Oral Budesonide in the Treatment of Patients With Primary Biliary Cirrhosis and Overlap Features of Autoimmune Hepatitis

NCT ID: NCT00587119

Last Updated: 2010-10-05

Basic Information

• Recruitment Status: WITHDRAWN
• Clinical Phase: NA
• Study Classification: INTERVENTIONAL
• Study Start Date: 2007-12-31
• Study Completion Date: 2009-07-31

Brief Summary

The purpose of the study is to find out the effects Budesonide, 9 mg daily for one year, has on patients with Primary Biliary Cirrhosis with features of autoimmune hepatitis.

Detailed Description

Pilot Study of Budesonide for Primary Biliary Cirrhosis with overlap features of Autoimmune Hepatitis Primary biliary cirrhosis (PBC) is a chronic liver disease of unknown cause that may result in inflammation and destruction of the bile ducts inside the liver. Over time, cirrhosis and complications of liver failure may develop. Although treatment with ursodiol has been association with a reduction in liver enzymes (blood tests) and a reduction in the progression of the disease, some patients do not respond to ursodiol therapy. Patients with overlap features of Autoimmune Hepatitis (AIH) appear to be at higher risk of developing complications of disease even when on ursodiol. The purpose of this study is to evaluate the effects and safety of Budesonide in PBC with overlap features of AIH. Budesonide has unique effects on the immune system that may be helpful in the treatment of the disease.

Eligible participants will include those patients with a diagnosis of PBC with overlap features of AIH and in whom liver enzymes have not sufficiently improved with ursodiol therapy (the alkaline phosphatase is not less than twice upper normal). At entry all patients will have a history and physical examination, blood tests, bone densitometry and complete quality of life questionnaires. Patients will be prescribed Budesonide 9 mg to take daily for one year in addition to the ursodiol. The medication can be taken with or without food. Blood tests and symptoms diaries will be completed every 3 months. Patients will be contacted by phone to assess tolerance of the medication and any new health problems. At one year, patients will return for a history and physical and repeat blood tests and bone densitometry. Possible side-effects include bone mass loss (bone thinning), diarrhea, indigestion, nausea, joint pains, dizziness, headaches, weight gain and Cushing's syndrome. Other side-effects are possible. The medication and the tests will be billed to the patient or patient's insurance.

Conditions

Primary Biliary Cirrhosis; Autoimmune Hepatitis

Study Design

• Allocation Method: NA
• Intervention Model: SINGLE_GROUP
• Primary Study Purpose: TREATMENT
• Blinding Strategy: NONE

Study Groups

1

Single arm, active treatment

Group Type: EXPERIMENTAL

Budesonide

Intervention Type: DRUG

Oral Budesonide, 3 mg three times daily, will be given for 1 year.

Interventions

Budesonide

Oral Budesonide, 3 mg three times daily, will be given for 1 year.

Intervention Type: DRUG

Other Intervention Names

Entocort

Eligibility Criteria

Inclusion Criteria

• Chronic cholestatic liver disease for greater than 6 months with alkaline phosphatase levels greater than 2 times the upper limit of normal.
• Positive AMA titer 1:40 or AMA > 1.0 U.
• Liver histology in the past (available for review) with features consistent with or diagnostic of PBC
• Ultrasound, computed tomography (CT), or cholangiography of the biliary tree which excludes biliary obstruction.
• The diagnosis of AIH necessary for evaluation of PBC-AIH overlap syndrome will be based on the revised International Autoimmune Hepatitis Group (IAHG) Scoring System.

Exclusion Criteria

• Patients with other serious coexistent conditions such as pre-existing advanced malignancy or severe cardiopulmonary disease which would be expected to limit their expectancy to less than three years.
• Patients unable to provide informed consent.
• Treatment with methotrexate, corticosteroids, azathioprine, chlorambucil, cyclosporin, penicillamine, colchicine or chenodeoxycholic acid in the preceding three months.
• Anticipated need for transplantation in one year (Mayo survival model <80% one-year survival without transplant).
• Liver biopsy revealing stage IV disease.
• Evidence of portal hypertension such as esophageal varices, portal gastropathy, ascites or hepatic encephalopathy.
• Known history of portal vein thrombosis.
• Evidence of osteoporosis.
• Serum bilirubin >4 mg/dl.
• Age less than 21 years of age or greater than 75 years of age.
• Pregnancy.
• Breast-feeding.
• Active drug or alcohol use.
• Findings highly suggestive of liver disease of other etiology such as chronic alcoholic liver disease, chronic hepatitis B or C infection, hemochromatosis, Wilson's disease, 1-antitrypsin deficiency, non-alcoholic steatohepatitis or sclerosing cholangitis.
• Serum creatinine over 2.0 mg/dl.
• History of documented active peptic ulcer disease in preceding year.

• Minimum Eligible Age: 21 Years
• Maximum Eligible Age: 75 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Mayo Clinic

OTHER

Sponsor Role: lead

Responsible Party

Mayo Clinic Rochester

Principal Investigators

Keith D Lindor, MD

Role: PRINCIPAL_INVESTIGATOR

Mayo Clinic

Other Identifiers

Budesonide

Identifier Type: -

Identifier Source: secondary_id

07-003586

Identifier Type: -

Identifier Source: org_study_id