Thalidomide for the Treatment of Primary Sclerosing Cholangitis (PSC)

This study has been terminated.
(Lack of enrollment)
Sponsor:
Collaborator:
Celgene Corporation
Information provided by:
Mayo Clinic
ClinicalTrials.gov Identifier:
NCT00953615
First received: August 4, 2009
Last updated: January 24, 2012
Last verified: January 2012
  Purpose

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.


Condition Intervention Phase
Primary Sclerosing Cholangitis
Drug: Thalidomide
Phase 2

Study Type: Interventional
Study Design: Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Open Label, Phase II Investigation of Thalidomide for the Treatment of Primary Sclerosing Cholangitis

Resource links provided by NLM:


Further study details as provided by Mayo Clinic:

Primary Outcome Measures:
  • Alkaline Phosphatase, Aspartate Aminotransferase, Alanine Aminotransferase [ Time Frame: 6 months, baseline ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]
    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 [ Time Frame: 6 months ] [ Designated as safety issue: No ]
    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 [ Time Frame: 6 months, baseline ] [ Designated as safety issue: No ]
    Assessment of effect from thalidomide on soluble tumor necrosis factor - alpha compared to baseline values were to be performed at study conclusion.


Enrollment: 1
Study Start Date: April 2006
Study Completion Date: May 2009
Primary Completion Date: May 2009 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 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.
Drug: Thalidomide
Titrate to 400 mg daily for 6 months
Other Name: Thalomid

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.

  Eligibility

Ages Eligible for Study:   18 Years to 72 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00953615

Locations
United States, Minnesota
Mayo Clinic
Rochester, Minnesota, United States, 55905
Sponsors and Collaborators
Mayo Clinic
Celgene Corporation
Investigators
Principal Investigator: Keith D Lindor, MD Mayo Clinic
  More Information

Additional Information:
No publications provided

Responsible Party: Dr. K. Lindor, Mayo Clinic
ClinicalTrials.gov Identifier: NCT00953615     History of Changes
Other Study ID Numbers: 342-06
Study First Received: August 4, 2009
Results First Received: August 8, 2011
Last Updated: January 24, 2012
Health Authority: United States: Food and Drug Administration

Keywords provided by Mayo Clinic:
PSC
Thalidomide

Additional relevant MeSH terms:
Cholangitis
Cholangitis, Sclerosing
Bile Duct Diseases
Biliary Tract Diseases
Digestive System Diseases
Thalidomide
Immunosuppressive Agents
Immunologic Factors
Physiological Effects of Drugs
Pharmacologic Actions
Leprostatic Agents
Anti-Bacterial Agents
Anti-Infective Agents
Therapeutic Uses
Angiogenesis Inhibitors
Angiogenesis Modulating Agents
Growth Substances
Growth Inhibitors
Antineoplastic Agents

ClinicalTrials.gov processed this record on July 28, 2014