Clinical Trial: Thalidomide for Decreasing Collagen Biosynthesis in People With Progressive Systemic Sclerosis

Study Status: Terminated
Recruit Status: Terminated
Study Type: Interventional

Official Title: T Cell Immunity in Collagen Biosynthesis of Scleroderma

Brief Summary: Progressive systemic sclerosis (SSc) is an immune-based disease that causes abnormal connective tissue growth of the skin and internal organs. At this point, there are no effective therapies for treating SSc. Thalidomide is a medication that has been shown to stimulate an immune response that reduces the body's synthesis of collagen, the main component of connective tissue. This study will determine the effectiveness of thalidomide in treating adults with SSc.

Detailed Summary:

Progressive systemic sclerosis (SSc), also known as scleroderma, is a disease of the body's connective tissue. It is characterized by fibrosis of the skin, or formation of scar-like tissue, resulting in progressively increased restriction of joint range of motion. Fibrosis of internal organs also occurs, leading to irregular heart rhythms, acid reflux, and respiratory problems. Unfortunately, no therapies have been developed to effectively treat SSc.

The disease is believed to be an immunological disorder that affects T-helper type 2 (Th2) cells, which stimulate the production of antibodies and interleukin-4 (IL-4), a protein with profibrotic properties. T-helper type 1 (Th1) cells produce interferon-γ (IFN-γ), a protein that prevents fibroblast production of collagen, a primary component of the body's connective tissue. It is possible that shifting the disease's target from the Th2 cells to the Th1 cells may decrease collagen production, and thereby reduce fibrosis. Thalidomide is an immune modulatory drug that has been shown to stimulate production of Th1 cells. This study will evaluate the effectiveness of thalidomide in treating adults with SSc.

Following screening procedures, participants in this 48-week, double-blind study will be randomly assigned to receive placebo or thalidomide at a dose of 50 mg/day. The thalidomide dose will be increased to 100 mg/day at Week 2, then to 200 mg/day at Week 4, and finally to 300 mg/day at Week 6. Participants who experience dose intolerance will immediately switch to the previously tolerated dose. Inpatient hospital visits lasting 2 days will occur at the beginning of the study before starting thalidomide treatment and at Weeks 16 and 48. Assessments and procedures at these visits will include blood and urine collection, a physical exam, a chest X-ray, an electrocardiog
Sponsor: New York University School of Medicine

Current Primary Outcome:

  • Collagen mRNA levels in the skin [ Time Frame: Measured at Weeks 16 and 48 ]
  • In vivo collagen production [ Time Frame: Measured at Weeks 16 and 48 ]


Original Primary Outcome:

  • Measured at Weeks 16 and 48: Collagen mRNA levels in the skin
  • In vivo collagen production


Current Secondary Outcome:

  • Immune function [ Time Frame: Measured at Weeks 4, 16, and 48 ]
  • Clinical disease measures [ Time Frame: Measured at Weeks 16 and 48 ]
  • Hypothalamic-Pituitary-Adrenal (HPA) axis measures [ Time Frame: Measured at Weeks 16 and 48 ]
  • Safety measures [ Time Frame: Measured at Weeks 4, 16, and 48 ]


Original Secondary Outcome:

  • Measured at Weeks 4, 16, and 48: Immune function
  • Measured at Weeks 16 and 48: Clinical disease measures
  • Hypothalamic-Pituitary-Adrenal (HPA) axis measures
  • Safety measures


Information By: New York University School of Medicine

Dates:
Date Received: January 3, 2007
Date Started: August 2000
Date Completion:
Last Updated: March 10, 2016
Last Verified: March 2016