Obesity and Nonalcoholic Fatty Liver Disease - Full Text View

Sponsored by:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Information provided by:	National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
ClinicalTrials.gov Identifier:	NCT00262964

Purpose

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.

Condition	Intervention
Non-Alcoholic Fatty Liver Disease	Drug: niacin, fenofibrate, pioglitazone

MedlinePlus related topics: Liver Diseases Obesity

Drug Information available for: Pioglitazone Pioglitazone hydrochloride Procetofen Niacin Niacin hydrochloride

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Single Blind (Subject), Active Control, Factorial Assignment, Efficacy Study
Official Title:	Obesity and Nonalcoholic Fatty Liver Disease

Further study details as provided by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK):

Primary Outcome Measures:

VLDL-TG kinetics [ Time Frame: 8-16 weeks ] [ Designated as safety issue: No ]
Insulin sensitivity in adipose tissue, liver and skeletal muscle [ Time Frame: 8-16 weeks ] [ Designated as safety issue: No ]
Hepatic fat content [ Time Frame: 8-16 weeks ] [ Designated as safety issue: No ]
Hepatic, subcutaneous fat, and intraabdominal fat cytokine production [ Time Frame: 8-16 weeks ] [ Designated as safety issue: No ]
Arterial, portal venous, and peripheral blood cytokines. [ Time Frame: 8-16 weeks ] [ Designated as safety issue: No ]

Estimated Enrollment:	40
Study Start Date:	December 2003
Estimated Study Completion Date:	December 2008
Estimated Primary Completion Date:	December 2008 (Final data collection date for primary outcome measure)

Intervention Details:

Subjects randomized to niaspan therapy will be treated with niaspan at night for 16 wks to reduce plasma FFA concentrations. The dose of medication will be gradually increased: 500 mg/day during wk 1, 1000 mg/day during wk 2, 1500 mg/day during wks 3, and 2000mg/day during wks 4-16. Subjects randomized to fenofibrate will be treated with 200 mgs per day. Subjects randomized to pioglitazone will be treated with 30 mgs per day.

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

Ages Eligible for Study:	18 Years to 45 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00262964

Contacts

Contact: Jennifer McCrea, MS	314-362-2846	jmccrea@wuslt.edu
Contact: Maureen J Egan-Palmer, MS	314-362-3669	eganm@wustl.edu

Locations

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

Sponsors and Collaborators

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

Investigators

Principal Investigator:

Samuel Klein, MD

Washington University School of Medicine

More Information

Responsible Party:	Washington University ( Samuel Klein, MD, William H. Danforth Professor of Medicine and Nutritional Science )
Study ID Numbers:	DK37948
Study First Received:	December 6, 2005
Last Updated:	June 19, 2008
ClinicalTrials.gov Identifier:	NCT00262964
Health Authority:	United States: Federal Government

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

non-alcoholic fatty liver disease
obesity
fatty liver disease

Study placed in the following topic categories:

Obesity
Liver Diseases
Non-alcoholic steatohepatitis (NASH)
Pioglitazone
Fatty Liver
Overweight
Procetofen

Body Weight
Signs and Symptoms
Nicotinic Acids
Digestive System Diseases
Nutrition Disorders
Overnutrition
Niacin

Additional relevant MeSH terms:

Antimetabolites
Hypoglycemic Agents
Molecular Mechanisms of Pharmacological Action
Therapeutic Uses

Antilipemic Agents
Physiological Effects of Drugs
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 16, 2009