Pentoxifylline in Patients With Nonalcoholic Steatohepatitis

This study has been completed.
Sponsor:
Collaborator:
American College of Gastroenterology
Information provided by (Responsible Party):
Claudia Zein, Case Western Reserve University
ClinicalTrials.gov Identifier:
NCT00590161
First received: December 26, 2007
Last updated: August 5, 2013
Last verified: August 2013
  Purpose

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 Intervention Phase
Nonalcoholic Steatohepatitis
Drug: pentoxifylline (PTX)
Drug: placebo
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Treatment Efficacy of Pentoxifylline in Patients With Nonalcoholic Steatohepatitis: A Double-blind Randomized Placebo Controlled Trial

Resource links provided by NLM:


Further study details as provided by Case Western Reserve University:

Primary Outcome Measures:
  • 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) ] [ Designated as safety issue: No ]
    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).


Enrollment: 55
Study Start Date: December 2006
Study Completion Date: December 2010
Primary Completion Date: July 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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

  Eligibility

Ages Eligible for Study:   18 Years to 70 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00590161

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

No publications provided by Case Western Reserve University

Additional 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
Study First Received: December 26, 2007
Results First Received: March 7, 2012
Last Updated: August 5, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by Case Western Reserve University:
Fatty Liver
Nonalcoholic fatty liver disease (NALFD)
NAFLD
Nonalcoholic steatohepatitis (NASH)
NASH
pentoxifylline

Additional relevant MeSH terms:
Fatty Liver
Liver Diseases
Digestive System Diseases
Pentoxifylline
Phosphodiesterase Inhibitors
Enzyme Inhibitors
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Platelet Aggregation Inhibitors
Hematologic Agents
Therapeutic Uses
Radiation-Protective Agents
Protective Agents
Physiological Effects of Drugs
Vasodilator Agents
Cardiovascular Agents
Free Radical Scavengers
Antioxidants

ClinicalTrials.gov processed this record on July 26, 2014