Thalidomide for the Treatment of Primary Sclerosing Cholangitis (PSC)

Open Label, Phase II Investigation of Thalidomide for the Treatment of Primary Sclerosing Cholangitis

The purpose of this study is to determine the safety and benefit of Thalidomide with primary sclerosing cholangitis (PSC). This is a six month study.

At entry, patients will have a complete history and physical, blood tests, ultrasound, and will complete questionnaires. Eligible patients will take Thalidomide 400 mg once a day in the evening. Patients will start a dose of 100 mg per day for two weeks, increasing by 100 mg per day every two weeks to a maximum dose of 400 mg per day for 6 months. Patients will return at 6 months for an evaluation, blood tests and completion of questionnaires. Blood tests will be performed by mailed-in kits at 3 months. Patients will receive weekly phone calls for the first 2 months and bi-monthly thereafter.

Inclusion Criteria:

• Previous diagnosis of primary sclerosing cholangitis as defined by: serum alkaline phosphatase level greater than or equal to 1.5 times the upper limit of normal, negative serum antimitochondrial antibody test, cholangiography diagnostic of PSC without other etiology for biliary obstruction, and liver histology consistent with or diagnostic of PSC
• Patients must give written informed consent.
• Patients must be willing and able to comply with the most recent version of the FDA-mandated System for Thalidomide Education and Prescribing Safety (S.T.E.P.S.®) program.

Exclusion Criteria:

• Pregnant and/or lactating female
• Inability or unwillingness to practice contraceptive measures for the prevention of pregnancy
• History of hypersensitivity reaction to thalidomide
• Inability to provide consent
• Findings suggestive of liver disease of other etiology such as primary biliary cirrhosis, chronic alcoholic liver disease, chronic hepatitis B and C infection, hemochromatosis, Wilson's disease, alpha-1-antitrypsin deficiency, autoimmune hepatitis, and cryptogenic liver disease
• Anticipated need for liver transplantation in one year from decompensated chronic liver disease or recurrent variceal bleeding, spontaneous hepatic encephalopathy, or refractory ascites
• Treatment with tacrolimus, cyclosporine, sirolimus, ursodeoxycholic acid, corticosteroids, colchicine, methotrexate, azathioprine, cyclosporine, chlorambucil, budesonide, pentoxifylline, nicotine, silymarin, vitamin E or pirfenidone in the preceding three months
• History of peripheral neuropathy
• Use of medications with significant drug-drug interactions with thalidomide
• History of Human Immunodeficiency Virus (HIV) positive status or Acquired Immunodeficiency Syndrome (AIDS)
• History of coexistent advanced malignancy
• History of coexistent severe cardiovascular disease
• History of coexistent severe renal disease
• History of current excessive or recent (within 6 months) alcohol use
• Any condition that, in the opinion of the investigators, would interfere with the patient's ability to complete the study safely or successfully
• History of thrombolytic events. Combination use with corticosteroids increases risk of deep vein thrombosis.