- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00418132
Thalidomide for Decreasing Collagen Biosynthesis in People With Progressive Systemic Sclerosis
T Cell Immunity in Collagen Biosynthesis of Scleroderma
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
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.
Study Type
Enrollment (Actual)
Phase
- Phase 1
Contacts and Locations
Study Locations
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New York
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New York, New York, United States, 10016
- New York University School of Medicine General Clinical Research Center, Bellevue Hospital
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Diagnosis of scleroderma
- Agrees to use an effective form of contraception for 1 month prior to study entry, throughout the study, and for 60 days after completing the study
- Positive serum anti-nuclear antibody titer
Exclusion Criteria:
- Systemic sclerosis-like illnesses associated with environmental, ingested, or injected agents or with other connective tissue diseases
Significant existing damage to any of the following internal organs:
- Kidneys, defined as a serum creatinine level greater than 2 mg/dl or renal crisis
- Lungs, defined as needing supplemental oxygen
- Heart, defined as left ventricular ejection fraction less than or equal to 40%
- Gut, defined as pseudo-obstruction or malabsorption requiring total parental nutrition
- Concurrent interventional therapy that might independently influence the outcome of this trial (e.g., D-penicillamine, cyclosporine, interferon-γ, methotrexate, or photophorosis)
- Clinically significant and inadequately medically treated concurrent endocrine, blood, liver, lung, or kidney diseases
- Pregnant
- Recent drug or alcohol abuse
- Documented noncompliance
- Significant psychiatric history
- Therapy with another investigational drug within 4 weeks prior to study entry
- Screening laboratory results exceeding the following limits: hemoglobin level less than 7 gm/dl; white blood cell level less than 3,000/nl; platelet count less than 50/nl; alanine aminotransferase (ALT) level greater than 65 U/L; creatinine level greater than 2 mg/dl
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Double
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: 1
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.
|
Participants will receive placebo thalidomide.
The placebo dose will be increased through to Week 6.
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Collagen mRNA levels in the skin
Time Frame: Measured at Weeks 16 and 48
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Measured at Weeks 16 and 48
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In vivo collagen production
Time Frame: Measured at Weeks 16 and 48
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Measured at Weeks 16 and 48
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Secondary Outcome Measures
Outcome Measure |
Time Frame |
---|---|
Immune function
Time Frame: Measured at Weeks 4, 16, and 48
|
Measured at Weeks 4, 16, and 48
|
Clinical disease measures
Time Frame: Measured at Weeks 16 and 48
|
Measured at Weeks 16 and 48
|
Hypothalamic-Pituitary-Adrenal (HPA) axis measures
Time Frame: Measured at Weeks 16 and 48
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Measured at Weeks 16 and 48
|
Safety measures
Time Frame: Measured at Weeks 4, 16, and 48
|
Measured at Weeks 4, 16, and 48
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Stephen J. Oliver, MD, NYU Langone Health
Study record dates
Study Major Dates
Study Start
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Skin Diseases
- Connective Tissue Diseases
- Scleroderma, Systemic
- Scleroderma, Diffuse
- Physiological Effects of Drugs
- Anti-Infective Agents
- Antineoplastic Agents
- Immunosuppressive Agents
- Immunologic Factors
- Angiogenesis Inhibitors
- Angiogenesis Modulating Agents
- Growth Substances
- Growth Inhibitors
- Anti-Bacterial Agents
- Leprostatic Agents
- Thalidomide
Other Study ID Numbers
- K23AR002187 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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