Montelukast for Patients With Obstructive Sleep Apnea Syndrome

Sleep Apnea, Obstructive Clinical Trial

— MONTSAS  

Official title:

Impact of Blocked Cysteinyl Leukotriene Pathway on Endothelial Function in Patients With Obstructive Sleep Apnea Syndrome: Multicenter Randomized Placebo Controlled Crossover Trial

Clinical Trial Details — Status: Terminated

Administrative data

• NCT number: NCT03545997
• Other study ID #: 38RC17.107
• Status: Terminated
• Phase: Phase 3
• Start date: November 29, 2019
• Est. completion date: March 20, 2020

Study information

• Verified date: February 2021
• Source: University Hospital, Grenoble
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Terminated
• Enrollment: 1
• Est. completion date: March 20, 2020
• Est. primary completion date: March 20, 2020
• Accepts healthy volunteers: No
• Gender: All
• Age group: 45 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Apnea
• Sleep Apnea Syndromes
• Sleep Apnea, Obstructive

Intervention

Drug:
• Montelukast 10mg
The capsules will be presented in box of 95 capsules packaged in unit blister
• Placebo
Mannitol 350mg The capsules will be presented in box of 95 capsules packaged in unit blister

Locations

Country	Name	City	State
France	University Hospital	Bron
France	Métropole Savoie Hospital	Chambéry
France	University Hospital	Clermont-Ferrand
France	University Hospital	Grenoble
France	University Hospital Grenoble	Grenoble
France	Annecy Genevois Hospital	Metz-Tessy
France	University Hospital	Pierre-Bénite
France	University Hospital	Saint-Étienne

Sponsors (3)

Lead Sponsor	Collaborator
University Hospital, Grenoble	Act For Chronic Diseases, Direction Générale de l'Offre de Soins

Country where clinical trial is conducted

France, 

References & Publications (4)

Cereza G, Garcia Doladé N, Laporte JR. Nightmares induced by montelukast in children and adults. Eur Respir J. 2012 Dec;40(6):1574-5. doi: 10.1183/09031936.00092812. — View Citation

Goldbart AD, Greenberg-Dotan S, Tal A. Montelukast for children with obstructive sleep apnea: a double-blind, placebo-controlled study. Pediatrics. 2012 Sep;130(3):e575-80. doi: 10.1542/peds.2012-0310. Epub 2012 Aug 6. — View Citation

Ingelsson E, Yin L, Bäck M. Nationwide cohort study of the leukotriene receptor antagonist montelukast and incident or recurrent cardiovascular disease. J Allergy Clin Immunol. 2012 Mar;129(3):702-707.e2. doi: 10.1016/j.jaci.2011.11.052. Epub 2012 Jan 12. — View Citation

Marchand M-S, Jonville-Béra A-P, Autret-Leca E. [Psychiatric disorders associated with montelukast: data from the National Pharmacovigilance Database]. Arch pe´diatrie organe Off la Socie´te Fr pe´diatrie [Internet]. 2013 [cited 2016 Jun 14];20:269-73. Available from: http://www.ncbi.nlm.nih.gov/pubmed/23375423

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Concentrations of urinary LTE4 at the beginning and end of each treatment period		before and after 3 months the two periods of treatment
Secondary	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
Secondary	Polysomnography at inclusion and at the end of each treatment period		inclusion and at the end of the two periods of treatment
Secondary	Plasma concentration of Montelukast measured by HPLC-MS at the end of the Montelukast treatment period		at the end of Montelukast treatment period
Secondary	Collection of adverse events		from inclusion to 15 days after the last period of treatment
Secondary	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
Secondary	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