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

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ClinicalTrials.gov Identifier: NCT00267670
Recruitment Status : Completed
First Posted : December 21, 2005
Results First Posted : September 9, 2014
Last Update Posted : September 9, 2014
Sponsor:
Information provided by (Responsible Party):
Mary Rinella, Northwestern University

Tracking Information
First Submitted Date  ICMJE December 12, 2005
First Posted Date  ICMJE December 21, 2005
Results First Submitted Date  ICMJE January 13, 2011
Results First Posted Date  ICMJE September 9, 2014
Last Update Posted Date September 9, 2014
Study Start Date  ICMJE March 2005
Actual Primary Completion Date September 2009   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: August 27, 2014)
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 ]
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.
Original Primary Outcome Measures  ICMJE
 (submitted: December 20, 2005)
  • 1) To assess the effect of pentoxifylline on serum markers of liver inflammation (ALT) in patients with NASH.
  • 2) To assess the effect of pentoxifylline on inflammation and fibrosis by examining liver histology in patients with NASH
Change History Complete list of historical versions of study NCT00267670 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: August 27, 2014)
  • The Effect of Pentoxifylline on Change in Tumor Necrosis Factor [TNF]-α Levels in Patients With NASH [ Time Frame: one year ]
    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 ]
    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 ]
Original Secondary Outcome Measures  ICMJE
 (submitted: December 20, 2005)
  • 1) To assess the effect of pentoxifylline on cytokine levels (i.e. TNF-, IL-6, IL-10) and expression of TNF-alpha receptors (p55 and p75) in patients with NASH.
  • 2) 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.
  • 3) To assess the effect of pentoxifylline on serum markers of oxidative stress (i.e. TBARS – measure of lipid peroxidation) in patients with NASH.
  • 4) To determine effect of pentoxifylline on serum markers of liver fibrosis (i.e. hyaluronic acid and P-IIINP) and correlate with liver histology.
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Pentoxifylline/Nonalcoholic Steatohepatitis (NASH) Study: The Effect of Pentoxifylline on NASH
Official Title  ICMJE The Effect of Pentoxifylline on Nonalcoholic Steatohepatitis (NASH)
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.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Phase 3
Study Design  ICMJE Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double (Participant, Investigator)
Primary Purpose: Treatment
Condition  ICMJE
  • Nonalcoholic Steatohepatitis
  • Liver Diseases
Intervention  ICMJE
  • Drug: Pentoxifylline
    400mg PO TID
    Other Name: Trental
  • Drug: Placebo
    1 pill PO TID
    Other Name: sugar pill
Study Arms  ICMJE
  • Experimental: Pentoxifylline
    400mg PO TID
    Intervention: Drug: Pentoxifylline
  • Placebo Comparator: Placebo
    1 pill PO TID
    Intervention: Drug: Placebo
Publications * 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.

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: August 27, 2014)
26
Original Enrollment  ICMJE
 (submitted: December 20, 2005)
30
Actual Study Completion Date  ICMJE September 2009
Actual Primary Completion Date September 2009   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 65 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00267670
Other Study ID Numbers  ICMJE IRB # 1347-001
GCRC Protocol #891 ( Other Identifier: Northwestern University Clinical Research Center )
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Mary Rinella, Northwestern University
Study Sponsor  ICMJE Northwestern University
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Mary E Rinella, MD Northwestern University
PRS Account Northwestern University
Verification Date August 2014

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP