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Pentoxifylline in Patients With Nonalcoholic Steatohepatitis
This study is currently recruiting participants.
Verified by Case Western Reserve University, December 2007
First Received: December 26, 2007   No Changes Posted
Sponsor: Case Western Reserve University
Information provided by: Case Western Reserve University
ClinicalTrials.gov Identifier: NCT00590161
  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. Our core hypothesis is that therapy of patients with NASH with pentoxifylline 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 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
Drug: placebo
Phase II

Study Type: Interventional
Study Design: Treatment, Randomized, Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Placebo Control, Parallel Assignment, Safety/Efficacy Study
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 disease on liver biopsy measured by NAS [ Time Frame: 1 year ] [ Designated as safety issue: No ]

Estimated Enrollment: 64
Study Start Date: December 2006
Estimated Study Completion Date: June 2009
Estimated Primary Completion Date: June 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
1: Experimental
Pentoxifylline 400 mg PO tid
Drug: pentoxifylline
400 mg PO tid
2: Placebo Comparator
Placebo 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 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) 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 RNA of hepatitis C virus of 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
Please refer to this study by its ClinicalTrials.gov identifier: NCT00590161

Contacts
Contact: Claudia O Zein, MD, MSc 216-791-3800 ext 5259 claudia.zein@case.edu
Contact: Beth Bednarchik, RN 216-844-7314 Beth.bednarchik@uhhs.org

Locations
United States, Ohio
Louis Stokes VA Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Claudia O Zein, MD, MSc     216-791-3800 ext 5259     claudia.zein@case.edu    
Contact: Beth Bednarchik, RN     216-844-7314     beth.bednarchik@uhhs.org    
Principal Investigator: Claudia O. Zein, MD, MSc            
University Hospitals Case Medical Center Recruiting
Cleveland, Ohio, United States, 44106
Contact: Beth Bednarchik, RN     216-844-7314     beth.bednarchik@uhhs.org    
Principal Investigator: Claudia O Zein, MD, MSc            
Sub-Investigator: Anthony B. Post, MD            
Sub-Investigator: Pierre M. Gholam, MD            
Cleveland Clinic Recruiting
Cleveland, Ohio, United States, 44195
Contact: Ruth Sargent, LPN     216-444-3126     sargenr@ccf.org    
Principal Investigator: Arthur J McCullough, MD            
Metrohealth Medical Center Not yet recruiting
Cleveland, Ohio, United States, 44109
Sponsors and Collaborators
Case Western Reserve University
Investigators
Principal Investigator: Claudia O Zein, MD, MSc Case Western Reserve University
  More Information

No publications provided

Responsible Party: Case Western Reserve University, Louis Stokes VA Medical Center ( Claudia O. Zein, MD, MSc )
Study ID Numbers: R-1196 CWRU CRU
Study First Received: December 26, 2007
Last Updated: December 26, 2007
ClinicalTrials.gov Identifier: NCT00590161     History of Changes
Health Authority: United States: Food and Drug Administration

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

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

ClinicalTrials.gov processed this record on November 27, 2009