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）： 硬皮病 (SSc) 是一种毁灭性的全身性疾病，其中肺部受累（主要是由 SSc 相关的间质性肺疾病 (SSc-ILD)）引起，已成为总体死亡的主要原因。开发 SSc-ILD 的有效治疗方法将直接影响生活质量和寿命。最初的硬皮病肺研究 (SLS I) 是第一个随机对照试验，证明 SSc-ILD 对口服环磷酰胺 (CYC) 一年治疗有反应，可改善肺功能、呼吸困难、皮肤病和健康相关生活质量 (HRQoL)。然而，在完成一年的治疗后，CYC 的有益效果在第二年末减弱。此外，CYC 与显着的急性毒性相关，并且较长的治疗受到继发性恶性肿瘤风险的限制。吗替麦考酚酯 (MMF) 是一种被批准用于器官移植的免疫抑制药物，在几项非对照试点研究中，已对 SSc-ILD 患者使用了长达 2 年的药物。据报道 MMF 有效且安全。我们假设，与服用一年的 CYC 相比，服用两年的 MMF 能够更好、更持续地改善 SSc-ILD，并且毒性更小。为了检验这一假设，我们提出了一项为期 5 年、多中心（12 个临床中心加一个数据协调中心）、平行组、双盲、随机对照临床试验，比较 2 年口服 MMF 治疗（每天两次，耐受情况下最高 1.5 g）与 1 年口服 CYC 治疗（2 mg/kg/d，1 年，然后安慰剂 MMF 第二年，以维持 盲）在 150 名活动性 SSc-ILD 患者中进行。提出了三个具体目标： 1) 确定 MMF 在 24 个月周期的第二年是否比 CYC 更有效，以用力肺活量作为主要结果和总体毒性； 2) 比较 MMF 和 CYC 的肺总容量、单次呼吸一氧化碳弥散能力、呼吸困难（马勒过渡性呼吸困难指数）、多项 HRQoL 测量（SGRQ、SF-36）、功能能力（硬皮病健康评估问卷）和皮肤厚度（修正的 Rodnam 皮肤评分）作为次要结果； 3) 通过对研究参与者随时间连续收集的血液样本和皮肤活检进行收集和创新分析，对总体治疗效果的综合结果指标进行前瞻性验证，以及对 MMF 或 CYC 治疗的临床效用（患者确定的价值指标）进行评估，以增进我们对 SSc-ILD 的生物学和治疗反应的理解。 （摘要完）