Thalidomide for the Treatment of Primary Sclerosing Cholangitis (PSC)

Primary Sclerosing Cholangitis Clinical Trial

Official title:

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

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT00953615
• Other study ID #: 342-06
• Status: Terminated
• Phase: Phase 2
• First received: August 4, 2009
• Last updated: January 24, 2012
• Start date: April 2006
• Est. completion date: May 2009

Study information

• Verified date: January 2012
• Source: Mayo Clinic
• Contact: n/a
• Is FDA regulated: No
• Health authority: United States: Food and Drug Administration
• Study type: Interventional

Clinical Trial 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.

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 information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: May 2009
• Est. primary completion date: May 2009
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 18 Years to 72 Years

Eligibility

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

Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cholangitis
• Cholangitis, Sclerosing
• Primary Sclerosing Cholangitis

Intervention

Drug:
• Thalidomide
Titrate to 400 mg daily for 6 months

Locations

Country	Name	City	State
United States	Mayo Clinic	Rochester	Minnesota

Sponsors (2)

Lead Sponsor	Collaborator
Mayo Clinic	Celgene Corporation

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	No
Secondary	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	Yes
Secondary	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	No
Secondary	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	No

External Links

•   Mayo Clinic Clinical Trials