Low-Dose Oral Methotrexate Versus Colchicine for Primary Biliary Cirrhosis
Low-Dose Oral Methotrexate Versus Colchicine for Primary Biliary Cirrhosis
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.
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.
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