Pilot Study of Budesonide for Patients With Primary Sclerosing Cholangitis
Pilot Study of Budesonide for Patients With Primary Sclerosing Cholangitis
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.
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.
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