Pentoxifylline in Patients With Nonalcoholic Steatohepatitis - Full Text View

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. The investigators 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:	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:

MedlinePlus related topics: Liver Diseases

Drug Information available for: Pentoxyl Pentoxifylline

U.S. FDA Resources

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 ]

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 400 mg PO tid	Drug: pentoxifylline 400 mg PO tid
Placebo Comparator: 2 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

Locations

United States, Ohio
Louis Stokes VA Medical Center
Cleveland, Ohio, United States, 44106
University Hospitals Case 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

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):

Zein CO, Yerian LM, Gogate P, Lopez R, Kirwan JP, Feldstein AE, McCullough AJ. Pentoxifylline improves nonalcoholic steatohepatitis: a randomized placebo-controlled trial. Hepatology. 2011 Nov;54(5):1610-9. Epub 2011 Aug 24.

Responsible Party:	Claudia O. Zein, MD, MSc, Case Western Reserve University, Louis Stokes VA Medical Center
ClinicalTrials.gov Identifier:	NCT00590161 History of Changes
Other Study ID Numbers:	R-1196 CWRU CRU
Study First Received:	December 26, 2007
Last Updated:	July 20, 2011
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:

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 February 12, 2012