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Thalidomide for the Treatment of Primary Sclerosing Cholangitis (PSC)

Primary Purpose

Primary Sclerosing Cholangitis

Status
Terminated
Phase
Phase 2
Locations
United States
Study Type
Interventional
Intervention
Thalidomide
Sponsored by
Mayo Clinic
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Primary Sclerosing Cholangitis focused on measuring PSC, Thalidomide

Eligibility Criteria

18 Years - 72 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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.

Sites / Locations

  • Mayo Clinic

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Thalidomide

Arm Description

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.
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.
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.

Full Information

First Posted
August 4, 2009
Last Updated
January 24, 2012
Sponsor
Mayo Clinic
Collaborators
Celgene Corporation
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1. Study Identification

Unique Protocol Identification Number
NCT00953615
Brief Title
Thalidomide for the Treatment of Primary Sclerosing Cholangitis (PSC)
Official Title
Open Label, Phase II Investigation of Thalidomide for the Treatment of Primary Sclerosing Cholangitis
Study Type
Interventional

2. Study Status

Record Verification Date
January 2012
Overall Recruitment Status
Terminated
Why Stopped
Lack of enrollment
Study Start Date
April 2006 (undefined)
Primary Completion Date
May 2009 (Actual)
Study Completion Date
May 2009 (Actual)

3. Sponsor/Collaborators

Name of the Sponsor
Mayo Clinic
Collaborators
Celgene Corporation

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Sclerosing Cholangitis
Keywords
PSC, Thalidomide

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 2
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Thalidomide
Arm Type
Experimental
Arm Description
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.
Intervention Type
Drug
Intervention Name(s)
Thalidomide
Other Intervention Name(s)
Thalomid
Intervention Description
Titrate to 400 mg daily for 6 months
Primary Outcome Measure Information:
Title
Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase
Description
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.
Time Frame
6 months, baseline
Secondary Outcome Measure Information:
Title
Overall Toxicity and Tolerability
Description
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.
Time Frame
6 months
Title
Mayo Risk Score
Description
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.
Time Frame
6 months
Title
Soluble Tumor Necrosis Factor - Alpha
Description
Assessment of effect from thalidomide on soluble tumor necrosis factor - alpha compared to baseline values were to be performed at study conclusion.
Time Frame
6 months, baseline

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
72 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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.
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Keith D Lindor, MD
Organizational Affiliation
Mayo Clinic
Official's Role
Principal Investigator
Facility Information:
Facility Name
Mayo Clinic
City
Rochester
State/Province
Minnesota
ZIP/Postal Code
55905
Country
United States

12. IPD Sharing Statement

Links:
URL
http://clinicaltrials.mayo.edu
Description
Mayo Clinic Clinical Trials

Learn more about this trial

Thalidomide for the Treatment of Primary Sclerosing Cholangitis (PSC)

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