Pentoxifylline for Primary Biliary Cirrhosis
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.
|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|
- 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.
- 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.
|Study Start Date:||November 2010|
|Study Completion Date:||March 2013|
|Primary Completion Date:||June 2012 (Final data collection date for primary outcome measure)|
Experimental: Pentoxifylline 400 mg TID
This study is an open label pilot with only one arm.
Patients will take 400mg of pentoxifylline three times daily for a total duration of 6 months.
Please refer to this study by its ClinicalTrials.gov identifier: NCT01249092
|United States, Ohio|
|Cleveland, Ohio, United States, 44195|
|Principal Investigator:||Claudia O. Zein, MD, MSc||The Cleveland Clinic|