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

NCT00267670 | Completed Phase 2 Results

• 2 other identifiers: IRB # 1347-001GCRC Protocol #891
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

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

Conditions

Nonalcoholic Steatohepatitis; Liver Diseases

Keywords

Fatty Liver Disease; Liver; NASH; Nonalcoholic Steatohepatitis; Nonalcoholic Fatty Liver Disease (NAFLD); Pentoxifylline

Outcome Measures

Primary Outcomes (1)

• The Number of Participants With a 30% Reduction in Alanine Aminotransferase (ALT) Treated With Pentoxifylline (PTX) or Placebo for 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.

  baseline and 12 months

Secondary Outcomes (3)

• The Effect of Pentoxifylline on Change in Tumor Necrosis Factor [TNF]-α Levels in Patients With NASH

  one year

• Change in Serum Leptin Levels in Patients Treated With Pentoxifylline or Placebo for 12 Months

  baseline and one year

• Change in Serum Adiponectin Levels in Patients Treated With Pentoxifylline or Placebo for 12 Months

  one year

Study Arms (2)

Pentoxifylline

EXPERIMENTAL

400mg PO TID

Drug: Pentoxifylline

Placebo

PLACEBO COMPARATOR

1 pill PO TID

Drug: Placebo

Interventions

Pentoxifylline DRUG

400mg PO TID

Also known as: Trental

Pentoxifylline

Placebo DRUG

1 pill PO TID

Also known as: sugar pill

Placebo

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Subjects must be willing to give written informed consent
• 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
• No histologic evidence of cirrhosis
• Persistent ALT elevation (\> 1.5 the upper limit normal) over 6 months prior to entry into study
• Adult subjects 18-65 years of age of any race or gender
• 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
• Hemoglobin A1c (HgbA1c) \< 7%

You may not qualify if:

• Evidence of decompensated cirrhosis
• Active gastrointestinal (GI) bleeding
• Renal failure (creatinine clearance \< 80 mL/min)
• Active alcohol or drug abuse
• Uncontrolled diabetes (HgbA1c \> 7)
• Current treatment with anti-diabetic medications such as thiazolidinediones or metformin (stable doses of sulfonylureas are acceptable)
• Current treatment with anti-TNF alpha medication (i.e. Remicade or Enbrel)
• Current treatment with vitamin E
• Alcohol consumption \< 20 g/day (males) or \< 10 g/day (females) - assessed by one physician and confirmed with one family member.
• HIV positive status
• Any history of cerebral and/or retinal hemorrhage
• Prior intolerance of pentoxifylline or any other methylxanthine (i.e. caffeine, theophylline, or theobromine)
• Current use of theophylline
• Known diagnosis of malignancy
• Any other conditions which the investigator feels would make the subject unsuitable for enrollment, or could interfere with the subject completing the protocol

Sponsors & Collaborators

• Northwestern University: lead

Study Sites (1)

Northwestern University

Chicago, Illinois, 60611, United States

Location

Related Publications (1)

• 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.

  PMID: 21677329 DERIVED

MeSH Terms

Conditions

Non-alcoholic Fatty Liver Disease; Liver Diseases

Interventions

Pentoxifylline; Sugars

Condition Hierarchy (Ancestors)

Fatty Liver; Digestive System Diseases

Intervention Hierarchy (Ancestors)

Theobromine; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Carbohydrates

Limitations and Caveats

The most significant limitation of this study is the small sample size, thus the lack of statistical significance may be due to low power.

Results Point of Contact

• Title: Mary E. Rinella, MD
• Organization: Northwestern University

m-rinella@northwestern.edu

312-503-4592

Study Officials

• Mary E Rinella, MD

  Northwestern University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Mary E. Rinella, MD, Northwestern University

Study Record Dates

• First Submitted: December 12, 2005
• First Posted: December 21, 2005
• Study Start: March 1, 2005
• Primary Completion: September 1, 2009
• Study Completion: September 1, 2009
• Last Updated: September 9, 2014
• Results First Posted: September 9, 2014

Record last verified: 2014-08

Locations

US (1)