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Pentoxifylline in Patients With Nonalcoholic Steatohepatitis

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ClinicalTrials.gov Identifier: NCT00590161
Recruitment Status : Completed
First Posted : January 10, 2008
Results First Posted : September 26, 2013
Last Update Posted : September 26, 2013
American College of Gastroenterology
Information provided by (Responsible Party):
Claudia Zein, Case Western Reserve University

Brief Summary:
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.

Condition or disease Intervention/treatment Phase
Nonalcoholic Steatohepatitis Drug: pentoxifylline (PTX) Drug: placebo Phase 2

Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 55 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment Efficacy of Pentoxifylline in Patients With Nonalcoholic Steatohepatitis: A Double-blind Randomized Placebo Controlled Trial
Study Start Date : December 2006
Primary Completion Date : July 2010
Study Completion Date : December 2010

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

Primary Outcome Measures :
  1. 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).

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years to 70 Years   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No

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.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00590161

United States, Ohio
Louis Stokes VA Medical Center
Cleveland, Ohio, United States, 44106
Metrohealth Medical Center
Cleveland, Ohio, United States, 44109
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
Case Western Reserve University
American College of Gastroenterology
Principal Investigator: Claudia O Zein, MD, MSc Case Western Reserve University

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Claudia Zein, Assistant Clinical Professor, Lerner College of Medicine of Case Western Reserve University, Case Western Reserve University
ClinicalTrials.gov Identifier: NCT00590161     History of Changes
Other Study ID Numbers: R-1196 CWRU CRU
First Posted: January 10, 2008    Key Record Dates
Results First Posted: September 26, 2013
Last Update Posted: September 26, 2013
Last Verified: August 2013

Keywords provided by Claudia Zein, Case Western Reserve University:
Fatty Liver
Nonalcoholic fatty liver disease (NALFD)
Nonalcoholic steatohepatitis (NASH)

Additional relevant MeSH terms:
Fatty Liver
Non-alcoholic Fatty Liver Disease
Liver Diseases
Digestive System Diseases
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Platelet Aggregation Inhibitors
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs
Vasodilator Agents
Free Radical Scavengers