Orlistat (Xenical) and 1400 kcal diet (30% fat) in Hepatitis and Fatty Liver - Clinical Trials Registry

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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

Interventional

Enrollment

50

Phase

Phase 4

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

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

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years and older (ADULT, OLDER_ADULT)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

Primary Purpose: TREATMENT
Allocation: RANDOMIZED
Interventional Model: PARALLEL
Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
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

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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

St. Louis University

Collaborators

Hoffmann-La Roche

Investigators

Principal Investigator: Brent A Tetri, MD, St. Louis University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General 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.

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

October 1, 2003

Study Completion (ACTUAL)

December 1, 2006

Study Registration Dates

First Submitted

September 8, 2005

First Submitted That Met QC Criteria