Obesity and Nonalcoholic Fatty Liver Disease

NCT ID: NCT00262964

Last Updated: 2018-07-11

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 51 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2004-10-31
• Study Completion Date: 2008-12-31

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.

Conditions

Non-alcoholic Fatty Liver Disease

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: FACTORIAL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: SINGLE

Study Groups

NAFLD-Niacin

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.

Group Type: EXPERIMENTAL

Niacin

Intervention Type: DRUG

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.

Control

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.

Group Type: NO_INTERVENTION

No interventions assigned to this group

NAFLD-fenofibrate

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

Group Type: EXPERIMENTAL

fenofibrate

Intervention Type: DRUG

Subjects randomized to fenofibrate will be treated with 200 mgs per day for eight weeks.

NAFLD-placebo

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.

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

Subjects randomized to placebo will be treated with one placebo pill per day for eight weeks.

Interventions

Niacin

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 Type: DRUG

fenofibrate

Subjects randomized to fenofibrate will be treated with 200 mgs per day for eight weeks.

Intervention Type: DRUG

placebo

Subjects randomized to placebo will be treated with one placebo pill per day for eight weeks.

Intervention Type: DRUG

Other Intervention Names

niaspan; Tricor

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 45 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

NIH

Sponsor Role: collaborator

Washington University School of Medicine

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Samuel Klein, MD

Role: PRINCIPAL_INVESTIGATOR

Washington University School of Medicine

Locations

Washington University School of Medicine

St Louis, Missouri, United States

Countries

United States

Other Identifiers

R01DK037948

Identifier Type: NIH

Identifier Source: secondary_id

View Link

DK37948

Identifier Type: -

Identifier Source: org_study_id