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

October 1, 2010 updated by: Mayo Clinic

Open-Label Pilot Study Evaluating Oral Budesonide in the Treatment of Patients With Primary Biliary Cirrhosis and Overlap Features of Autoimmune Hepatitis.

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.

Study Overview

Status

Withdrawn

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Phase

  • Not Applicable

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

19 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: N/A
  • Interventional Model: Single Group Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: 1
Single arm, active treatment
Drug: Budesonide
Oral Budesonide, 3 mg three times daily, will be given for 1 year.
Other Names:
  • Entocort

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Time Frame
The main endpoint will be the percentage of patients with improvement in alkaline phosphatase to less than 1.5 times normal over one year and the percentage of patients with a reduction in their Mayo Risk Score over one year.
Time Frame: 1 year
1 year

Secondary Outcome Measures

Outcome Measure
Time Frame
Effects of UDCA & budesonide on serum levels of alk phos, AST, total bilirubin, albumin, and prothrombin time, Mayo risk score and toxicity and tolerability of the budesonide/UDCA regimen, including effects on bone density.
Time Frame: 1 year
1 year

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Mayo Clinic

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

Helpful Links

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

December 1, 2007

Primary Completion (Actual)

July 1, 2009

Study Completion (Anticipated)

July 1, 2009

Study Registration Dates

First Submitted

December 21, 2007

First Submitted That Met QC Criteria

January 4, 2008

First Posted (Estimate)

January 7, 2008

Study Record Updates

Last Update Posted (Estimate)

October 5, 2010

Last Update Submitted That Met QC Criteria

October 1, 2010

Last Verified

October 1, 2010

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 07-003586
  • Budesonide

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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