search
Back to results

Obesity and Nonalcoholic Fatty Liver Disease

Primary Purpose

Non-alcoholic Fatty Liver Disease

Status
Completed
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Niacin
fenofibrate
placebo
Sponsored by
Washington University School of Medicine
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Non-alcoholic Fatty Liver Disease focused on measuring non-alcoholic fatty liver disease, obesity, fatty liver disease

Eligibility Criteria

18 Years - 45 Years (Adult)All SexesDoes not accept 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.

Sites / Locations

  • Washington University School of Medicine

Arms of the Study

Arm 1

Arm 2

Arm 3

Arm 4

Arm Type

Experimental

No Intervention

Experimental

Placebo Comparator

Arm Label

NAFLD-Niacin

Control

NAFLD-fenofibrate

NAFLD-placebo

Arm 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.

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.

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

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.

Outcomes

Primary Outcome Measures

Hepatic Insulin Sensitivity Index (HISI)
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.
Percent Increase in Skeletal Muscle Insulin Sensitivity During Insulin Infusion.
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.
Adipose Tissue Insulin Sensitivity
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.
Hepatic Fat Content for Fenofibrate and Niacin Groups
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 in Fenofibrate and Niacin Groups
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
Change From Baseline in Skeletal Muscle Insulin Sensitivity
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.
Change From Baseline in Hepatic Insulin Sensitivity Index
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 Outcome Measures

Very Low Density Lipoprotein - Triglyceride Production Rate
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 Very Low Density Lipoprotein Apolipoprotein B Production Rate
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.
Change From Baseline in VLDL-Tg Clearance Rate
Very low density lipoprotein triglyceride (VLDL-Tg) clearance rate, a measure of VLDL-triglyceride removal from plasma per minute.
Change From Baseline in VLDL-Tg Production Rate
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 Triglyceride Concentration
Change from baseline in very low-density lipoprotein triglyceride concentration (VLDL-Tg)

Full Information

First Posted
December 6, 2005
Last Updated
June 13, 2018
Sponsor
Washington University School of Medicine
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
search

1. Study Identification

Unique Protocol Identification Number
NCT00262964
Brief Title
Obesity and Nonalcoholic Fatty Liver Disease
Official Title
Obesity and Nonalcoholic Fatty Liver Disease
Study Type
Interventional

2. Study Status

Record Verification Date
June 2018
Overall Recruitment Status
Completed
Study Start Date
October 2004 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
December 2008 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Washington University School of Medicine
Collaborators
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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: obesity causes hepatic fat accumulation because of excessive fatty acid release from fat tissue and increased free fatty acid availability, increased hepatic (liver) fat content causes insulin-resistant glucose (sugar) production by the liver and altered liver protein synthesis, increased hepatic fat content causes increased lipid (fat) peroxidation, hepatic inflammation, necrosis and fibrosis, and 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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Non-alcoholic Fatty Liver Disease
Keywords
non-alcoholic fatty liver disease, obesity, fatty liver disease

7. Study Design

Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Factorial Assignment
Masking
Participant
Allocation
Randomized
Enrollment
51 (Actual)

8. Arms, Groups, and Interventions

Arm Title
NAFLD-Niacin
Arm Type
Experimental
Arm 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.
Arm Title
Control
Arm Type
No Intervention
Arm 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.
Arm Title
NAFLD-fenofibrate
Arm Type
Experimental
Arm 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.
Arm Title
NAFLD-placebo
Arm Type
Placebo Comparator
Arm 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.
Intervention Type
Drug
Intervention Name(s)
Niacin
Other Intervention Name(s)
niaspan
Intervention Description
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
Intervention Name(s)
fenofibrate
Other Intervention Name(s)
Tricor
Intervention Description
Subjects randomized to fenofibrate will be treated with 200 mgs per day for eight weeks.
Intervention Type
Drug
Intervention Name(s)
placebo
Intervention Description
Subjects randomized to placebo will be treated with one placebo pill per day for eight weeks.
Primary Outcome Measure Information:
Title
Hepatic Insulin Sensitivity Index (HISI)
Description
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.
Time Frame
baseline cross-sectional data
Title
Percent Increase in Skeletal Muscle Insulin Sensitivity During Insulin Infusion.
Description
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.
Time Frame
baseline cross-sectional data pre and post nine hour euglycemic clamp
Title
Adipose Tissue Insulin Sensitivity
Description
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.
Time Frame
baseline cross-sectional data pre and post nine hour euglycemic clamp
Title
Hepatic Fat Content for Fenofibrate and Niacin Groups
Description
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.
Time Frame
baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)
Title
Adipose Tissue Insulin Sensitivity in Fenofibrate and Niacin Groups
Description
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
Time Frame
baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)
Title
Change From Baseline in Skeletal Muscle Insulin Sensitivity
Description
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.
Time Frame
baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
Title
Change From Baseline in Hepatic Insulin Sensitivity Index
Description
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.
Time Frame
baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
Secondary Outcome Measure Information:
Title
Very Low Density Lipoprotein - Triglyceride Production Rate
Description
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).
Time Frame
baseline cross-sectional data
Title
Change From Baseline in Very Low Density Lipoprotein Apolipoprotein B Production Rate
Description
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.
Time Frame
baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)
Title
Change From Baseline in VLDL-Tg Clearance Rate
Description
Very low density lipoprotein triglyceride (VLDL-Tg) clearance rate, a measure of VLDL-triglyceride removal from plasma per minute.
Time Frame
baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
Title
Change From Baseline in VLDL-Tg Production Rate
Description
VLDL-TG production rate, a measure of hepatic secretion of VLDL-triglyceride per liter of plasma per minute.
Time Frame
baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
Title
Change From Baseline in Very Low-density Lipoprotein Triglyceride Concentration
Description
Change from baseline in very low-density lipoprotein triglyceride concentration (VLDL-Tg)
Time Frame
baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
45 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Samuel Klein, MD
Organizational Affiliation
Washington University School of Medicine
Official's Role
Principal Investigator
Facility Information:
Facility Name
Washington University School of Medicine
City
Saint Louis
State/Province
Missouri
ZIP/Postal Code
63110
Country
United States

12. IPD Sharing Statement

Learn more about this trial

Obesity and Nonalcoholic Fatty Liver Disease

We'll reach out to this number within 24 hrs