MOCSLID-CCC

基本信息

批准号：
7900384
负责人：
DONALD P TASHKIN
金额：
$ 39.09万
依托单位：
UNIVERSITY OF CALIFORNIA LOS ANGELES
依托单位国家：
美国
项目类别：
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/7900384
关键词：
Activities of Daily Living Acute Address Alveolar Autoantibodies Baltimore Biological Biology Biopsy Blood Blood specimen Boston California Carbon Monoxide Cause of Death Chest Chicago Clinical Clinical assessments Collagen Collection Colorado Computational algorithm 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 Validation Virginia Vital capacity X-Ray Computed Tomography abstracting arm base blind clinical research site 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

项目摘要

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）的一年治疗有反应，并改善了肺功能，呼吸困难，皮肤病和与健康相关的质量的改善生活（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，随机对照临床试验，比较口服MMF的2年治疗1.5 g竞标，可容忍）在150名活跃的SSC-ILD患者中，用口服CYC（2 mg/kg/d进行1年的2 mg/kg/d处理以维持盲人）。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，一氧化碳，呼吸困难（Mahler Transition呼吸困难指数），几种HRQOL测量（SGRQ，SFQ，SFQ，SFQ，SFQ，SFQ，SFQ），功能性能力（Scleroderma Health Consement Consectiment Consectiment Consement询问）的过程中比较MMF和CYC的单呼吸扩散能力（Mahler Transition呼吸困难指数）作为次要结果，皮肤厚度（改良的Rodnam皮肤得分）； 3）通过收集和创新分析血液样本和皮肤活检，随着时间的流逝，从研究参与者串行收集的血液样本和皮肤活检，可以提高我们对生物学的理解和对SSC-ILD治疗的理解，这是对整体治疗效果的预期验证的前瞻性验证，以及使用MMF或CYC处理的临床实用程序（患者确定的价值度量）的评估。（抽象的结尾）