Pentoxifylline for Primary Biliary Cirrhosis

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Claudia Zein, MD, The Cleveland Clinic
ClinicalTrials.gov Identifier:
NCT01249092
First received: November 24, 2010
Last updated: October 16, 2013
Last verified: October 2013
  Purpose

Primary biliary cirrhosis (PBC) is cholestatic liver disease characterized by progressive destruction of small bile ducts within the liver that can lead to end stage liver disease and all its complications.

Although ursodeoxycholic acid (UDCA) is associated with increased survival in many patients with PBC, there is absence of an adequate response to UDCA in a significant proportion of PBC patients.

Tumor necrosis factor alpha (TNF-alpha) is a cytokine that plays an important role in the pathogenesis of PBC. Other fibrosis biomarkers such as tissue metallo proteinase 1 (TIMP-1) are associated with progression of liver fibrosis in PBC. Pentoxifylline (PTX) is a methylxanthine derivative that inhibits pro-inflammatory cytokines and also has shown anti-fibrotic effects in serum of patients with PBC. Furthermore, PTX has well known clinical and safety profiles. The main hypothesis of this study is that therapy with pentoxifylline (PTX) will result in improvement of liver disease in PBC patients who are incomplete responders to UDCA.

The focus of this proposal is on the effectiveness of PTX in improving laboratory parameters of liver disease and levels of cytokines involved in the pathogenesis of the disease in patients with PBC.


Condition Intervention Phase
Primary Biliary Cirrhosis
Drug: Pentoxifylline
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: A Pilot Study of Pentoxifylline for the Treatment of Primary Biliary Cirrhosis

Resource links provided by NLM:


Further study details as provided by The Cleveland Clinic:

Primary Outcome Measures:
  • Change in Serum Alkaline Phosphatase Levels. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Serum alkaline phosphatase levels at entry and at 6 months of therapy with PTX will be measured and compared.


Secondary Outcome Measures:
  • Change in Serum Concentration of Tissue Inhibitor Metalloproteinase 1 (TIMP-1) After PTX Therapy. [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    Serum concentration of tissue inhibitor metalloproteinase 1 (TIMP-1), a fibrosis biomarker of interest, will be measured and the change in serum levels between entry and end of study will be calculated.

  • Safety of Therapy in the Pilot Study of PTX Therapy in Patients With PBC Will be Assessed [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    The number of participants that experienced any severe adverse events will be monitored and recorded.


Enrollment: 20
Study Start Date: November 2010
Study Completion Date: March 2013
Primary Completion Date: June 2012 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Pentoxifylline 400 mg TID
This study is an open label pilot with only one arm.
Drug: Pentoxifylline
Patients will take 400mg of pentoxifylline three times daily for a total duration of 6 months.

  Eligibility

Ages Eligible for Study:   18 Years to 76 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Male and female patients ages 18 to 76 years.
  • Established diagnosis of PBC based on at least three of the following criteria:

    • Detectable anti-mitochondrial antibodies (AMA)
    • Cholestatic biochemical pattern
    • Liver biopsy compatible with PBC
    • Appropriate exclusion of other liver diseases.
  • Therapy with UDCA at adequate dose (13-15mg/kg/d) for at least six months and evidence of suboptimal response defined by alkaline phosphatase levels that did not normalize and remain elevated by at least 1.5 times the upper limit of normal.
  • No history or present hepatic decompensation (e.g. variceal hemorrhage, encephalopathy, or poorly controlled ascites).

Exclusion Criteria:

  • Findings highly suggestive of liver disease of other etiology.
  • A score >=10 points on the Revised Scoring System for autoimmune hepatitis (AIH), supporting a diagnosis of PBC/AIH overlap.
  • Patients on steroids (systemic), immunosuppressants, or immunomodulatory agents within the previous 6 months.
  • Patients with clinical or laboratory evidence suggestive of decompensated cirrhosis.
  • Hypersensitivity to PTX or the methylxanthines (caffeine, theophylline, theobromine).
  • History of cerebral or retinal hemorrhage.
  • Other medical comorbidities (such as cardiac, renal, cancer) that would interfere with completion of the study.
  • Patients taking Theophylline or Coumadin because of potential drug-drug interactions with PTX. In addition, patients taking low molecular weight heparin preparations.
  • Pregnant or nursing women.
  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: NCT01249092

Locations
United States, Ohio
Cleveland Clinic
Cleveland, Ohio, United States, 44195
Sponsors and Collaborators
The Cleveland Clinic
Investigators
Principal Investigator: Claudia O. Zein, MD, MSc The Cleveland Clinic
  More Information

No publications provided

Responsible Party: Claudia Zein, MD, Staff Physician, Digestive Disease Institute, The Cleveland Clinic
ClinicalTrials.gov Identifier: NCT01249092     History of Changes
Other Study ID Numbers: 07-1003
Study First Received: November 24, 2010
Results First Received: July 31, 2013
Last Updated: October 16, 2013
Health Authority: United States: Food and Drug Administration

Keywords provided by The Cleveland Clinic:
biliary cirrhosis

Additional relevant MeSH terms:
Liver Cirrhosis
Liver Cirrhosis, Biliary
Liver Diseases
Digestive System Diseases
Cholestasis, Intrahepatic
Cholestasis
Bile Duct Diseases
Biliary Tract 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 September 22, 2014