MOCSLID-CCC

MOCSLID-CCC

• 批准号: 7689312
• 负责人: DONALD P TASHKIN
• 金额: $ 40.13万
• 依托单位: UNIVERSITY OF CALIFORNIA LOS ANGELES
• 依托单位国家: 美国
• 财政年份: 2008
• 资助国家: 美国
• 起止时间: 2008-09-18 至 2013-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7689312
• 关键词: Activities of Daily Living; Acute; Address; Algorithms; Alveolar; Autoantibodies; Baltimore; Biological; Biology; Biopsy; Blood; Blood specimen; Boston; California; Carbon Monoxide; Cause of Death; Chest; Chicago; Clinical; Clinical assessments; Collagen; Collection; Colorado; Computer Assisted; Cyclophosphamide; Data; Data Coordinating Center; Dentistry; Deposition; Diffuse; Diffuse Scleroderma; Disease; District of Columbia; Doctor of Medicine; Doctor of Philosophy; Dose; Double-Blind Method; Dyspnea; Enrollment; Fibrosis; Glass; Health; Housing; Illinois; Immunosuppressive Agents; Inflammation; Inflammatory; Interstitial Lung Diseases; Lead; Letters; Life; Location; Longevity; Los Angeles; Lung; Malignant Neoplasms; Measures; Medical; Medicine; Michigan; Oral; Organ Transplantation; Outcome; Outcome Measure; Participant; Patients; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Pharmacy facility; Physiological; Pilot Projects; Placebos; Plasma; Principal Investigator; Publishing; Pulmonary Fibrosis; Quality Control; Questionnaires; Randomized; Randomized Controlled Clinical Trials; Randomized Controlled Trials; Reporting; Research; Research Infrastructure; Resolution; Resources; Risk; SF-36; Safety; Sampling; San Francisco; Scleroderma; Second Primary Cancers; Self-Administered; Serum; Silver; Skin; South Carolina; Specimen; Surveys; Systemic Scleroderma; Systemic disease; Testing; Texas; Therapeutic immunosuppression; Thick; Time Study; Tissues; Total Lung Capacity; Toxic effect; Universities; University Hospitals; Upper arm; Validation; Virginia; Vital capacity; X-Ray Computed Tomography; abstracting; base; blind; clinical research site; computer design; design; double-blind placebo controlled trial; effective therapy; follow-up; follower of religion Jewish; health related quality of life; improved; indexing; innovation; insight; medical schools; mortality; mycophenolate mofetil; novel; primary outcome; prospective; pulmonary function; repository; respiratory; response; rheumatologist; secondary outcome; skin disorder; tool; treatment duration; treatment effect; treatment response; trial comparing

DESCRIPTION (provided by applicant): Scleroderma (SSc) is a devastating systemic disease in which lung involvement, largely from SSc-related interstitial lung disease (SSc-ILD), has emerged as the leading cause of overall mortality. Developing effective treatments for SSc-ILD will directly impact on both the quality and longevity of life. The original Scleroderma Lung Study (SLS I) was the first randomized controlled trial to demonstrate that SSc-ILD responds to a one year treatment with oral cyclophosphamide (CYC) with improvements in pulmonary function, dyspnea, skin disease, and health-related quality of life (HRQoL). However, the beneficial effects of CYC wane by the end of the 2nd yr, after completing one yr of therapy. Moreover, CYC was associated with significant acute toxicity, and longer therapy is limited by the risk for secondary malignancies. Mycophenolate mofetil (MMF), an immunosuppressive drug approved for organ transplantation, has been administered for up to 2 yrs to patients with SSc-ILD in several uncontrolled pilot studies. MMF was reported to be effective and safe. We hypothesize that the ability to administer MMF for two yrs will result in a better and more sustained improvement in SSc-ILD than can be achieved with one yr of CYC, and with less toxicity. To test this hypothesis, we propose a 5-yr, multi-center (12 clinical centers plus a Data Coordinating Center), parallel-group, double-blind, randomized controlled clinical trial comparing a 2-yr treatment with oral MMF (up to 1.5 g bid, as tolerated) with a 1-yr treatment with oral CYC (2 mg/kg/d for 1 yr followed by placebo MMF for a second yr to maintain the blind) in 150 patients with active SSc-ILD. Three SPECIFIC AIMS are proposed: 1) to determine whether MMF is more effective than CYC over the 2nd yr of a 24-mo period with respect to forced vital capacity as the PRIMARY OUTCOME and overall toxicity; 2) to compare MMF and CYC on the course of total lung capacity, single breath diffusing capacity for carbon monoxide, breathlessness (Mahler Transition Dyspnea Index), several HRQoL measures (SGRQ, SF-36), functional ability (Scleroderma Health Assessment Questionnaire) and skin thickness (modified Rodnam skin scores) as SECONDARY OUTCOMES; and 3) to advance our understanding of the biology and response to treatment of SSc-ILD through the collection and innovative analysis of blood samples and skin biopsies collected serially over time from study participants, the prospective validation of a combined outcome measure of overall treatment effect, and the assessment of the clinical utility (a patient-determined value measure) of treatments with MMF or CYC. (End of Abstract)

描述（由申请人提供）：