ORAL CYCLOPHOSPHAMIDE VS ORAL PLACEBO IN SYSTEMIC SCLEROSIS PULMONARY ALVEOLITIS

口服环磷酰胺与口服安慰剂治疗系统性硬化性肺泡炎的比较

• 批准号: 7379538
• 负责人: ARTHUR C THEODORE
• 金额: $ 0.12万
• 依托单位: BOSTON UNIVERSITY MEDICAL CAMPUS
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7379538
• 关键词: ORAL; CYCLOPHOSPHAMIDE; VS; PLACEBO; SYSTEMIC

This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. The subproject and investigator (PI) may have received primary funding from another NIH source, and thus could be represented in other CRISP entries. The institution listed is for the Center, which is not necessarily the institution for the investigator. Present evidence suggests that pulmonary fibrosis is 40-45% within 10 years of SSc onset. Present evidence suggests that pulmonary fibrosis, which occurs early in the course of SSc, is usually preceded by inflammation which can be detected by examination of cells obtained by bronchoalveolar lavage (BAL). Uncontrolled series suggest that cyclophosphamide (CYC) may stabilize or improve lung function in SSc patients with active alveolitis. We propose to conduct a five-year, 13-center, parallel-group, double-blind, randomized controlled study of oral CYC (1-2 mg/kg/day) versus placebo to assess the efficacy of CYC in stabilizing or improving the course of FVC (as % predicted) in 163 patients with early SSc (within 5 years of clinical disease onset) who are already dyspneic, have a GVC <85% of predicted and exhibit active alveolitis defined as 3% neutrophils or 2% eosinophils in BAL fluid. Secondarily, we will assess the impact of CYC on quality of life (SF36), functional activity (SSc Health Assessment Questionnaire), dyspnea (Mahler Transition Dyspnea Index) and diffusing capacity for carbon monoxide (DLCO) in these patients. Proven methods for analyzing time-oriented data employed by the investigators in previous controlled studies of scleroderma will be used to evaluate whether oral CYC (1-2mg/kg/day) is better than placebo in improving or preventing worsening of FVC and in improving or preventing worsening of quality of life, functional ability, breathlessness and DLCO.

该子项目是利用NIH/NCRR资助的中心赠款提供的资源的许多研究子项目之一。子项目和研究者（PI）可能从另一个NIH来源获得主要资金，因此可以在其他CRISP条目中表示。所列机构为中心，不一定是研究者所在机构。目前的证据表明，肺纤维化是40-45%的SSc发作的10年内。目前的证据表明，肺纤维化，这发生在早期的SSc过程中，通常是由炎症，可以检测到的检查细胞获得支气管肺泡灌洗（BAL）。非对照系列研究表明，环磷酰胺（CYC）可以稳定或改善活动性肺泡炎SSc患者的肺功能。我们计划进行一项为期5年、13个中心、平行组、双盲、随机对照的口服CYC研究（1-2 mg/kg/天）与安慰剂比较，以评估CYC在稳定或改善FVC病程方面的疗效（%预测值）（在临床疾病发作的5年内）已经呼吸困难，具有GVC <预测值的85%，并且表现出活动性肺泡炎（定义为BAL液中3%中性粒细胞或2%嗜酸性粒细胞）的患者。其次，我们将评估CYC对这些患者的生活质量（SF 36）、功能活动（SSc健康评估问卷）、呼吸困难（Mahler过渡期呼吸困难指数）和一氧化碳弥散量（DLCO）的影响。将使用研究者在既往硬皮病对照研究中采用的时间导向数据分析方法，评价口服CYC（1- 2 mg/kg/天）在改善或预防FVC恶化以及改善或预防生活质量、功能能力、呼吸困难和DLCO恶化方面是否优于安慰剂。