Obesity and Nonalcoholic Fatty Liver Disease

Condition(s) targeted: Non-Alcoholic Fatty Liver Disease

Intervention: niacin, fenofibrate, pioglitazone (Drug)

Phase: N/A

Status: Recruiting

Sponsored by: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Official(s) and/or principal investigator(s):
Samuel Klein, MD, Principal Investigator, Affiliation: Washington University School of Medicine

Overall contact:
Jennifer McCrea, MS, Phone: 314-362-2846, Email: jmccrea@wuslt.edu

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.

Official title: Obesity and Nonalcoholic Fatty Liver Disease

Study design: Treatment, Randomized, Single Blind (Subject), Active Control, Factorial Assignment, Efficacy Study

Primary outcome:

VLDL-TG kinetics

Insulin sensitivity in adipose tissue, liver and skeletal muscle

Hepatic fat content

Hepatic, subcutaneous fat, and intraabdominal fat cytokine production

Arterial, portal venous, and peripheral blood cytokines.

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.

Minimum age: 18 Years. Maximum age: 45 Years. Gender(s): Both.

Criteria:

Inclusion Criteria:

All

- 18 - 45 years old

Study 1

- Class I obesity (weighing less than 300 lbs).

- Abnormal liver biochemistries and scheduled for liver biopsy as part of clinical

evaluation.

Study 2

- Class II and III obese patients scheduled to undergo gastric bypass surgery.

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.

Jennifer McCrea, MS, Phone: 314-362-2846, Email: jmccrea@wuslt.edu

Washington University School of Medicine, St. Louis, Missouri 63110, United States; Recruiting
Jennifer McCrea, MS, Phone: 314-362-2846, Email: jmccrea@wustl.edu
Maureen J Egan-Palmer, MS, Phone: 314-362-3669, Email: eganm@wustl.edu
Samuel Klein, MD, Principal Investigator

Starting date: December 2003
Ending date: December 2008
Last updated: June 19, 2008