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

The recruitment status of this study is unknown because the information has not been verified recently.
Verified December 2005 by Northwestern University.
Recruitment status was  Recruiting
Sponsor:
Information provided by:
Northwestern University
ClinicalTrials.gov Identifier:
NCT00267670
First received: December 12, 2005
Last updated: February 9, 2006
Last verified: December 2005
  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
Phase 2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Double-Blind
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:
  • To assess the effect of pentoxifylline on serum markers of liver inflammation (ALT) in patients with NASH
  • To assess the effect of pentoxifylline on inflammation and fibrosis by examining liver histology in patients with NASH

Secondary Outcome Measures:
  • To assess the effect of pentoxifylline on cytokine levels (i.e. tumor necrosis factor [TNF]-α, interleukin-6 [IL-6], IL-10) and expression of TNF-alpha receptors (p55 and p75) in patients with NASH
  • To assess the effect of pentoxifylline on adipocyte-derived cytokines, leptin and adiponectin, and its effect on free fatty acid levels in patients with NASH
  • To assess the effect of pentoxifylline on serum markers of oxidative stress (i.e. thiobarbituric acid reactive substances [TBARS] – measure of lipid peroxidation) in patients with NASH
  • To determine the effect of pentoxifylline on serum markers of liver fibrosis (i.e. hyaluronic acid and procollagen III N-peptide [P-IIINP]) and correlate with liver histology

Estimated Enrollment: 30
Study Start Date: March 2005
Estimated Study Completion Date: May 2008
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 Gastroenterol 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

Contacts
Contact: Robin R Smolak, BA 312-503-0623 ext 0623 r-smolak@northwestern.edu
Contact: Mary E Rinella, MD 312-503-4592 ext 4592 m-rinella@northwestern.edu

Locations
United States, Illinois
Northwestern University Recruiting
Chicago, Illinois, United States, 60611
Principal Investigator: Mary E Rinella, MD         
Sub-Investigator: Richard M Green, MD         
Sub-Investigator: Sean WP Koppe, MD         
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):
ClinicalTrials.gov Identifier: NCT00267670     History of Changes
Other Study ID Numbers: IRB # 1347-001, GCRC Protcol #891
Study First Received: December 12, 2005
Last Updated: February 9, 2006
Health Authority: United States: Food and Drug Administration

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

Additional relevant MeSH terms:
Liver Diseases
Fatty Liver
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 July 28, 2014