Impact of Blocked Cysteinyl Leukotriene Pathway on Endothelial Function in Patients With Obstructive Sleep Apnea Syndrome: Multicenter Randomized Placebo Controlled Crossover Trial
试验速览
- 阶段
- 3 期
- 状态
- 终止
- 发起方
- 入组人数
- 1
- 试验地点
- 4
- 主要终点
- Change in FMD of the brachial artery between the beginning and end of each treatment period (Montelukast and placebo), expressed as absolute value (FMD unit is %) and measured in a standardized manner.
研究概览
简要总结
This study compares the effect of Montelukast vs Placebo on Flow Mediated Dilatation of the Brachial Artery (FMD) in patients with obstructive sleep apnea syndrome.
详细描述
Obstructive Sleep Apnea Syndrome (OSAS) induces low-grade systemic and vascular inflammation, including activation of the leukotriene pathway.
In apneic patients, the urinary excretion of LTE4, a systemic marker of CysLT pathway activation, is increased in relation to the severity of OSAS and it's an independent predictor of cardiovascular risk event occurring at 10 years.
Montelukast is a CysLT1 receptor antagonist. By blocking CysLT1 receptors, montelukast prevents vasoconstriction, proliferation and migration of smooth muscle cells, adhesion molecule expression, and leukocyte recruitment induced by CysLTs.Montelukast may improve endothelial function and reduce vascular remodeling in apneic patients.
A pharmacological blockade of CysLT pathway would be an interesting therapeutic strategy to limit the cardiovascular consequences of OSAS.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Montelukast will be crushed and coated in a capsule, Mannitol is into a capsule too.
入排标准
- 年龄范围
- 45 Years 至 75 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •With mild to moderate obstructive sleep apnea syndrome (apnea / hypopnea index> 15 and <30 events per hour)
- •Little symptomatic (Epworth sleepiness score <10)
- •Polysomnography within 3 months prior to inclusion
- •With a history of myocardial infarction or stroke
- •Affiliation to Social Security or beneficiary of such a scheme
- •Signed consent
排除标准
- •OSAS support by PPC
- •Chronic inflammatory disease
- •Asthma previously treated with Montelukast
- •Chronic infectious disease
- •Epworth sleepiness scale ≥10
- •Contraindication to Montelukast: Hypersensitivity to the active substance or to the excipients
- •Contraindications to trinitrin: hypersensitivity to nitrates, state of shock, severe hypotension, association with sildenafil, obstructive cardiomyopathy, inferior right sided myocardial infarction with right ventricular extension, acute, except in case of signs left ventricular failure, intracranial hypertension, breastfeeding
- •Treatment with phenobarbital, phenytoin, rifampicin: risk of montelukast metabolism increase and thus decrease of its effectiveness
- •Persons referred in Articles L1121-5 to L1121-8 of the CSP (pregnant woman, parturient, nursing mothers, person deprived of liberty by judicial or administrative decision, person subject to a measure of legal protection, can not be included in clinical trials)
- •Subject in exclusion period of another study
- •Subject can not be contacted in case of emergency
研究组 & 干预措施
Montelukast
Drug :Montelukast, capsule, 10mg, one per day in the evening, one hour before or 2 hours post meal, length of treatment 3 months
干预措施: Montelukast 10mg (Drug)
Montelukast
Drug :Montelukast, capsule, 10mg, one per day in the evening, one hour before or 2 hours post meal, length of treatment 3 months
干预措施: Placebo (Drug)
Placebo
Drug: Mannitol, capsule, 350mg, one per day in the evening, one hour before or 2 hours post meal, length of treatment 3 months
干预措施: Montelukast 10mg (Drug)
Placebo
Drug: Mannitol, capsule, 350mg, one per day in the evening, one hour before or 2 hours post meal, length of treatment 3 months
干预措施: Placebo (Drug)
结局指标
主要结局
Change in FMD of the brachial artery between the beginning and end of each treatment period (Montelukast and placebo), expressed as absolute value (FMD unit is %) and measured in a standardized manner.
时间窗: before and after 3 months treatment
次要结局
- Concentrations of urinary LTE4 at the beginning and end of each treatment period(before and after 3 months the two periods of treatment)
- 24h ambulatory blood pressure (systolic and diastolic) measurement(before and after 3 months of the two periods of treatment, and 15 days after the last period)
- Plasma concentration of Montelukast measured by HPLC-MS at the end of the Montelukast treatment period(at the end of Montelukast treatment period)
- Collection of adverse events(from inclusion to 15 days after the last period of treatment)
- Polysomnography at inclusion and at the end of each treatment period(inclusion and at the end of the two periods of treatment)
- Comparison of Cardiovascular Events occurence (myocardial infarction, Stroke, Cardiovascular Death) between the two periods(from inclusion to 15 days after the last period of treatment)
- Concentrations of plasma CRPus at baseline and at the beginning and end of each treatment period(before and after 3 months the two periods of treatment)