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

Sponsor:	Mayo Clinic
Information provided by:	Mayo Clinic
ClinicalTrials.gov Identifier:	NCT00587119

Purpose

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.

Condition	Intervention
Primary Biliary Cirrhosis Autoimmune Hepatitis	Drug: Budesonide

Study Type:	Interventional
Study Design:	Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Open Label Primary Purpose: Treatment
Official Title:	Open-Label Pilot Study Evaluating Oral Budesonide in the Treatment of Patients With Primary Biliary Cirrhosis and Overlap Features of Autoimmune Hepatitis.

Resource links provided by NLM:

Genetics Home Reference related topics: North American Indian childhood cirrhosis progressive familial intrahepatic cholestasis

MedlinePlus related topics: Cirrhosis Hepatitis Hepatitis A

Drug Information available for: Budesonide Hepatitis A Vaccines

U.S. FDA Resources

Further study details as provided by Mayo Clinic:

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. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

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. [ Time Frame: 1 year ] [ Designated as safety issue: Yes ]

Enrollment:	0
Study Start Date:	December 2007
Estimated Study Completion Date:	July 2009
Primary Completion Date:	July 2009 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Experimental: 1 Single arm, active treatment	Drug: Budesonide Oral Budesonide, 3 mg three times daily, will be given for 1 year. Other Name: Entocort

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.

Eligibility

Ages Eligible for Study:	21 Years to 75 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00587119

Sponsors and Collaborators

Mayo Clinic

Investigators

Principal Investigator:

Keith D Lindor, MD

Mayo Clinic

More Information

Additional Information:

Mayo Clinic Clinical Trials This link exits the ClinicalTrials.gov site

No publications provided

Responsible Party:	Dr. Keith D. Lindor / PI, Mayo Clinic Rochester
ClinicalTrials.gov Identifier:	NCT00587119 History of Changes
Other Study ID Numbers:	07-003586, Budesonide
Study First Received:	December 21, 2007
Last Updated:	October 1, 2010
Health Authority:	United States: Institutional Review Board

Keywords provided by Mayo Clinic:

Urso
Budesonide
PBC
overlap AIH
PBC with overlap features of autoimmune hepatitis

Additional relevant MeSH terms:

Liver Cirrhosis, Biliary
Hepatitis
Hepatitis A
Liver Cirrhosis
Fibrosis
Hepatitis, Autoimmune
Cholestasis, Intrahepatic
Cholestasis
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Liver Diseases
Hepatitis, Viral, Human
Virus Diseases
Enterovirus Infections

Picornaviridae Infections
RNA Virus Infections
Pathologic Processes
Hepatitis, Chronic
Autoimmune Diseases
Immune System Diseases
Budesonide
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Anti-Asthmatic Agents
Respiratory System Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on February 12, 2012