Obesity and Nonalcoholic Fatty Liver Disease

Not Applicable

Completed

• Conditions: Non-alcoholic Fatty Liver Disease
• Interventions: Drug: placebo; Drug: fenofibrate; Drug: Niacin

• Registration Number: NCT00262964
• Lead Sponsor: Washington University School of Medicine

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:
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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 func...

Basic Information
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Recruitment & Eligibility
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Study & Design
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Trial Locations

Study Timeline

• Study Start: 2004-10
• Study First Submitted: 2005-12-06
• Study First Submitted QC: 2005-12-06
• Study First Posted: 2005-12-07
• Primary Completion: 2008-12
• Study Completion: 2008-12
• Results First Submitted: 2010-03-15
• Results First Submitted QC: 2010-05-20
• Results First Posted: 2010-06-28
• Status Verified: 2018-06
• Last Update Submitted: 2018-06-13
• Last Update Posted: 2018-07-11

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 51

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.

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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.

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: FACTORIAL

Arm && Interventions

Group	Intervention	Description
NAFLD-placebo	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.
NAFLD-fenofibrate	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.
NAFLD-Niacin	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.

Primary Outcome Measures

Name	Time	Method
Change From Baseline in Skeletal Muscle Insulin Sensitivity	baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)	Changes in skeletal muscle insulin sensitivity (SMIS). SMIS was measured as the increase in skeletal muscle glucose uptake from time zero to the end of a nine hour euglycemic clamp and insulin infusion study. This increase is the percentage change from time zero to end of insulin infusion at nine hours.
Percent Increase in Skeletal Muscle Insulin Sensitivity During Insulin Infusion.	baseline cross-sectional data pre and post nine hour euglycemic clamp	A precise measure of the ability of insulin to stimulate glucose uptake by skeletal muscle. Skeletal muscle insulin sensitivity, measured as the increase from baseline in skeletal muscle glucose uptake during insulin infusion(percentage)as part of a nine hour euglycemic hyperinsulinemic clamp study.
Hepatic Fat Content for Fenofibrate and Niacin Groups	baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)	Hepatic fat content as measured by magnetic resonance spectroscopy. A PRESS sequence was used. The results from three 10 cubic centimeter voxels positioned within the liver were averaged. The measure is a ratio of triglyceride signal to total signal.
Adipose Tissue Insulin Sensitivity	baseline cross-sectional data pre and post nine hour euglycemic clamp	The ability of insulin to suppress the release of fatty acids from adipose tissue: Adipose tissue insulin sensitivity, measured as the suppression from baseline of free fatty acid release from adipose tissue (lipolysis) during insulin infusion as part of a nine hour euglycemic hyperinsulinemic clamp study.
Adipose Tissue Insulin Sensitivity in Fenofibrate and Niacin Groups	baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)	The baseline and post-treatment measures of adipose tissue insulin sensitivity (ATIS) were compared. ATIS at both timepoints is the suppression from fasting levels of free fatty acid release from adipose tissue (lipolysis) during an insulin infusion as part of a euglycemic clamp study. It is the percent decrease from time zero to the end of the nine hour eug...
Hepatic Insulin Sensitivity Index (HISI)	baseline cross-sectional data	Hepatic insulin sensitivity, assessed as a function of glucose production rate and plasma insulin concentration. The Hepatic Insulin Sensitivity Index(HISI) is the reciprocal of glucose rate of appearance \[10000/(μmol/min)\] multiplied by insulin concentration\[mU/L\]. The 10000 in the formula is a conventional adjustment so that insulin sensitivity measure...
Change From Baseline in Hepatic Insulin Sensitivity Index	baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)	Hepatic insulin sensitivity, assessed as a function of glucose production rate and plasma insulin concentration. The Hepatic Insulin Sensitivity Index (HISI) is measured as the reciprocal of glucose rate of appearance \[10000/(μmol/min)\] multiplied by insulin concentration\[mU/L\]. The 10000 in the formula is a conventional adjustment so that insulin sensit...

Secondary Outcome Measures

Name	Time	Method
Change From Baseline in VLDL-Tg Clearance Rate	baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)	Very low density lipoprotein triglyceride (VLDL-Tg) clearance rate, a measure of VLDL-triglyceride removal from plasma per minute.
Change From Baseline in Very Low-density Lipoprotein Triglyceride Concentration	baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)	Change from baseline in very low-density lipoprotein triglyceride concentration (VLDL-Tg)
Very Low Density Lipoprotein - Triglyceride Production Rate	baseline cross-sectional data	Very low density lipoprotein triglyceride (VLDL-TG) production rate, a measure of hepatic secretion of VLDL-triglyceride per liter of plasma per minute (μmol/L/min).
Change From Baseline in VLDL-Tg Production Rate	baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)	VLDL-TG production rate, a measure of hepatic secretion of VLDL-triglyceride per liter of plasma per minute.
Change From Baseline in Very Low Density Lipoprotein Apolipoprotein B Production Rate	baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)	VLDL-apolipoprotein B (apoB) concentrations were measured as part of a VLDL metabolism study utilizing stable isotope tracers. VLDL apoB production rate, a measure of hepatic secretion of VLDL-apolipoproteinB-100 per liter of plasma per minute.

Trial Locations

Locations (1)

Washington University School of Medicine; 🇺🇸 Saint Louis, Missouri, United States