MOCSLID-CCC

MOCSLID-CCC

• 批准号: 8309281
• 负责人: DONALD P TASHKIN
• 金额: $ 38.92万
• 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 2015-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/8309281
• 关键词: Activities of Daily Living; Acute; Address; Alveolar; Autoantibodies; Biological; Biology; Biopsy; Blood; Blood specimen; Carbon Monoxide; Cause of Death; Chest; Clinical; Clinical assessments; Collagen; Collection; Computational algorithm; Computer Assisted; Cyclophosphamide; Data; Data Coordinating Center; Deposition; Diffuse; Diffuse Scleroderma; Disease; Doctor of Philosophy; Dose; Double-Blind Method; Dyspnea; Enrollment; Fibrosis; Glass; Health; Housing; Immunosuppressive Agents; Inflammation; Inflammatory; Interstitial Lung Diseases; Lead; Letters; Life; Longevity; Lung; Malignant Neoplasms; Measures; Medical; Oral; Organ Transplantation; Outcome; Outcome Measure; Participant; Patients; Peripheral Blood Mononuclear Cell; Pharmaceutical Preparations; Pharmacy facility; Physiological; Pilot Projects; Placebos; Plasma; 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; Scleroderma; Second Primary Cancers; Self-Administered; Serum; Skin; Specimen; Surveys; Systemic Scleroderma; Systemic disease; Testing; Therapeutic immunosuppression; Thick; Time Study; Tissues; Total Lung Capacity; Toxic effect; Validation; Vital capacity; X-Ray Computed Tomography; abstracting; arm; base; blind; clinical research site; design; double-blind placebo controlled trial; effective therapy; follow-up; health related quality of life; improved; indexing; innovation; insight; medical schools; mortality; mycophenolate mofetil; novel; 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）： 硬皮病（SSC）是一种毁灭性的全身性疾病，其中肺部受累主要来自与SSC相关的间质肺疾病（SSC-ILD），已成为总体死亡率的主要原因。为SSC-ILD开发有效的治疗方法将直接影响生活的质量和寿命。原始的硬皮病肺研究（SLS I）是第一个随机对照试验，证明SSC-ILD对口服环磷酰胺（CYC）（CYC）的治疗做出反应，并改善了肺功能，呼吸困难，皮肤病和与健康相关的生活质量质量（HRQOL）。但是，在完成一年的治疗后，CYC减弱的有益影响。此外，CYC与明显的急性毒性有关，较长的治疗受到继发性恶性肿瘤的风险的限制。在几项不受控制的初步研究中，已向患有SSC-ILD的患者提供了多达2年的机器人抑制药物（一种批准器官移植）的免疫抑制药物。据报道，MMF有效且安全。我们假设对两年的MMF进行管理的能力将导致SSC-ILD的更好，更持续的改善，而使用一年的CYC可以实现，并且毒性较小。为了检验这一假设，我们提出了一个5年的多中心（12个临床中心以及一个数据协调中心），平行组，双盲，随机，随机的，随机对照临床试验，与口服MMF（最多可容忍）与1 YR的1 YR（2 mg/kg/kg/d yr）处理的口服MMF（最高1.5 g BID）进行比较，可用于1 YR（可容忍）。 150例活跃SSC-ild患者中的盲人。提出了三个具体目标：1）确定在24-MO时期的第二年中，MMF是否比强迫生命力作为主要结果和总体毒性更有效； 2）在总肺部容量，碳一氧化碳，呼吸困难（Mahler过渡呼吸困难指数），几项HRQOL测量（SGRQ，SFQ，SFQ，SFQ，SFQ，SFQ），功能性能力（Scleroderma Health Consemment Consemment Issemption Consemne and Smirantect）（Modized Rod Speire）下，将MMF和CYC比较MMF和CYC。 3）通过收集和创新分析，对研究参与者的血液样本和皮肤活检的收集和创新分析，对SSC-ILD治疗的理解，并创新分析，从研究参与者中串行收集，对整体治疗效果的共同结果的前瞻性验证以及对临床实用性的评估（患者效用值测量）（一种患者效用值测量）（一种使用MMF或Cyc或Cyc或Cyc或Cyc）的处理方法。 （抽象的结尾）