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

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Mary Rinella, Northwestern University
ClinicalTrials.gov Identifier:
NCT00267670
First received: December 12, 2005
Last updated: August 27, 2014
Last verified: August 2014
  Purpose

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


Condition Intervention Phase
Nonalcoholic Steatohepatitis
Liver Diseases
Drug: Pentoxifylline
Drug: Placebo
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Investigator)
Primary Purpose: Treatment
Official Title: The Effect of Pentoxifylline on Nonalcoholic Steatohepatitis (NASH)

Resource links provided by NLM:


Further study details as provided by Northwestern University:

Primary Outcome Measures:
  • The Number of Participants With a 30% Reduction in Alanine Aminotransferase (ALT) Treated With Pentoxifylline (PTX) or Placebo for 12 Months. [ Time Frame: baseline and 12 months ] [ Designated as safety issue: No ]
    The primary goal of the study was to determine whether pentoxifylline (PTX) therapy improved serum ALT (> or = 30% change from baseline to month 12) compared to placebo.


Secondary Outcome Measures:
  • The Effect of Pentoxifylline on Change in Tumor Necrosis Factor [TNF]-α Levels in Patients With NASH [ Time Frame: one year ] [ Designated as safety issue: No ]
    The mean change from baseline to month 12 in proinflammatory cytokines (such as TNF-α) and gene expresssion were the secondary endpoints and were analyzed with the same analysis of covariance model and summary statistics specified for the primary endpoint. Differences were regarded as statistically significant when P < 0.05. The results for TNF-α are reported here. Interleukin-6 [IL-6], IL-10) and expression of TNF-alpha Receptors (p55 and p75) had insufficient data for statistical analysis.

  • Change in Serum Leptin Levels in Patients Treated With Pentoxifylline or Placebo for 12 Months [ Time Frame: baseline and one year ] [ Designated as safety issue: No ]
    Values represent changes in leptin from baseline to 12 months in patients treated with pentoxifylline or placebo.

  • Change in Serum Adiponectin Levels in Patients Treated With Pentoxifylline or Placebo for 12 Months [ Time Frame: one year ] [ Designated as safety issue: No ]

Enrollment: 26
Study Start Date: March 2005
Study Completion Date: September 2009
Primary Completion Date: September 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pentoxifylline
400mg PO TID
Drug: Pentoxifylline
400mg PO TID
Other Name: Trental
Placebo Comparator: Placebo
1 pill PO TID
Drug: Placebo
1 pill PO TID
Other Name: sugar pill

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.

  Eligibility

Ages Eligible for Study:   18 Years to 65 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00267670

Locations
United States, Illinois
Northwestern University
Chicago, Illinois, United States, 60611
Sponsors and Collaborators
Northwestern University
Investigators
Principal Investigator: Mary E Rinella, MD Northwestern University
  More Information

No publications provided by Northwestern University

Additional publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Mary Rinella, Mary E. Rinella, MD, Northwestern University, Northwestern University
ClinicalTrials.gov Identifier: NCT00267670     History of Changes
Other Study ID Numbers: IRB # 1347-001, GCRC Protocol #891
Study First Received: December 12, 2005
Results First Received: January 13, 2011
Last Updated: August 27, 2014
Health Authority: United States: Food and Drug Administration

Keywords provided by Northwestern University:
Fatty Liver Disease
Liver
NASH
Nonalcoholic Steatohepatitis
Nonalcoholic Fatty Liver Disease (NAFLD)
Pentoxifylline

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

ClinicalTrials.gov processed this record on October 22, 2014