Pentoxifylline for Primary Biliary Cirrhosis

Primary Biliary Cirrhosis Clinical Trial

Official title:

A Pilot Study of Pentoxifylline for the Treatment of Primary Biliary Cirrhosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01249092
• Other study ID #: 07-1003
• Status: Completed
• Phase: Phase 2
• First received: November 24, 2010
• Last updated: October 16, 2013
• Start date: November 2010
• Est. completion date: March 2013

Study information

• Verified date: October 2013
• Source: The Cleveland Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: March 2013
• Est. primary completion date: June 2012
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 76 Years

Eligibility

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.

Study Design

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Cirrhosis
• Liver Cirrhosis, Biliary
• Primary Biliary Cirrhosis

Intervention

Drug:
• Pentoxifylline
Patients will take 400mg of pentoxifylline three times daily for a total duration of 6 months.

Locations

Country	Name	City	State
United States	Cleveland Clinic	Cleveland	Ohio

Sponsors (1)

Lead Sponsor	Collaborator
The Cleveland Clinic

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in Serum Alkaline Phosphatase Levels.	Serum alkaline phosphatase levels at entry and at 6 months of therapy with PTX will be measured and compared.	6 months	No
Secondary	Change in Serum Concentration of Tissue Inhibitor Metalloproteinase 1 (TIMP-1) After PTX Therapy.	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.	6 months	No
Secondary	Safety of Therapy in the Pilot Study of PTX Therapy in Patients With PBC Will be Assessed	The number of participants that experienced any severe adverse events will be monitored and recorded.	6 months	Yes