NCT00006168

Brief 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.

Trial Health

87
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Timeline
Completed

Started Jan 1994

Longer than P75 for phase_3

Geographic Reach
1 country

12 active sites

Status
completed

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

January 1, 1994

Completed
6.6 years until next milestone

First Submitted

Initial submission to the registry

August 8, 2000

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 9, 2000

Completed
3.6 years until next milestone

Study Completion

Last participant's last visit for all outcomes

March 1, 2004

Completed
Last Updated

January 13, 2010

Status Verified

January 1, 2010

First QC Date

August 8, 2000

Last Update Submit

January 12, 2010

Conditions

Liver Cirrhosis, Biliary

Keywords

primary biliary cirrhosisUrsodeoxycholic acidUDCAMTXHepatologymethotrexateliver

Interventions

MethotrexateDRUG

Eligibility Criteria

Age20 Years - 69 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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.

You may not qualify if:

  • 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.
  • +1 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (12)

Keck School of Medicine at U.S.C.

Los Angeles, California, 90033, United States

Location

U California Medical Center

San Francisco, California, 94143, United States

Location

Yale University School of Medicine

New Haven, Connecticut, 06520-8019, United States

Location

Emory University School of Medicine

Atlanta, Georgia, 30322, United States

Location

Saint Louis University

St Louis, Missouri, 63104, United States

Location

University of Nebraska Medical Center

Omaha, Nebraska, 68198-3285, United States

Location

Cleveland Clinic

Cleveland, Ohio, 44195, United States

Location

Oregon Health Sciences University

Portland, Oregon, 97201, United States

Location

Albert Einstein Medical Center

Philadelphia, Pennsylvania, 19141, United States

Location

UT Southwestern Medical Center at Dallas

Dallas, Texas, 75235-9151, United States

Location

Medical College of Virginia

Richmond, Virginia, 23298-0711, United States

Location

University of Washington Medical Center

Seattle, Washington, 98195, United States

Location

Related Publications (9)

  • Poupon RE, Balkau B, Eschwege E, Poupon R. A multicenter, controlled trial of ursodiol for the treatment of primary biliary cirrhosis. UDCA-PBC Study Group. N Engl J Med. 1991 May 30;324(22):1548-54. doi: 10.1056/NEJM199105303242204.

    PMID: 1674105BACKGROUND

  • Heathcote EJ, Cauch-Dudek K, Walker V, Bailey RJ, Blendis LM, Ghent CN, Michieletti P, Minuk GY, Pappas SC, Scully LJ, et al. The Canadian Multicenter Double-blind Randomized Controlled Trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology. 1994 May;19(5):1149-56.

    PMID: 8175136BACKGROUND

  • Lindor KD, Dickson ER, Baldus WP, Jorgensen RA, Ludwig J, Murtaugh PA, Harrison JM, Wiesner RH, Anderson ML, Lange SM, et al. Ursodeoxycholic acid in the treatment of primary biliary cirrhosis. Gastroenterology. 1994 May;106(5):1284-90. doi: 10.1016/0016-5085(94)90021-3.

    PMID: 8174890BACKGROUND

  • Combes B, Carithers RL Jr, Maddrey WC, Lin D, McDonald MF, Wheeler DE, Eigenbrodt EH, Munoz SJ, Rubin R, Garcia-Tsao G, et al. A randomized, double-blind, placebo-controlled trial of ursodeoxycholic acid in primary biliary cirrhosis. Hepatology. 1995 Sep;22(3):759-66.

    PMID: 7657280BACKGROUND

  • Kaplan MM, Knox TA, Arora SA. Primary biliary cirrhosis treated with low-dose oral pulse methotrexate. Ann Intern Med. 1988 Sep 1;109(5):429-31. doi: 10.7326/0003-4819-109-5-429. No abstract available.

    PMID: 3408057BACKGROUND

  • Kaplan MM. Methotrexate treatment of chronic cholestatic liver diseases: friend or foe? Q J Med. 1989 Aug;72(268):757-61. No abstract available.

    PMID: 2532375BACKGROUND

  • Kaplan MM, Knox TA. Treatment of primary biliary cirrhosis with low-dose weekly methotrexate. Gastroenterology. 1991 Nov;101(5):1332-8. doi: 10.1016/0016-5085(91)90085-y.

    PMID: 1936805BACKGROUND

  • Bergasa NV, Jones A, Kleiner DE, Rabin L, Park Y, Wells MC, Hoofnagle JH. Pilot study of low dose oral methotrexate treatment for primary biliary cirrhosis. Am J Gastroenterol. 1996 Feb;91(2):295-9.

    PMID: 8607496BACKGROUND

  • Buscher HP, Zietzschmann Y, Gerok W. Positive responses to methotrexate and ursodeoxycholic acid in patients with primary biliary cirrhosis responding insufficiently to ursodeoxycholic acid alone. J Hepatol. 1993 Apr;18(1):9-14. doi: 10.1016/s0168-8278(05)80004-2.

    PMID: 8101853BACKGROUND

MeSH Terms

Conditions

Liver Cirrhosis, Biliary

Interventions

Methotrexate

Condition Hierarchy (Ancestors)

Cholestasis, IntrahepaticCholestasisBile Duct DiseasesBiliary Tract DiseasesDigestive System DiseasesLiver DiseasesLiver CirrhosisFibrosisPathologic ProcessesPathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

AminopterinPterinsPteridinesHeterocyclic Compounds, 2-RingHeterocyclic Compounds, Fused-RingHeterocyclic Compounds

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
DOUBLE
Purpose
TREATMENT
Sponsor Type
NIH

Study Record Dates

First Submitted

August 8, 2000

First Posted

August 9, 2000

Study Start

January 1, 1994

Study Completion

March 1, 2004

Last Updated

January 13, 2010

Record last verified: 2010-01

Locations

US(12)