Rapamycin Vs Methotrexate in Diffuse SSc

The recruitment status of this study is unknown because the information has not been verified recently.
Verified October 2005 by University of California, Los Angeles.
Recruitment status was  Active, not recruiting
Sponsor:
Information provided by:
University of California, Los Angeles
ClinicalTrials.gov Identifier:
NCT00241189
First received: October 14, 2005
Last updated: December 28, 2005
Last verified: October 2005
  Purpose

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 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind
Primary Purpose: Treatment
Official Title: A 48-Week, Double-Blind, Randomized, Parallel Phase I/II Study of Oral Rapamycin Versus Methotrexate in Systemic Sclerosis (Scleroderma)

Resource links provided by NLM:


Further study details as provided by University of California, Los Angeles:

Primary Outcome Measures:
  • Adverse events
  • Modified Rodnan Skin thickness score

Secondary Outcome Measures:
  • Forced vital capacity
  • Diffusing capacity (DLCO)
  • Health Assessment Questionnaire-Disability Index
  • Mahler Dyspnea Index
  • Medical Outcomes Questionnaire SF-36
  • Patient global (VAS)
  • Physician global (VAS)
  • % responders in skin score (=>35% decrease from baseline)
  • % responders in HAQ-DI(=>0.22 units decrease from baseline)
  • % responders in FVC (=>10% decrease from baseline)
  • Serum rapamycin levels

Estimated Enrollment: 18
Study Start Date: August 2002
Detailed Description:

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.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Satisfy American College of Rheumatology classification criteria for systemic sclerosis
  • Have skin thickening proximal to the elbows and/or knees (diffuse scleroderma)
  • Cutaneous involvement for less than 5 years from the onset of the first non-Raynaud's manifestation

Exclusion Criteria:

  • Severe intractable malabsorption
  • Chronic debilitation from any underlying disease
  • Off putative disease modifying therapies for one month prior to entry
  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: NCT00241189

Locations
United States, California
Philip Clements, MD
Los Angeles, California, United States, 90095-1670
Sponsors and Collaborators
University of California, Los Angeles
Investigators
Principal Investigator: Philip J Clements, MD, MPH University of California, Los Angeles
  More Information

No publications provided

ClinicalTrials.gov Identifier: NCT00241189     History of Changes
Other Study ID Numbers: UCLA IRB Number: 01-10-045
Study First Received: October 14, 2005
Last Updated: December 28, 2005
Health Authority: United States: Food and Drug Administration

Keywords provided by University of California, Los Angeles:
Systemic sclerosis
Scleroderma
Rapamycin
Methotrexate

Additional relevant MeSH terms:
Sclerosis
Scleroderma, Systemic
Scleroderma, Diffuse
Pathologic Processes
Connective Tissue Diseases
Skin Diseases
Methotrexate
Sirolimus
Everolimus
Abortifacient Agents, Nonsteroidal
Abortifacient Agents
Reproductive Control Agents
Physiological Effects of Drugs
Pharmacologic Actions
Therapeutic Uses
Antimetabolites, Antineoplastic
Antimetabolites
Molecular Mechanisms of Pharmacological Action
Antineoplastic Agents
Dermatologic Agents
Enzyme Inhibitors
Folic Acid Antagonists
Immunosuppressive Agents
Immunologic Factors
Antirheumatic Agents
Nucleic Acid Synthesis Inhibitors
Anti-Bacterial Agents
Anti-Infective Agents
Antibiotics, Antineoplastic
Antifungal Agents

ClinicalTrials.gov processed this record on September 18, 2014