

Enrollment: 51 patients

Sex: All

Ages: 18 to 45 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

All

• 18 - 45 years old
• Class I obesity, i.e. Body Mass Index (BMI) between 30 and 45.
• weight less than 300 lbs.

Exclusion criteria

• Active or previous infection with hepatitis B or C, as well as other liver disease.
• History of alcohol abuse
• Diabetes
• Medications that cause liver damage or steatosis.
• Women who are pregnant or lactating.

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Single Blind

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51 participants in 4 patient groups, including a placebo group

NAFLD-Niacin

Experimental group

Description:

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.

Treatment:

Drug: Niacin

Control

No Intervention group

Description:

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.

NAFLD-fenofibrate

Experimental group

Description:

Subjects diagnosed with NAFLD were randomized to fenofibrate, an oral medication, nightly for eight weeks. Subjects will be given a dose of 200mg/day.

Treatment:

Drug: fenofibrate

NAFLD-placebo

Placebo Comparator group

Description:

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.

Treatment:

Drug: placebo