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Pentoxifylline for Primary Biliary Cirrhosis

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details. Identifier: NCT01249092
Recruitment Status : Completed
First Posted : November 29, 2010
Results First Posted : December 9, 2013
Last Update Posted : December 9, 2013
Information provided by (Responsible Party):
Claudia Zein, MD, The Cleveland Clinic

Tracking Information
First Submitted Date  ICMJE November 24, 2010
First Posted Date  ICMJE November 29, 2010
Results First Submitted Date  ICMJE July 31, 2013
Results First Posted Date  ICMJE December 9, 2013
Last Update Posted Date December 9, 2013
Study Start Date  ICMJE November 2010
Actual Primary Completion Date June 2012   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: October 16, 2013)
Change in Serum Alkaline Phosphatase Levels. [ Time Frame: 6 months ]
Serum alkaline phosphatase levels at entry and at 6 months of therapy with PTX will be measured and compared.
Original Primary Outcome Measures  ICMJE
 (submitted: November 26, 2010)
Improvement of serum alkaline phosphatase levels. [ Time Frame: 6 months ]
Serum alkaline phosphatase levels at entry, at 3 months, and at 6 months of therapy with PTX will be measured and compared.
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: October 16, 2013)
  • Change in Serum Concentration of Tissue Inhibitor Metalloproteinase 1 (TIMP-1) After PTX Therapy. [ Time Frame: 6 months ]
    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 ]
    The number of participants that experienced any severe adverse events will be monitored and recorded.
Original Secondary Outcome Measures  ICMJE
 (submitted: November 26, 2010)
  • Serum levels of cytokines including TNF-alpha. [ Time Frame: 6 months ]
    Levels of cytokines of interest, including TNF-alpha, at entry and after PTX therapy will be measured and compared.
  • Safety of therapy with PTX in patients with PBC will be assessed [ Time Frame: 6 months ]
    Adverse effects occurring during the study will be compared with the established adverse effects profile of PTX
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
Descriptive Information
Brief Title  ICMJE Pentoxifylline for Primary Biliary Cirrhosis
Official Title  ICMJE A Pilot Study of Pentoxifylline for the Treatment of Primary Biliary Cirrhosis
Brief Summary

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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 2
Study Design  ICMJE Allocation: N/A
Intervention Model: Single Group Assignment
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE Primary Biliary Cirrhosis
Intervention  ICMJE Drug: Pentoxifylline
Patients will take 400mg of pentoxifylline three times daily for a total duration of 6 months.
Study Arms  ICMJE Experimental: Pentoxifylline 400 mg TID
This study is an open label pilot with only one arm.
Intervention: Drug: Pentoxifylline
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by Identifier (NCT Number) in Medline.
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: October 16, 2013)
Original Estimated Enrollment  ICMJE
 (submitted: November 26, 2010)
Actual Study Completion Date  ICMJE March 2013
Actual Primary Completion Date June 2012   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 76 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 NCT01249092
Other Study ID Numbers  ICMJE 07-1003
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party Claudia Zein, MD, The Cleveland Clinic
Study Sponsor  ICMJE The Cleveland Clinic
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Claudia O. Zein, MD, MSc The Cleveland Clinic
PRS Account The Cleveland Clinic
Verification Date October 2013

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