Ursodiol-Methotrexate for Primary Biliary Cirrhosis

• Status: Completed
• Trial end date: 2004-03-01
• Target enrollment: 0
• Participant gender: All

Summary

The major thrust is to determine whether treatment of patients with Primary Biliary Cirrhosis (PBC) with Ursodiol (Ursodeoxycholic Acid-UDCA) plus methotrexate (MTX) is more effective than treatment with UDCA alone.

• Phase: Phase 3
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
• Treatments: Methotrexate

Criteria

Inclusion Criteria:

• Chronic cholestatic liver disease of at least 6 months' duration.

• Serum alkaline phosphatase levels at least 1.5 times the upper limit of normal prior to treatment with UDCA.

• Serum bilirubin less than 3.0 mg% prior to treatment with UDCA.

• Serum albumin of 3.0 gram% or greater prior to treatment with UDCA.

• Positive antimitochondrial antibody test

• Liver biopsy within the previous 6 months after at least 6 months on UDCA (available for review, and at least 2 cm long if cirrhosis not detected) compatible with the diagnosis of PBC.

• Ultrasound, computed tomography (CT) or cholangiography of the biliary tree which excludes biliary obstruction.

Exclusion Criteria:

• Treatment with immunosuppressive agents including azathioprine, chlorambucil, colchicine, corticosteroids, or d-penicillamine in the preceding 3 months; or with cyclosporine, FK-506 or methotrexate in the preceding 6 months.

• Treatment with rifampin in the preceding 3 months.

• Serum bilirubin of 3.0 mg% or greater.

• Serum albumin less than 3.0 gm%.

• WBC 2,500 mm3; granulocytes 1,500 mm3; platelets 80,000mm3.

• Ascites, hepatic encephalopathy, variceal bleed.

• Findings by clinical, serologic and histologic evidence of liver disease of other etiology (such as chronic hepatitis B or C, autoimmune chronic active hepatitis, alcoholic liver disease, sclerosing cholangitis, drug-induced liver disease, symptomatic or obstructive gallstones).

• Pregnancy, or if not pregnant and in the reproductive period, unwillingness to utilize an adequate form of birth control.

• Age less than 20 or greater than 69 years.

• Epilepsy requiring use of dilantin.

• Malignant disease within the past 5 years (except skin cancer)

• Anti-HIV positive. Major illnesses that could limit life span.

• History of alcoholism during the previous 2 years.

• Creatinine clearance less than 60 ml per minute.

• Severe lung disease, defined as a diffusion capacity or vital capacity of less than 50 percent of predicted.

• Patients who are both asymptomatic and have Stage I histology on liver biopsy (Ludwig classification).