Low-Dose Oral Methotrexate Versus Colchicine for Primary Biliary Cirrhosis

Study Overview
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Brief Summary
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OBJECTIVES: I. Compare the efficacy of low-dose oral pulse methotrexate (MTX) and ursodiol versus colchicine and ursodiol in patients with primary biliary cirrhosis (PBC). II. Determine the optimum dose and duration of MTX treatment. III. Investigate the role of fibrogenic cytokines (FC) in PBC pathogenesis and the effect of treatment on FC production.

Detailed Description
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PROTOCOL OUTLINE: This is a randomized, double-blind study. Patients are stratified by prior/concurrent medical management. Patients in the first group are treated with oral methotrexate 3 times a week and a daily oral placebo. Patients in the second group are treated with daily oral colchicine and an oral placebo 3 times a week. Therapy continues for 10 years. Beginning year 2, daily oral ursodiol is administered to all patients. Patients with disease progression are crossed to the alternate group or undergo liver transplantation if clinically indicated.

Official Title
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Phase III Randomized, Double-Blind, Placebo-Controlled Study of Low-Dose Oral Methotrexate Versus Colchicine for Primary Biliary Cirrhosis

Conditions
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Liver Cirrhosis, Biliary

Intervention / Treatment
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* Drug: colchicine
* Drug: methotrexate
* Drug: ursodiol


Participation Criteria
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Eligibility Criteria
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PROTOCOL ENTRY CRITERIA: --Disease Characteristics-- Biopsy proven primary biliary cirrhosis (PBC); Disproportionate increase in alkaline phosphatase; Positive antimitochondrial antibody test OR Symptoms consistent with PBC, e.g.: pruritus, fatigue, malaise, jaundice, elevated bilirubin No clinically advanced PBC, i.e.: bilirubin greater than 10 mg/dL or albumin less than 2.5 g/dL, determined by 2 analyses 10 weeks apart; bleeding esophageal varices or congestive gastropathy; chronic hepatic encephalopathy; chronic ascites --Prior/Concurrent Therapy-- No concurrent drugs associated with chronic liver disease --Patient Characteristics-- Hematopoietic: WBC at least 2500 Platelets at least 100,000 (unless due to hypersplenism); Hematocrit at least 30% Renal: No renal disease that could cause liver dysfunction Other: No history of alcohol abuse; No other medical illness that might cause liver dysfunction, e.g., severe cardiac failure; No pregnant women

Ages Eligible for Study
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Minimum Age: 0 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Intervention/Treatment |
| --- |
|Drug: colchicine|nan|
|Drug: methotrexate|nan|
|Drug: ursodiol|nan|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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cirrhosis, gastrointestinal disorders, primary biliary cirrhosis, rare disease