SIMVASTATIN IN PAH

本子项目是利用由NIH/NCRR资助的中心赠款提供的资源的众多研究子项目之一。子项目和研究者（PI）可能已经从另一个NIH来源获得了主要资金，因此可以在其他CRISP条目中表示。列出的机构是中心的，不一定是研究者的机构。目前可用的治疗肺动脉高压（PAH）的方法疗效有限，并伴有多种不良反应。他汀类药物最近被证明对血管壁功能具有广泛的作用，而不依赖于降低胆固醇，这将有望对PAH的血管重塑产生有益的影响。动物研究表明辛伐他汀对实验性肺动脉高压有显著的衰减和消退作用。本研究的目的是测试辛伐他汀对PAH患者的疗效和安全性。这是一项为期12周的双盲安慰剂对照试验，辛伐他汀40mg /天，用于临床稳定且已接受FDA批准的波生坦、丙炔醇或曲前列尼常规治疗的原发性肺动脉高压或PAH合并结缔组织疾病患者。主要结果测量是运动耐受性，通过从基线到12周6分钟步行距离的变化来评估。每位受试者总共需要4次访问：筛查、基线、6周和12周。与斯坦福大学合作，总共将招募70名受试者（每组35名患者）。其他疗效参数包括Borg呼吸困难评分、NYHA功能分级和临床恶化时间。研究参与者的安全性将通过收集整个研究过程中的不良事件和实验室测试来密切监测，这些不良事件将在筛查、基线以及2、6和12周进行。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.