Pentoxifylline/Nonalcoholic Steatohepatitis (NASH) Study: The Effect of Pentoxifylline on NASH

NCT ID: NCT00267670

Last Updated: 2014-09-09

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE2/PHASE3
• Total Enrollment: 26 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2005-03-31
• Study Completion Date: 2009-09-30

Brief Summary

The purpose of this study is to explore the potential benefit of the medication, pentoxifylline, for the treatment of NASH.

Detailed Description

This is an investigational study looking at subjects who have been diagnosed with nonalcoholic steatohepatitis (NASH) or 'fatty liver disease'. There is currently no FDA approved available treatment for NASH. The purpose of this study is to explore the potential benefit of the medication, pentoxifylline, for the treatment of NASH. The effectiveness of this drug will be determined by taking blood samples and a liver biopsy. To determine if there is any effect of the medication, two-thirds of the patients participating in the study will receive pentoxifylline and one-third will receive placebo (sugar pill). Thus, an individual's chance of receiving the drug is 67%. In addition to receiving a study drug (placebo or pentoxifylline) the subjects will be encouraged to achieve modest weight loss (~1-2 lbs/week) via low-fat diet and exercise.

The drug (Pentoxifylline) being studied is not approved for use in people who have NASH. Pentoxifylline is considered experimental in this study. Pentoxifylline has been safely used for the treatment of other medical conditions such as alcohol related liver disease and poor circulation. Pentoxifylline is a pill which is taken three times a day.

Conditions

Nonalcoholic Steatohepatitis; Liver Diseases

Study Design

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

Study Groups

Pentoxifylline

400mg PO TID

Group Type: EXPERIMENTAL

Pentoxifylline

Intervention Type: DRUG

400mg PO TID

Placebo

1 pill PO TID

Group Type: PLACEBO_COMPARATOR

Placebo

Intervention Type: DRUG

1 pill PO TID

Interventions

Pentoxifylline

400mg PO TID

Intervention Type: DRUG

Placebo

1 pill PO TID

Intervention Type: DRUG

Other Intervention Names

Trental; sugar pill

Eligibility Criteria

Inclusion Criteria

1. Subjects must be willing to give written informed consent

2. Diagnosis of steatohepatitis Grade >= 1 (Brunt et al. criteria - Am J Gastroenterology 1999;94(9)2467-74) on biopsy within 6 months prior to entry into protocol

3. No histologic evidence of cirrhosis

4. Persistent ALT elevation (> 1.5 the upper limit normal) over 6 months prior to entry into study

5. Adult subjects 18-65 years of age of any race or gender

6. Compensated liver disease with the following hematologic, biochemical, and serological criteria on entry into protocol:

• Hemoglobin > 11 gm/dL for females and > 12 gm/dL for males
• White blood cell (WBC) > 2.5 K/UL
• Neutrophil count > 1.5 K/UL
• Platelets > 100 K/UL
• Direct bilirubin, within normal limits
• Indirect bilirubin within normal limits (unless non-hepatitis factors such as Gilbert's disease explain indirect bilirubin rise. In such cases total bilirubin must be < 3.0 mg/dL)
• Albumin > 3.2 g/dL
• Serum creatinine within normal limits

7. Hemoglobin A1c (HgbA1c) < 7%

8. Antinuclear antibodies (ANA) < 1:160

9. Anti-smooth muscle Ab negative

10. Serum hepatitis B surface antigen (HepBsAg) negative

11. Serum hepatitis C antibody (HepC Ab) negative

12. Iron/total iron binding capacity (TIBC) ratio (transferrin saturation) < 45%

13. Alpha-1-antitrypsin level within normal limits

14. Ceruloplasmin level within normal limits

15. Negative pregnancy test (females)

16. Concomitant use of lipid lowering agents at study entry will not exclude patients from the study.

Exclusion Criteria

1. Evidence of decompensated cirrhosis

2. Active gastrointestinal (GI) bleeding

3. Renal failure (creatinine clearance < 80 mL/min)

4. Active alcohol or drug abuse

5. Uncontrolled diabetes (HgbA1c > 7)

6. Current treatment with anti-diabetic medications such as thiazolidinediones or metformin (stable doses of sulfonylureas are acceptable)

7. Current treatment with anti-TNF alpha medication (i.e. Remicade or Enbrel)

8. Current treatment with vitamin E

9. Alcohol consumption < 20 g/day (males) or < 10 g/day (females) - assessed by one physician and confirmed with one family member.

10. HIV positive status

11. Any history of cerebral and/or retinal hemorrhage

12. Prior intolerance of pentoxifylline or any other methylxanthine (i.e. caffeine, theophylline, or theobromine)

13. Current use of theophylline

14. Known diagnosis of malignancy

15. Any other conditions which the investigator feels would make the subject unsuitable for enrollment, or could interfere with the subject completing the protocol

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 65 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Northwestern University

OTHER

Sponsor Role: lead

Responsible Party

Mary Rinella

Mary E. Rinella, MD, Northwestern University

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Mary E Rinella, MD

Role: PRINCIPAL_INVESTIGATOR

Northwestern University

Locations

Northwestern University

Chicago, Illinois, United States

Countries

United States

References

Van Wagner LB, Koppe SW, Brunt EM, Gottstein J, Gardikiotes K, Green RM, Rinella ME. Pentoxifylline for the treatment of non-alcoholic steatohepatitis: a randomized controlled trial. Ann Hepatol. 2011 Jul-Sep;10(3):277-86.

Reference Type: DERIVED

PMID: 21677329 (View on PubMed)

Other Identifiers

GCRC Protocol #891

Identifier Type: OTHER

Identifier Source: secondary_id

IRB # 1347-001

Identifier Type: -

Identifier Source: org_study_id