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Completed

NCT Number: NCT00262964

Obesity and Nonalcoholic Fatty Liver Disease

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.

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Key information

Conditions

Non-Alcoholic Fatty Liver Disease Body Weight Digestive System Diseases Fatty Liver Liver Diseases Nutrition Disorders Nutritional and Metabolic Diseases Obesity Overnutrition Overweight Pathological Conditions, Signs and Symptoms Signs and Symptoms

Age range

18 year–45 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Washington University School of Medicine

St Louis, Missouri, 63110, United States

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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.

Treatment and study plan

niacin

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.

Other names: niaspan

fenofibrate

Drug

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

Other names: Tricor

Placebo

Drug

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

Primary outcomes

  1. Hepatic Insulin Sensitivity Index (HISI)

    Time frame: 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 measures are more readable. As yet there is no normal range for HISI, since is a surrogate marker for hepatic insulin sensitivity that has not yet been validated.

  2. Percent Increase in Skeletal Muscle Insulin Sensitivity During Insulin Infusion.

    Time frame: 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.

  3. Adipose Tissue Insulin Sensitivity

    Time frame: 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.

  4. Hepatic Fat Content for Fenofibrate and Niacin Groups

    Time frame: 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.

  5. Adipose Tissue Insulin Sensitivity in Fenofibrate and Niacin Groups

    Time frame: 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 euglycemic hyperinsulinemic clamp

  6. Change From Baseline in Skeletal Muscle Insulin Sensitivity

    Time frame: 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.

  7. Change From Baseline in Hepatic Insulin Sensitivity Index

    Time frame: 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 sensitivity measures are more readable. As yet there is no normal range for HISI, since is a surrogate marker for hepatic insulin sensitivity that has not yet been validated.

Secondary outcomes

  1. Very Low Density Lipoprotein - Triglyceride Production Rate

    Time frame: 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).

  2. Change From Baseline in Very Low Density Lipoprotein Apolipoprotein B Production Rate

    Time frame: 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.

  3. Change From Baseline in VLDL-Tg Clearance Rate

    Time frame: 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.

  4. Change From Baseline in VLDL-Tg Production Rate

    Time frame: 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.

  5. Change From Baseline in Very Low-density Lipoprotein Triglyceride Concentration

    Time frame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)

    Change from baseline in very low-density lipoprotein triglyceride concentration (VLDL-Tg)

Sponsors and collaborators

Lead sponsor

Washington University School of Medicine

Other

Collaborators

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

Registry information

Important dates

Study start
2004
Primary completion
2008
Study completion
2008
First posted
Dec 7, 2005
Registry last updated
Jul 11, 2018

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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