Thalidomide for Decreasing Collagen Biosynthesis in People With Progressive Systemic Sclerosis
Drug: Placebo thalidomide
|Study Design:||Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Treatment
|Official Title:||T Cell Immunity in Collagen Biosynthesis of Scleroderma|
- Collagen mRNA levels in the skin [ Time Frame: Measured at Weeks 16 and 48 ] [ Designated as safety issue: No ]
- In vivo collagen production [ Time Frame: Measured at Weeks 16 and 48 ] [ Designated as safety issue: No ]
- Immune function [ Time Frame: Measured at Weeks 4, 16, and 48 ] [ Designated as safety issue: No ]
- Clinical disease measures [ Time Frame: Measured at Weeks 16 and 48 ] [ Designated as safety issue: No ]
- Hypothalamic-Pituitary-Adrenal (HPA) axis measures [ Time Frame: Measured at Weeks 16 and 48 ] [ Designated as safety issue: No ]
- Safety measures [ Time Frame: Measured at Weeks 4, 16, and 48 ] [ Designated as safety issue: Yes ]
|Study Start Date:||August 2000|
|Study Completion Date:||October 2007|
Participants will receive thalidomide.
Thalidomide at a dose of 50 mg/day. The 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.
Placebo Comparator: 2
Participants will receive placebo thalidomide.
Drug: Placebo thalidomide
Participants will receive placebo thalidomide. The placebo dose will be increased through to Week 6.
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 electrocardiogram, a skin biopsy, and various questionnaires. Outpatient study visits will occur at Weeks 2, 4, 6, 8, 12, 18, 20 and then every 4 weeks until Week 44. Assessments will include measures of immune function, clinical disease, hypothalamic-pituitary-adrenal axis, and safety. Following the Week 48 inpatient visit, thalidomide will be tapered off over a 2-week period for all participants.
Please refer to this study by its ClinicalTrials.gov identifier: NCT00418132
|United States, New York|
|New York University School of Medicine General Clinical Research Center, Bellevue Hospital|
|New York, New York, United States, 10016|
|Principal Investigator:||Stephen J. Oliver, MD||New York University School of Medicine|