Montelukast for Patients With Obstructive Sleep Apnea Syndrome (MONTSAS)

Grenoble Alpes University Hospital Center (CHU)

Status and phase: Terminated; Phase 3

Conditions: Sleep Apnea, Obstructive

Treatments: Drug: Placebo; Drug: Montelukast 10mg

Study type: Interventional

Funder types: Other

Identifiers

NCT03545997

38RC17.107

Details and patient eligibility

About

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.

Full 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.

Enrollment: 1 patient

Sex: All

Ages: 45 to 75 years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Crossover Assignment

Masking: Quadruple Blind

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1 participants in 2 patient groups, including a placebo group

Montelukast

Experimental group

Description:

Drug :Montelukast, capsule, 10mg, one per day in the evening, one hour before or 2 hours post meal, length of treatment 3 months

Treatment:

Drug: Placebo

Drug: Montelukast 10mg

Placebo

Placebo Comparator group

Description:

Drug: Mannitol, capsule, 350mg, one per day in the evening, one hour before or 2 hours post meal, length of treatment 3 months

Treatment:

Drug: Placebo

Drug: Montelukast 10mg