Orlistat (Xenical) in the Treatment of Overweight Patients With Nonalcoholic Steatohepatitis (NASH)

Saint Louis University (SLU)

Status and phase

Completed

Phase 4

Conditions

Fatty Liver

Hepatitis

Treatments

Behavioral: 1400 kcal diet (30% fat)

Drug: Orlistat (Xenical)

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00160407

XEN185

12458

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18+ years old

Volunteers

No Healthy Volunteers

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