Pentoxifylline in Patients With Nonalcoholic Steatohepatitis

August 5, 2013 updated by: Claudia Zein, Case Western Reserve University

Treatment Efficacy of Pentoxifylline in Patients With Nonalcoholic Steatohepatitis: A Double-blind Randomized Placebo Controlled Trial

One third of the population in the United States has nonalcoholic fatty liver disease (NAFLD). Nonalcoholic steatohepatitis (NASH), the progressive form of NAFLD, can lead to cirrhosis.Currently, there is no proven therapy for patients with NASH. The investigators core hypothesis is that therapy of patients with NASH with pentoxifylline (PTX) for one year will result in improvement of biochemical parameters of liver disease and hepatic histology. The focus of this proposal is on the effectiveness of pentoxifylline (PTX) in improving laboratory and tissue parameters of liver disease, parameters of insulin-resistance, and levels of cytokines in patients with NASH.

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Actual)

55

Phase

  • Phase 2

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
    • Ohio
      • Cleveland, Ohio, United States, 44195
        • Cleveland Clinic
      • Cleveland, Ohio, United States, 44109
        • MetroHealth Medical Center
      • Cleveland, Ohio, United States, 44106
        • Louis Stokes VA 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 to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Male and female patients ages 18 to 70 years.
  • Liver biopsy compatible with NASH, including presence of steatosis and necroinflammatory activity on liver biopsy done during the prior 6 months to study enrollment
  • Daily alcohol intake of <30 g for males and <15 g for females;
  • Appropriate exclusion of other liver diseases.
  • Patients with diabetes mellitus type 2 diagnosis as defined by a previous diagnosis of DM and current therapy with antidiabetic agents, or by fulfillment of 1997 American Diabetic Association (ADA) criteria, may be included if they fulfill the following criteria: (i) therapeutic regimen limited to specific oral agents including sulfonylureas (e.g. glipizide and glyburide) and/or biguanides (e.g. metformin); (ii) stable therapeutic regimen as defined by no changes in oral agents for at least 3 months; (iii) Hemoglobin A1C (HgbA1C) < 8.5 %.

Exclusion Criteria:

  • History of past excessive alcohol drinking (as defined above) for a period longer than 2 years at any time in the past 10 years.
  • Current consumption of alcohol >30 g daily for males and >15 g daily for females.
  • Positive testing for hepatitis B surface antigen, hepatitis C virus antibody, or ribonucleic acid (RNA) of hepatitis C virus of deoxyribonucleic acid (DNA) of hepatitis B virus.
  • Patients taking medications known to cause steatosis.
  • Other causes of liver disease suspected by history, family interview, or laboratory testing.
  • Patients with cirrhosis defined by stage 4 fibrosis on liver biopsy, or if the patient shows unequivocal clinical evidence of portal hypertension, such as thrombocytopenia, splenomegaly, or esophageal varices.
  • Patients taking medications of possible benefit in NASH within 3 months prior to the liver biopsy. These medications include Vitamin E, Betaine, S-adenosylmethionine (SAM-e), thiazolidinediones, and acarbose.
  • Patients with diabetes mellitus who are on Insulin therapy.
  • Patients with diabetes mellitus on therapy with thiazolidinediones or alpha-glucosidase inhibitors such as acarbose
  • Hypersensitivity to pentoxifylline or the methylxanthines (caffeine, theophylline, theobromine).
  • History of cerebral or retinal hemorrhage.
  • Other medical comorbidities (such as cardiac, central nervous system, renal, cancer) that would interfere with completion of the study.
  • Patients taking Theophylline or Coumadin because of potential drug-drug interactions with Pentoxifylline.
  • Pregnant or nursing women.

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 Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Pentoxifylline (PTX) 400 mg by mouth (PO) three times daily (TID)
Drug: pentoxifylline (PTX)
400 mg PO tid
Placebo Comparator: 2
Placebo three times daily (TID)
Drug: placebo
placebo tid

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Histological Improvement of at Least 2 Points in NAFLD Activity Score (NAS) on Liver Biopsy After One Year.
Time Frame: 1 year (Baseline liver biopsy done at study entry, and subsequent liver biopsy done after one year of therapy with pentoxifylline or placebo)
The NAFLD Activity Score (NAS) grades NAFLD on liver biopsy based on the individual scoring of steatosis, inflammation and balloning. The NAS is assessed on a scale of 0 to 8 with higher scores indicating more severe disease and lower scores indicating less severe disease. NAS is obtained by adding steatosis(assessed on a scale of 0 to 3), inflammation (assessed on a scale of 0 to 3) and ballooning (assessed on a scale of 0 to 2).
1 year (Baseline liver biopsy done at study entry, and subsequent liver biopsy done after one year of therapy with pentoxifylline or placebo)

Collaborators and Investigators

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

Sponsor

Case Western Reserve University

Collaborators

American College of Gastroenterology

Investigators

  • Principal Investigator: Claudia O Zein, MD, MSc, Case Western Reserve 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

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

December 1, 2006

Primary Completion (Actual)

July 1, 2010

Study Completion (Actual)

December 1, 2010

Study Registration Dates

First Submitted

December 26, 2007

First Submitted That Met QC Criteria

December 26, 2007

First Posted (Estimate)

January 10, 2008

Study Record Updates

Last Update Posted (Estimate)

September 26, 2013

Last Update Submitted That Met QC Criteria

August 5, 2013

Last Verified

August 1, 2013

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • R-1196 CWRU CRU

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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