Low-Dose Oral Methotrexate Versus Colchicine for Primary Biliary Cirrhosis

Liver Cirrhosis, Biliary Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00004748
• Other study ID #: 199/11664
• Secondary ID: NEMCH-454
• Status: Completed
• Phase: Phase 3
• First received: February 24, 2000
• Last updated: June 23, 2005
• Start date: November 1989

Study information

• Verified date: December 2001
• Source: Office of Rare Diseases (ORD)
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Federal Government
• Study type: Interventional

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 90
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A and older

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double-Blind, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Liver Cirrhosis
• Liver Cirrhosis, Biliary

Intervention

Drug:
• colchicine

• methotrexate

• ursodiol

Locations

Country	Name	City	State
n/a

Sponsors (2)

Lead Sponsor	Collaborator
National Center for Research Resources (NCRR)	Tufts Medical Center