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Sponsors and Collaborators: |
National Center for Research Resources (NCRR) National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) University of Texas |
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Information provided by: | Office of Rare Diseases (ORD) |
ClinicalTrials.gov Identifier: | NCT00004784 |
OBJECTIVES: I. Compare the effects of ursodiol (ursodeoxycholic acid), with and without methotrexate, on pruritus, incapacitation index, and serum markers of activity and severity in patients with primary biliary cirrhosis. II. Compare the effects of these regimens on the development of ascites, encephalopathy, varices (or bleeding from pre-existing varices), histologic liver changes, transplantation, and survival.
III. Compare the toxicity and safety of each regimen.
Condition | Intervention | Phase |
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Liver Cirrhosis, Biliary |
Drug: methotrexate Drug: ursodiol |
Phase III |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Double-Blind |
Estimated Enrollment: | 315 |
Study Start Date: | January 1994 |
PROTOCOL OUTLINE: This is a randomized, double-blind study. Patients are stratified by participating institution and Ludwig histologic stage. All patients are treated with ursodiol (ursodeoxycholic acid, UDCA) for 6 months. If entry criteria continue to be met, patients are randomly assigned to UDCA/methotrexate or UDCA/placebo.
Combination therapy continues for at least 5 years.
Ages Eligible for Study: | 20 Years to 69 Years |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
PROTOCOL ENTRY CRITERIA:
--Disease Characteristics-- The following criteria must be met prior to study entry and ursodiol treatment: Bilirubin less than 3 mg/dL Alkaline phosphatase at least 1.5 times normal limits Albumin at least 3 g/dL The following criteria must be met prior to randomization to Arms I and II: Primary biliary cirrhosis (PBC), i.e.: Cholestatic liver disease for at least 6 months prior to randomization Liver biopsy compatible with PBC within 6 months prior to randomization No biliary obstruction on ultrasound, computerized tomography, or cholangiography The following exclude: Asymptomatic and stage I liver histology (Ludwig classification) Hepatic encephalopathy Ascites Variceal bleeding No liver disease of other etiology, e.g.: Chronic hepatitis B or C Autoimmune chronic active hepatitis Alcoholic liver disease Sclerosing cholangitis Drug-induced liver disease Symptomatic or obstructive gallstones --Prior/Concurrent Therapy-- At least 6 months since the following immunosuppressives: Cyclosporine Tacrolimus Methotrexate At least 3 months since other immunosuppressives, e.g.: Azathioprine Chlorambucil Colchicine Corticosteroids Penicillamine At least 3 months since rifampin --Patient Characteristics-- Life expectancy: No major illness limiting life span Hematopoietic: WBC at least 2500/mm3 Absolute granulocyte count at least 1500/mm3 Platelet count at least 80,000/mm3 Hepatic: See Disease Characteristics Renal: Creatinine clearance at least 60 mL/min Pulmonary: No diffusion capacity or vital capacity less than 50% of predicted Other: Antimitochondrial antibody positive HIV antibody negative No alcoholism within the past 2 years No epilepsy requiring phenytoin No malignancy within the past 5 years other than skin cancer No pregnant women Adequate contraception required of fertile patients
Study ID Numbers: | 199/11873, UTSMC-29205400 |
Study First Received: | February 24, 2000 |
Last Updated: | June 23, 2005 |
ClinicalTrials.gov Identifier: | NCT00004784 History of Changes |
Health Authority: | United States: Federal Government |
cirrhosis gastrointestinal disorders primary biliary cirrhosis rare disease |
Antimetabolites Liver Diseases Biliary Cirrhosis Immunologic Factors Gastrointestinal Diseases Fibrosis Cholestasis Rare Diseases Folate Liver Cirrhosis Folinic Acid Folic Acid Antagonists |
Immunosuppressive Agents Vitamin B9 Primary Biliary Cirrhosis Ursodeoxycholic Acid Folic Acid Cholestasis, Intrahepatic Digestive System Diseases Bile Duct Diseases Biliary Tract Diseases Methotrexate Antirheumatic Agents Liver Cirrhosis, Biliary |
Antimetabolites Liver Diseases Antimetabolites, Antineoplastic Immunologic Factors Molecular Mechanisms of Pharmacological Action Cholestasis Fibrosis Antineoplastic Agents Physiological Effects of Drugs Liver Cirrhosis Reproductive Control Agents Ursodeoxycholic Acid Pathologic Processes Cholestasis, Intrahepatic Cholagogues and Choleretics |
Biliary Tract Diseases Therapeutic Uses Abortifacient Agents Methotrexate Liver Cirrhosis, Biliary Dermatologic Agents Nucleic Acid Synthesis Inhibitors Gastrointestinal Agents Enzyme Inhibitors Abortifacient Agents, Nonsteroidal Folic Acid Antagonists Immunosuppressive Agents Pharmacologic Actions Digestive System Diseases Bile Duct Diseases |