Sleep Apnea, Obstructive
Conditions
Keywords
Montelukast, leukotriene pathway, endothelial function, flux-mediated dilation
Brief summary
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.
Detailed description
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.
Interventions
DRUGMontelukast 10mg
The capsules will be presented in box of 95 capsules packaged in unit blister
DRUGPlacebo
Mannitol 350mg The capsules will be presented in box of 95 capsules packaged in unit blister
Sponsors
Act For Chronic Diseases
Direction Générale de l'Offre de Soins
University Hospital, Grenoble
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Montelukast will be crushed and coated in a capsule, Mannitol is into a capsule too.
Intervention model description
It's a prospective, randomized, comparative vs placebo, double blind, multicenter, national study.
Eligibility
Sex/Gender
ALL
Age
45 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* OSAS support by PPC * Cancer * 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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| 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. | before and after 3 months treatment |
Secondary
| Measure | Time frame |
|---|---|
| 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 |
| Polysomnography at inclusion and at the end of each treatment period | inclusion and at the end of the two periods of treatment |
| Plasma concentration of Montelukast measured by HPLC-MS at the end of the Montelukast treatment period | at the end of Montelukast treatment period |
| Concentrations of urinary LTE4 at the beginning and end of each treatment period | before and after 3 months 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 |
| Collection of adverse events | from inclusion to 15 days after the last period of treatment |
Countries
France
Outcome results
None listed