Thalidomide for the Treatment of Primary Sclerosing Cholangitis (PSC)

Phase 2

Terminated

Conditions: Primary Sclerosing Cholangitis

Interventions: Drug: Thalidomide

Registration Number: NCT00953615

Lead Sponsor: Mayo Clinic

Brief Summary: 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.

Detailed Description: 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.

Recruitment & Eligibility

Status: TERMINATED

Sex: All

Target Recruitment: 1

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.

Study & Design

Study Type: INTERVENTIONAL

Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Thalidomide	Thalidomide	Participants will be treated with Thalidomide, starting at a dose of 100 mg per day, increasing the dose by 100 mg every 14 days to a maximum of 400 mg per day.

Primary Outcome Measures

Name	Time	Method
Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase	6 months, baseline	The primary outcome was the change in serum liver biochemical parameter levels after 6 months of thalidomide when compared to baseline values. This was to be analyzed using the nonparametric Wilcoxon signed rank test of significance. This was based on the non-normal distribution of serum hepatic biochemical parameters among patients with PSC and the continuous nature of these variables.

Secondary Outcome Measures

Name	Time	Method
Overall Toxicity and Tolerability	6 months	Overall toxicity and tolerability were to be measured by the number of patients with development of neuropathy, increased liver biochemistries, drowsiness, dizziness and orthostatic hypotension.
Mayo Risk Score	6 months	The Mayo Risk Score estimates the survival probability of a patient with primary sclerosing cholangitis based on the following variables: age, bilirubin, albumin, AST and history of variceal bleeding.
Soluble Tumor Necrosis Factor - Alpha	6 months, baseline	Assessment of effect from thalidomide on soluble tumor necrosis factor - alpha compared to baseline values were to be performed at study conclusion.