Overview

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).