Clinical trial NCT00262964: Obesity and Nonalcoholic Fatty Liver Disease
Official title: Obesity and Nonalcoholic Fatty Liver Disease
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Non-alcoholic Fatty Liver Disease
Keywords: non-alcoholic fatty liver disease
obesity
fatty liver disease
Lead sponsor: Washington University School of Medicine
Sponsor class: OTHER
Collaborators: name: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
First posted: 2005-12-07
Enrollment: 51
Sex: ALL
Minimum age (years): 18
Maximum age (years): 45
Standard ages: ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

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.

Primary outcomes:
measure: Hepatic Insulin Sensitivity Index (HISI)
timeFrame: baseline cross-sectional data
measure: Percent Increase in Skeletal Muscle Insulin Sensitivity During Insulin Infusion.
timeFrame: baseline cross-sectional data pre and post nine hour euglycemic clamp
measure: Adipose Tissue Insulin Sensitivity
timeFrame: baseline cross-sectional data pre and post nine hour euglycemic clamp
measure: Hepatic Fat Content for Fenofibrate and Niacin Groups
timeFrame: baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)
measure: Adipose Tissue Insulin Sensitivity in Fenofibrate and Niacin Groups
timeFrame: baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)
measure: Change From Baseline in Skeletal Muscle Insulin Sensitivity
timeFrame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
measure: Change From Baseline in Hepatic Insulin Sensitivity Index
timeFrame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
Secondary outcomes:
measure: Very Low Density Lipoprotein - Triglyceride Production Rate
timeFrame: baseline cross-sectional data
measure: Change From Baseline in Very Low Density Lipoprotein Apolipoprotein B Production Rate
timeFrame: baseline to post intervention: 8 weeks (fenofibrate), 16 weeks (niacin)
measure: Change From Baseline in VLDL-Tg Clearance Rate
timeFrame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
measure: Change From Baseline in VLDL-Tg Production Rate
timeFrame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
measure: Change From Baseline in Very Low-density Lipoprotein Triglyceride Concentration
timeFrame: baseline to end of treatment: 8 weeks (fenofibrate), 16 weeks (niacin)
Other outcomes:
Locations:
city: Saint Louis
country: United States
facility: Washington University School of Medicine
state: Missouri
Study officials:
affiliation: Washington University School of Medicine
name: Samuel Klein, MD
role: PRINCIPAL_INVESTIGATOR
References: