Orlistat (Xenical) in the Treatment of Overweight Patients With Nonalcoholic Steatohepatitis (NASH)
Information source: St. Louis University
Information obtained from ClinicalTrials.gov on June 20, 2008
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Fatty Liver; Hepatitis
Intervention: Orlistat (Xenical) (Drug); 1400 kcal diet (30% fat) (Behavioral)
Phase: Phase 4
Status: Completed
Sponsored by: St. Louis University Official(s) and/or principal investigator(s):
Brent A Tetri, MD, Principal Investigator, Affiliation: St. Louis University
Summary
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.
Clinical Details
Official title: Orlistat (Xenical) in the Treatment of Overweight Patients With Nonalcoholic Steatohepatitis (NASH)
Study design: Treatment, Randomized, Open Label, Active Control, Parallel Assignment, Efficacy Study
Primary outcome: 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: BMI,ALT,Serum free fatty acids,HOMA-IR (fasting insulin x fasting glucose/22.4)
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
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
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
Locations and Contacts
Saint Louis University, St. Louis, Missouri 63110, United States
Brooke Army Medical Center, San Antonio, Texas 78234, United States
Additional Information
American Liver Foundation description of NASH NIDDK description of NASH
Starting date: October 2003
Ending date: December 2006
Last updated: November 19, 2007
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