Modulating Effects of Lisinopril on Sildenafil Activity in PAH (MELISSA)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 发起方
- Mayo Clinic
- 入组人数
- 24
- 试验地点
- 1
- 主要终点
- The primary aim of the pilot study is to assess feasibility and tolerability.
研究概览
简要总结
Patients with pulmonary arterial hypertension(PAH) suffer from chronic shortness of breath, and have impaired survival related to progressive right ventricular failure. Abnormal vasoreactivity to nitric oxide(NO) plays a role in the pathophysiology of PAH. Phosphodiesterase Type 5 Inhibitor (PDE5 inhibitors) sildenafil have been shown to be beneficial in PAH, but extent of benefit is variable.
详细描述
The broad aim of this investigation is to determine whether the modulating effect of angiotensin converting enzyme inhibition on vascular smooth muscle responsiveness to the nitric oxide pathway that we have observed in an animal model of Congestive Heart Failure(CHF) can be exploited in humans with PAH. Furthermore, we have identified a group of genes TAO kinase I, IL-10, Rho kinase, Raf1, bile acid coenzyme A and Fmr1 that are modulated by long-acting angiotensin-converting enzyme inhibitor (ACEI) in our animal model, and therefore may also be modulated by ACEI in patients with PAH
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Prospective
入排标准
- 年龄范围
- 18 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18-75
- •World Health Organization (WHO) Group I PAH with prior documentation of peripheral vascular resistance (PVR) > 3 WU and wedge(PCW) 16 or less.
- •WHO Functional Class I-III
- •6 minute walk distance 150-575 meters
- •Women of child bearing potential must have a negative pregnancy test and be using effective contraception
- •Receiving therapy with phosphodiesterase-5 inhibitor for PAH (sildenafil or tadalafil) for at least 3 months and with stable dose for at least 30 days
- •If already receiving therapy with endothelin receptor antagonists must have been on therapy for at least 3 months and on stable dose for at least 30 days
排除标准
- •Allergy or intolerance to captopril or other angiotensin converting enzyme inhibitors
- •Systemic systolic blood pressure less than 100 mm Hg
- •Therapy with prostanoids (iloprost, treprostinil, epoprostenol) within preceding 3 months
- •Pregnant or breast feeding
- •Creatinine > 2.0 mg/dl
- •Potassium > 5.0 meq/dl
- •Unable to provide informed consent
- •TLC or VC <60% predicted
- •Untreated obstructive sleep apnea
- •LVEF < 40%
- •Hb < 10 mg/dL
结局指标
主要结局
The primary aim of the pilot study is to assess feasibility and tolerability.
时间窗: 32 weeks
次要结局
- Demonstrate tolerability of long-acting angiotensin-converting enzyme inhibitor (ACEI) therapy in this patient cohort(32 weeks)
- Demonstrate whether long-acting angiotensin-converting enzyme inhibitor (ACEI) in Pulmonary Arterial Hypertension (PAH) pts on sildenafil modifies regulation of the genes.(32 weeks)
- Demonstrate whether ACEI in PAH pts on sildenafil reduces N-BNP levels, a marker of disease severity(32 weeks)
- Demonstrate whether ACEI in PAH pts on sildenafil has an effect on pulmonary gas exchange parameters (exhaled NO, Dm, Vc, DLCO).(32 weeks)
- Obtain exploratory data regarding whether ACEI in PAH pts on sildenafil improves functional class and 6 minute walk distance.(32 weeks)