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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT00160407
Recruitment Status : Completed
First Posted : September 12, 2005
Last Update Posted : November 20, 2007
Hoffmann-La Roche
Information provided by:
St. Louis University

Tracking Information
First Submitted Date  ICMJE September 8, 2005
First Posted Date  ICMJE September 12, 2005
Last Update Posted Date November 20, 2007
Study Start Date  ICMJE October 2003
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE
 (submitted: September 8, 2005)
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.
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00160407 on Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: October 12, 2006)
BMI,ALT,Serum free fatty acids,HOMA-IR (fasting insulin x fasting glucose/22.4)
Original Secondary Outcome Measures  ICMJE
 (submitted: September 8, 2005)
  • 1. BMI
  • 2. ALT
  • 3. Serum free fatty acids
  • 4. HOMA-IR (fasting insulin x fasting glucose/22.4)
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Orlistat (Xenical) in the Treatment of Overweight Patients With Nonalcoholic Steatohepatitis (NASH)
Official Title  ICMJE Orlistat (Xenical) in the Treatment of Overweight Patients With Nonalcoholic Steatohepatitis (NASH)
Brief 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.
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 4
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Fatty Liver
  • Hepatitis
Intervention  ICMJE
  • Drug: Orlistat (Xenical)
  • Behavioral: 1400 kcal diet (30% fat)
Study Arms  ICMJE Not Provided
Publications * 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. doi: 10.1002/hep.22575.

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Enrollment  ICMJE
 (submitted: September 8, 2005)
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE December 2006
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
Administrative Information
NCT Number  ICMJE NCT00160407
Other Study ID Numbers  ICMJE 12458
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Not Provided
Study Sponsor  ICMJE St. Louis University
Collaborators  ICMJE Hoffmann-La Roche
Investigators  ICMJE
Principal Investigator: Brent A Tetri, MD St. Louis University
PRS Account St. Louis University
Verification Date November 2007

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP