Thalidomide for the Treatment of Primary Sclerosing Cholangitis (PSC)

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Primary Sclerosing Cholangitis

Intervention / Treatment
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* Drug: Thalidomide


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 72 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Thalidomide<br>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. | Drug: Thalidomide<br>* Titrate to 400 mg daily for 6 months<br>* Other names: Thalomid;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase | 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. | 6 months, baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Toxicity and Tolerability | 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. | 6 months | 
| Mayo Risk Score | 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. | 6 months | 
| Soluble Tumor Necrosis Factor - Alpha | Assessment of effect from thalidomide on soluble tumor necrosis factor - alpha compared to baseline values were to be performed at study conclusion. | 6 months, baseline | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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PSC, Thalidomide