Pentoxifylline for Primary Biliary Cirrhosis

NCT01249092 | Completed Phase 2 Results DMC

• 1 other identifier: 07-1003
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Biliary Cirrhosis

Keywords

biliary cirrhosis

Outcome Measures

Primary Outcomes (1)

• 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

Secondary Outcomes (2)

• Change in Serum Concentration of Tissue Inhibitor Metalloproteinase 1 (TIMP-1) After PTX Therapy.

  6 months

• Safety of Therapy in the Pilot Study of PTX Therapy in Patients With PBC Will be Assessed

  6 months

Study Arms (1)

Pentoxifylline 400 mg TID

EXPERIMENTAL

This study is an open label pilot with only one arm.

Drug: Pentoxifylline

Interventions

Pentoxifylline DRUG

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

Pentoxifylline 400 mg TID

Eligibility Criteria

• Age: 18 Years - 76 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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
• 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).

You may not qualify if:

• 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.

Sponsors & Collaborators

• The Cleveland Clinic: lead

Study Sites (1)

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

Pentoxifylline

Condition Hierarchy (Ancestors)

Cholestasis, Intrahepatic; Cholestasis; Bile Duct Diseases; Biliary Tract Diseases; Digestive System Diseases; Liver Diseases; Liver Cirrhosis; Fibrosis; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Theobromine; Xanthines; Purinones; Purines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

Our study was a small open label pilot completed with no technical problems. The information generated will be useful in designing future larger studies. The main limitation is that PBC is a rare disease which resulted in prolonged enrollment phase.

Results Point of Contact

• Title: Claudia O. Zein, MD
• Organization: Cleveland Clinic

zeinc@ccf.org

216-444-0421

Study Officials

• Claudia O. Zein, MD, MSc

  The Cleveland Clinic

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Staff Physician, Digestive Disease Institute

Study Record Dates

• First Submitted: November 24, 2010
• First Posted: November 29, 2010
• Study Start: November 1, 2010
• Primary Completion: June 1, 2012
• Study Completion: March 1, 2013
• Last Updated: December 9, 2013
• Results First Posted: December 9, 2013

Record last verified: 2013-10

Locations

US (1)