SIMVASTATIN IN PAH

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来源获得了主要资金，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。肺动脉高压（PAH）的现有治疗方法疗效有限，并伴有多种不良反应。最近已证明他汀类药物对血管壁功能具有广泛的作用，不依赖于胆固醇降低，预计这将对PAH的血管重塑产生有益影响。动物研究已经证明辛伐他汀可显著减轻和消退实验性肺动脉高压。本研究的目的是检测辛伐他汀在PAH患者中的疗效和安全性。这是一项在原发性肺动脉高压或结缔组织病相关PAH患者中开展的为期12周、双盲、安慰剂对照试验，辛伐他汀40 mg/天用于临床稳定且已接受FDA批准的波生坦、依前列醇或曲前列尼尔常规治疗的患者。主要结局指标是运动耐量，通过6分钟步行距离从基线到12周的变化进行评估。每例受试者共需要4次访视：筛选、基线、6周和12周。与斯坦福大学合作，共入组70例受试者（每组35例患者）。其他疗效参数将包括博格呼吸困难评分、NYHA心功能分级和至临床恶化的时间。将通过收集整个研究过程中的不良事件和实验室检查（将在筛选、基线和第2、6和12周进行）密切监测研究受试者的安全性。将特别注意三个潜在的问题：肌炎，肝功能异常和妊娠发生。

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. Currently available therapies for pulmonary arterial hypertension (PAH) are of limited efficacy and associated with multiple adverse effects. The statin drugs have recently been shown to possess a broad range of actions on vascular wall function, independent of cholesterol lowering, which would be expected to have a beneficial impact on the vascular remodeling of PAH. Animal studies have documented impressive attenuation and regression of experimental pulmonary hypertension by simvastatin. The objective of this research is to test the efficacy and safety of simvastatin in patients with PAH. This is a 12 week, double-blind, placebo-controlled trial of simvastatin 40 mg/day in patients with either primary pulmonary hypertension or PAH associated with connective tissue disease who are clinically stable and already receiving conventional FDA approved therapy with bosentan, epoprostenol or treprostinil. The primary outcome measure is exercise tolerance as assessed by the change in 6 minute walk distance from baseline to 12 weeks. A total of 4 visits per subject are required: screen, baseline, 6 and 12 weeks. A total of 70 subjects will be enrolled (35 patients per group) in collaboration with Stanford University. Additional efficacy parameters will include Borg dyspnea score, NYHA functional class and time to clinical worsening. Safety of research participants will be monitored closely through collection of adverse events throughout the course of the study and laboratory testing, which will be conducted at screening, baseline and 2, 6 and 12 weeks. Particular attention will be paid to three potential concerns: myositis, liver function abnormalities and pregnancy occurrence.