Pentoxifylline in Patients With Nonalcoholic Steatohepatitis

NCT ID: NCT00590161

Last Updated: 2013-09-26

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2
• Total Enrollment: 55 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2006-12-31
• Study Completion Date: 2010-12-31

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.

Conditions

Nonalcoholic Steatohepatitis

Keywords

Fatty Liver; Nonalcoholic fatty liver disease (NALFD); NAFLD; Nonalcoholic steatohepatitis (NASH); NASH; pentoxifylline

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1

Pentoxifylline (PTX) 400 mg by mouth (PO) three times daily (TID)

Group Type: EXPERIMENTAL

pentoxifylline (PTX)

Intervention Type: DRUG

400 mg PO tid

2

Placebo three times daily (TID)

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

placebo tid

Interventions

pentoxifylline (PTX)

400 mg PO tid

Intervention Type: DRUG

placebo

placebo tid

Intervention Type: DRUG

Eligibility 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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

American College of Gastroenterology

OTHER

Sponsor Role: collaborator

Case Western Reserve University

OTHER

Sponsor Role: lead

Responsible Party

Claudia Zein

Assistant Clinical Professor, Lerner College of Medicine of Case Western Reserve University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Claudia O Zein, MD, MSc

Role: PRINCIPAL_INVESTIGATOR

Case Western Reserve University

Locations

Louis Stokes VA Medical Center

Cleveland, Ohio, United States

Metrohealth Medical Center

Cleveland, Ohio, United States

Cleveland Clinic

Cleveland, Ohio, United States

Countries

United States

References

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. doi: 10.1002/hep.24544. Epub 2011 Aug 24.

Reference Type: DERIVED

PMID: 21748765 (View on PubMed)

Other Identifiers

R-1196 CWRU CRU

Identifier Type: -

Identifier Source: org_study_id