OBJECTIVES: I. Assess the safety and effectiveness of budesonide in patients with primary sclerosing cholangitis or primary biliary cirrhosis experiencing a suboptimal response to ursodeoxycholic acid. II. Estimate the efficacy of this therapy in these patient groups as a means of evaluating the feasibility of a long-term randomized trial.

Condition	Treatment or Intervention	Phase
Cholangitis, Sclerosing Liver Cirrhosis, Biliary	Drug: budesonide	Phase I

Further Study Details: 

Expected Total Enrollment:  50

PROTOCOL OUTLINE: Patients receive budesonide by mouth 3 times daily for a minimum of 6 months. If liver biochemistries become normal, dosage is reduced to once daily. Treatment discontinues after 1 year.

Ages Eligible for Study:  18 Years   -   70 Years,  Genders Eligible for Study:  Both

Criteria

PROTOCOL ENTRY CRITERIA:

--Disease Characteristics--

Pathologically confirmed primary sclerosing cholangitis (PSC) meeting the following criteria:

• Chronic cholestatic disease for at least 6 months
• Liver biopsy within the past 6 months compatible with the diagnosis of PSC Intra and/or extrahepatic biliary duct obstruction, beading, or narrowing

OR

Pathologically confirmed primary biliary cirrhosis (PBC) that is experiencing suboptimal response to ursodeoxycholic acid and meeting the following criteria:

• Chronic cholestatic liver disease for at least 6 months
• Positive antimitochondrial antibody
• No biliary obstruction by ultrasound, CT, or cholangiography
• Prior liver biopsy compatible with diagnosis of PBC
• Received ursodeoxycholic acid for at least 6 months

--Prior/Concurrent Therapy--

Biologic therapy:

• At least 3 months since prior D-penicillamine
• No planned transplantation for at least 1 year

Chemotherapy:

• At least 3 months (6 months for PBC) since prior cyclosporin, colchicine, azathioprine, or methotrexate
• At least 6 months since prior chlorambucil (PBC only)

Endocrine therapy: At least 3 months (6 months for PBC) since prior corticosteroids

Surgery: No prior intraductal stones or operations on the biliary tree except cholecystectomy (PSC only)

Other:

• At least 3 months since prior pentoxifylline, ursodeoxycholic acid, or nicotine (PSC only)
• At least 6 months since prior chenodeoxycholic acid (PBC only)

--Patient Characteristics--

Life expectancy: At least 3 years

Hematopoietic: Not specified

Hepatic:

• Alkaline phosphatase at least 2 times upper limits of normal
• No chronic hepatitis B infection
• No hepatitis C infection
• No autoimmune hepatitis
• Bilirubin no greater than 4 mg/dL (PBC only)

Cardiovascular: No severe cardiopulmonary disease

Other:

• No concurrent advanced malignancy
• At least 3 months since prior inflammatory bowel disease requiring specific treatment except maintenance therapy (PSC only)
• No anticipated need for transplantation within 1 year
• Not pregnant
• No liver disease of other etiology such as:

Chronic alcoholic liver disease

Hemochromatosis

Wilson's disease

Congenital biliary disease

Cholangiocarcinoma

No recurrent ascending cholangitis requiring hospitalization more than 2 times per year (PSC only)

At least 1 year since prior active peptic ulcer

No recurrent variceal bleeds

No spontaneous encephalopathy

No diuretic-resistant ascites

Study chairs or principal investigators

Keith D. Lindor,  Study Chair,  Mayo Clinic   

Study ID Numbers:  199/13922; MAYOC-41296; MAYOC-DK52344
Record last reviewed:  December 1998
Last Updated:  October 13, 2004
Record first received:  February 24, 2000
ClinicalTrials.gov Identifier:  NCT00004842
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08