Clinical Trial: Pentoxifylline for Primary Biliary Cirrhosis

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: 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 Summary:
Sponsor: The Cleveland Clinic

Current Primary Outcome: 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: 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.


Current Secondary Outcome:

  • 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:

  • 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


Information By: The Cleveland Clinic

Dates:
Date Received: November 24, 2010
Date Started: November 2010
Date Completion:
Last Updated: October 16, 2013
Last Verified: October 2013