Back to resultsOral Budesonide in the Treatment of Patients With Primary Biliary Cirrhosis and Overlap Features of Autoimmune Hepatitis (PBC)
Primary Purpose
Primary Biliary Cirrhosis, Autoimmune Hepatitis
Status
Withdrawn
Phase
Not Applicable
Locations
Study Type
Interventional
Intervention
Budesonide
Sponsored by
About this trial
This is an interventional treatment trial for Primary Biliary Cirrhosis focused on measuring Urso, Budesonide, PBC, overlap AIH, PBC with overlap features of autoimmune hepatitis
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.
Sites / Locations
Arms of the Study
Arm 1
Arm Type
Experimental
Arm Label
1
Arm Description
Single arm, active treatment
Outcomes
Primary Outcome Measures
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.
Secondary Outcome Measures
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.
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00587119
Brief Title
Oral Budesonide in the Treatment of Patients With Primary Biliary Cirrhosis and Overlap Features of Autoimmune Hepatitis
Acronym
PBC
Official Title
Open-Label Pilot Study Evaluating Oral Budesonide in the Treatment of Patients With Primary Biliary Cirrhosis and Overlap Features of Autoimmune Hepatitis.
Study Type
Interventional
2. Study Status
Record Verification Date
October 2010
Overall Recruitment Status
Withdrawn
Why Stopped
Lack of enrollment
Study Start Date
December 2007 (undefined)
Primary Completion Date
July 2009 (Actual)
Study Completion Date
July 2009 (Anticipated)
3. Sponsor/Collaborators
Name of the Sponsor
Mayo Clinic
4. Oversight
Data Monitoring Committee
No
5. Study Description
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.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Biliary Cirrhosis, Autoimmune Hepatitis
Keywords
Urso, Budesonide, PBC, overlap AIH, PBC with overlap features of autoimmune hepatitis
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
0 (Actual)
8. Arms, Groups, and Interventions
Arm Title
1
Arm Type
Experimental
Arm Description
Single arm, active treatment
Intervention Type
Drug
Intervention Name(s)
Budesonide
Other Intervention Name(s)
Entocort
Intervention Description
Oral Budesonide, 3 mg three times daily, will be given for 1 year.
Primary Outcome Measure Information:
Title
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
Secondary Outcome Measure Information:
Title
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
10. Eligibility
Sex
All
Minimum Age & Unit of Time
21 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Keith D Lindor, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
12. IPD Sharing Statement
Links:
URL
http://clinicaltrials.mayo.edu
Description
Mayo Clinic Clinical Trials
Learn more about this trial
Oral Budesonide in the Treatment of Patients With Primary Biliary Cirrhosis and Overlap Features of Autoimmune Hepatitis
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