Pentoxifylline in Patients With Nonalcoholic Steatohepatitis

Nonalcoholic Steatohepatitis Clinical Trial

Official title:

Treatment Efficacy of Pentoxifylline in Patients With Nonalcoholic Steatohepatitis: A Double-blind Randomized Placebo Controlled Trial

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00590161
• Other study ID #: R-1196 CWRU CRU
• Status: Completed
• Phase: Phase 2
• First received: December 26, 2007
• Last updated: August 5, 2013
• Start date: December 2006
• Est. completion date: December 2010

Study information

• Verified date: August 2013
• Source: Case Western Reserve University
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 55
• Est. completion date: December 2010
• Est. primary completion date: July 2010
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 70 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Fatty Liver
• Nonalcoholic Steatohepatitis

Intervention

Drug:
• pentoxifylline (PTX)
400 mg PO tid
• placebo
placebo tid

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio
United States	Louis Stokes VA Medical Center	Cleveland	Ohio
United States	Metrohealth Medical Center	Cleveland	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Case Western Reserve University	American College of Gastroenterology

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Histological Improvement of at Least 2 Points in NAFLD Activity Score (NAS) on Liver Biopsy After One Year.	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).	1 year (Baseline liver biopsy done at study entry, and subsequent liver biopsy done after one year of therapy with pentoxifylline or placebo)	No