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Sponsored by: |
University of California, Los Angeles |
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Information provided by: | University of California, Los Angeles |
ClinicalTrials.gov Identifier: | NCT00241189 |
This is a study to determine the safety of the immunosuppressive rapamycin in patients with systemic sclerosis with diffuse cutaneous scleroderma. The effects (both good and bad) are being compared to another group of systemic sclerosis patients receiving methotrexate
Condition | Intervention | Phase |
---|---|---|
Systemic Sclerosis |
Drug: rapamycin Drug: methotrexate |
Phase I Phase II |
Study Type: | Interventional |
Study Design: | Treatment, Randomized, Single Blind, Active Control, Parallel Assignment, Safety/Efficacy Study |
Official Title: | A 48-Week, Double-Blind, Randomized, Parallel Phase I/II Study of Oral Rapamycin Versus Methotrexate in Systemic Sclerosis (Scleroderma) |
Estimated Enrollment: | 18 |
Study Start Date: | August 2002 |
Systemic sclerosis (SSc) is a disorder characterized by overproduction and deposition of collagen in the skin and visceral organs, abnormalities of the microcirculation, and autoimmunity. Patients who develop extensive skin thickening (diffuse cutaneous scleroderma) usually do so within the first 5 years. In add tion they are at significant risk of early death, severe involvement of heart (10%), lung (15%) and kidney (15-20%) and loss of functional capacity (moderate to severe disability in about 50% within the first few years). there is as yet no proven cure or treatment which prevents heart, lung or kidney damage, prevents disability or improves survival.
In a previsou study, we treated 10 SSc patients with diffuse cutaneous scleroerma with cyclosporin A (CsA), an agent which suppresses the immune response by reducing production of the pro-inflammatory cytokine, interleukin-2 (IL-2). Significant improvement in skin thickening was noted in 6 of the 10 SSc patients. Unfortuantely, significant reduction in kidney function and/or new onset high blood pressure occurred in 8 of the 10. This frequency and degree of adverse events ina population already at risk of kidney failure and high blood pressure is unacceptable.
More recently an immunosuppressive agent with little kidney toxicity, rapamycin, has been found to block the effects of the same pro-inflammatory cytokine as cyclosporin (IL-2) in transplant patients as part of its immunosuppressive action. Since improvement in skin thickening was seen in our patients who received CsA, we postulate that blocking the effects of IL-2 by rapamycin will also result in improvement in skin thickening in SSc patients with extensive skin thickening. There is growing evidence (from our work and the work of others) that softening thick skin in diffuse SSc is associated with improvement in hand function, joint mobility, arthritis signs, overall functional ability, and survival.
The effectiveness of another immunosuppressive, methotrexate, has been compared to placebo (a dummy) in two SSc studies that had a combined total of 100 patients with estensive skin thickening. In both studies there was a trend to greater softening of the thick scleroderma skin. In one study a greater sense of general well being was also noted in the methotrexate group and in the other study the physician global assessment improved to a greater extent in the methotrexate group. Because there is a suggestion of benefit from methotrexate, the present trial evaluating rapamycin is being compared to methotrexte. During a 48 week period rapamycin and methotrexate will be taken as randomly assigned (9 patients in each arm for a total of 18 patients). Over 48 weeks, the status of these patients' scleroderma will be assessed by simple but validated techniques, including simple palpation of the skin to assess skin thickness; lung function texts, electrocardiogram and chest x-ray to assess heart and lungp; blood pressure and serum creatinine to assess kidney; 3 questionnaires (completed by patients) to assess function, quality of life and shortness of breath; and CBC, chemistries and rapamycin levels to assess safety. Statistical analysis of the courses of the two treatment groups will help us determine whether rapamycin has excessive toxicity and whether there are suggestions of efficacy of rapamycin.
Ages Eligible for Study: | 18 Years and older |
Genders Eligible for Study: | Both |
Accepts Healthy Volunteers: | No |
Inclusion Criteria:
Exclusion Criteria:
United States, California | |
Philip Clements, MD | |
Los Angeles, California, United States, 90095-1670 |
Principal Investigator: | Philip J Clements, MD, MPH | University of California, Los Angeles |
Study ID Numbers: | UCLA IRB Number: 01-10-045 |
Study First Received: | October 14, 2005 |
Last Updated: | December 28, 2005 |
ClinicalTrials.gov Identifier: | NCT00241189 |
Health Authority: | United States: Food and Drug Administration |
Systemic sclerosis Scleroderma Rapamycin Methotrexate |
Folic Acid Sirolimus Skin Diseases Clotrimazole Miconazole |
Tioconazole Connective Tissue Diseases Methotrexate Sclerosis Scleroderma, Systemic |
Antimetabolites Anti-Infective Agents Antimetabolites, Antineoplastic Immunologic Factors Molecular Mechanisms of Pharmacological Action Antineoplastic Agents Physiological Effects of Drugs Enzyme Inhibitors Reproductive Control Agents Antibiotics, Antineoplastic Folic Acid Antagonists |
Abortifacient Agents, Nonsteroidal Immunosuppressive Agents Pharmacologic Actions Anti-Bacterial Agents Pathologic Processes Antifungal Agents Therapeutic Uses Abortifacient Agents Antirheumatic Agents Dermatologic Agents Nucleic Acid Synthesis Inhibitors |