Orlistat (Xenical) in the Treatment of Overweight Patients With Nonalcoholic Steatohepatitis (NASH) - Full Text View

Sponsor:	St. Louis University
Collaborator:	Hoffmann-La Roche
Information provided by:	St. Louis University
ClinicalTrials.gov Identifier:	NCT00160407

Purpose

The purpose of this study is to determine if orlistat (Xenical) therapy in overweight patients with NASH leads to enhanced weight loss over time, with subsequent improvement in the underlying necroinflammatory and fibrotic changes that are typical of NASH.

Condition	Intervention	Phase
Fatty Liver Hepatitis	Drug: Orlistat (Xenical) Behavioral: 1400 kcal diet (30% fat)	Phase IV

Study Type:	Interventional
Study Design:	Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Official Title:	Orlistat (Xenical) in the Treatment of Overweight Patients With Nonalcoholic Steatohepatitis (NASH)

Resource links provided by NLM:

MedlinePlus related topics: Diets Hepatitis Weight Control

Drug Information available for: Orlistat

U.S. FDA Resources

Further study details as provided by St. Louis University:

Primary Outcome Measures:

The primary endpoint is weight loss leading to improvement in the global necroinflammatory and fibrosis scores on liver biopsies. A change of one point in the necroinflammatory grade or fibrosis stage will be considered statistically significant.

Secondary Outcome Measures:

BMI,ALT,Serum free fatty acids,HOMA-IR (fasting insulin x fasting glucose/22.4)

Estimated Enrollment:	50
Study Start Date:	October 2003
Study Completion Date:	December 2006

Detailed Description:

Previous studies have suggested that steady weight loss over time will result in improvement in aminotransferases, and more importantly, underlying histopathology in patients with NASH. A total of 50 biopsy-proven NASH patients will be enrolled in a prospective, randomized fashion. Twenty-five patients have been enrolled at the primary study site at Saint Louis University. Recruitment of the next 25 patients is taking place at a study subsite at Brooke Army Medical Center in San Antonio, Texas.

This will be an open-label study comparing an established weight loss program (1400-calorie diet with 30% fat) plus daily vitamin E (800 IU) and a daily multivitamin to the same weight loss program, daily vitamin E (800 IU) and multivitamin, plus orlistat (120 mg), three times daily for 36 weeks.

Data to be collected from prospective patients includes demographic information, such as age, sex, past medical history, medications, height and weight. Biochemical data to be collected from prospective patients includes liver enzymes, measures of insulin resistance to include, insulin levels, lipid panel, hemoglobin A1C, free fatty acids, complete blood count, coagulation studies, and vitamin E levels. Blood will also be collected and stored for markers of inflammation and fibrosis, such as C reactive protein and TNF-alpha. A liver biopsy will be obtained at the completion of the study for both histopathologic analysis and RNA analysis.

Eligibility

Ages Eligible for Study:	18 Years and older
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Liver biopsy obtained no more than 24 months before randomization with a pathology report confirming that the histological diagnosis is consistent with NASH
Compensated liver disease with the following laboratory parameters at the entry visit:
- Hemoglobin values of greater than or equal to 12 gm/dl for females or 13 gm/dl for males
- WBC count > 3,000/mm3
- Neutrophil count > 1,500/mm3
- Platelets > 70,000/mm3
- Albumin >3.0 g/dl
Serum creatinine <1.4mg/dl
Ability to give informed consent
Alanine aminotransferase (ALT) greater than or equal to 40 U/L
BMI > or equal to 27 kg/m2
Patients who receive orlistat must agree to participate in Xenicare, a free dietary counseling program provided by Roche (sponsor)

Exclusion Criteria:

Any cause for chronic liver disease other than NASH
Evidence of decompensated liver disease such as a history of or presence of ascites, bleeding varices, or spontaneous encephalopathy
History of alcohol consumption of greater than 20 grams per day in the past 2 years
Prior surgical procedures to include gastroplasty, jejunoileal or jejunocolic bypass
TPN within the past 6 months
History of prior organ transplantation
Concurrent enrollment in other experimental treatment protocols
Use of ursodeoxycholic acid, rosiglitazone, pioglitazone, or metformin within the 6-month period before enrollment
Women who are pregnant or breast-feeding

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00160407

Locations

United States, Missouri
Saint Louis University
St. Louis, Missouri, United States, 63110
United States, Texas
Brooke Army Medical Center
San Antonio, Texas, United States, 78234

Sponsors and Collaborators

St. Louis University

Hoffmann-La Roche

Investigators

Principal Investigator:

Brent A Tetri, MD

St. Louis University

More Information

Additional Information:

American Liver Foundation description of NASH This link exits the ClinicalTrials.gov site

NIDDK description of NASH This link exits the ClinicalTrials.gov site

No publications provided by St. Louis University

Additional publications automatically indexed to this study by National Clinical Trials Identifier (NCT ID):

Harrison SA, Fecht W, Brunt EM, Neuschwander-Tetri BA. Orlistat for overweight subjects with nonalcoholic steatohepatitis: A randomized, prospective trial. Hepatology. 2009 Jan;49(1):80-6.

Study ID Numbers:	12458, XEN185
Study First Received:	September 8, 2005
Last Updated:	November 19, 2007
ClinicalTrials.gov Identifier:	NCT00160407 History of Changes
Health Authority:	United States: Institutional Review Board

Keywords provided by St. Louis University:

nonalcoholic steatohepatitis
enzyme inhibitors
lipase
obesity
insulin resistance

Additional relevant MeSH terms:

Liver Diseases
Molecular Mechanisms of Pharmacological Action
Fatty Liver
Overweight
Enzyme Inhibitors
Pharmacologic Actions
Hepatitis

Body Weight
Signs and Symptoms
Anti-Obesity Agents
Orlistat
Digestive System Diseases
Therapeutic Uses
Central Nervous System Agents

ClinicalTrials.gov processed this record on February 08, 2010