Pilot Study of Budesonide for Patients With Primary Sclerosing Cholangitis

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