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Montelukast for Patients With Obstructive Sleep Apnea Syndrome (MONTSAS)

Primary Purpose

Sleep Apnea, Obstructive

Status
Terminated
Phase
Phase 3
Locations
France
Study Type
Interventional
Intervention
Montelukast 10mg
Placebo
Sponsored by
University Hospital, Grenoble
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Sleep Apnea, Obstructive focused on measuring Montelukast, leukotriene pathway, endothelial function, flux-mediated dilation

Eligibility Criteria

45 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept 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

Sites / Locations

  • University Hospital
  • Métropole Savoie Hospital
  • University Hospital
  • University Hospital Grenoble
  • University Hospital
  • Annecy Genevois Hospital
  • University Hospital
  • University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Montelukast

Placebo

Arm Description

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

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

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

Concentrations of urinary LTE4 at the beginning and end of each treatment period
24h ambulatory blood pressure (systolic and diastolic) measurement
Polysomnography at inclusion and at the end of each treatment period
Plasma concentration of Montelukast measured by HPLC-MS at the end of the Montelukast treatment period
Collection of adverse events
Comparison of Cardiovascular Events occurence (myocardial infarction, Stroke, Cardiovascular Death) between the two periods
Concentrations of plasma CRPus at baseline and at the beginning and end of each treatment period

Full Information

First Posted
May 16, 2018
Last Updated
February 15, 2021
Sponsor
University Hospital, Grenoble
Collaborators
Act For Chronic Diseases, Direction Générale de l'Offre de Soins
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1. Study Identification

Unique Protocol Identification Number
NCT03545997
Brief Title
Montelukast for Patients With Obstructive Sleep Apnea Syndrome
Acronym
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
Study Type
Interventional

2. Study Status

Record Verification Date
February 2021
Overall Recruitment Status
Terminated
Why Stopped
lack of recruitment
Study Start Date
November 29, 2019 (Actual)
Primary Completion Date
March 20, 2020 (Actual)
Study Completion Date
March 20, 2020 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Hospital, Grenoble
Collaborators
Act For Chronic Diseases, Direction Générale de l'Offre de Soins

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Sleep Apnea, Obstructive
Keywords
Montelukast, leukotriene pathway, endothelial function, flux-mediated dilation

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 3
Interventional Study Model
Crossover Assignment
Model Description
It's a prospective, randomized, comparative vs placebo, double blind, multicenter, national study.
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Masking Description
Montelukast will be crushed and coated in a capsule, Mannitol is into a capsule too.
Allocation
Randomized
Enrollment
1 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Montelukast
Arm Type
Experimental
Arm Description
Drug :Montelukast, capsule, 10mg, one per day in the evening, one hour before or 2 hours post meal, length of treatment 3 months
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
Drug: Mannitol, capsule, 350mg, one per day in the evening, one hour before or 2 hours post meal, length of treatment 3 months
Intervention Type
Drug
Intervention Name(s)
Montelukast 10mg
Intervention Description
The capsules will be presented in box of 95 capsules packaged in unit blister
Intervention Type
Drug
Intervention Name(s)
Placebo
Intervention Description
Mannitol 350mg The capsules will be presented in box of 95 capsules packaged in unit blister
Primary Outcome Measure Information:
Title
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.
Time Frame
before and after 3 months treatment
Secondary Outcome Measure Information:
Title
Concentrations of urinary LTE4 at the beginning and end of each treatment period
Time Frame
before and after 3 months the two periods of treatment
Title
24h ambulatory blood pressure (systolic and diastolic) measurement
Time Frame
before and after 3 months of the two periods of treatment, and 15 days after the last period
Title
Polysomnography at inclusion and at the end of each treatment period
Time Frame
inclusion and at the end of the two periods of treatment
Title
Plasma concentration of Montelukast measured by HPLC-MS at the end of the Montelukast treatment period
Time Frame
at the end of Montelukast treatment period
Title
Collection of adverse events
Time Frame
from inclusion to 15 days after the last period of treatment
Title
Comparison of Cardiovascular Events occurence (myocardial infarction, Stroke, Cardiovascular Death) between the two periods
Time Frame
from inclusion to 15 days after the last period of treatment
Title
Concentrations of plasma CRPus at baseline and at the beginning and end of each treatment period
Time Frame
before and after 3 months the two periods of treatment

10. Eligibility

Sex
All
Minimum Age & Unit of Time
45 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Facility Information:
Facility Name
University Hospital
City
Bron
ZIP/Postal Code
69677
Country
France
Facility Name
Métropole Savoie Hospital
City
Chambéry
ZIP/Postal Code
73000
Country
France
Facility Name
University Hospital
City
Clermont-Ferrand
ZIP/Postal Code
63003
Country
France
Facility Name
University Hospital Grenoble
City
Grenoble
ZIP/Postal Code
38000
Country
France
Facility Name
University Hospital
City
Grenoble
ZIP/Postal Code
38043
Country
France
Facility Name
Annecy Genevois Hospital
City
Metz-Tessy
ZIP/Postal Code
74370
Country
France
Facility Name
University Hospital
City
Pierre-Bénite
ZIP/Postal Code
69495
Country
France
Facility Name
University Hospital
City
Saint-Étienne
ZIP/Postal Code
42055
Country
France

12. IPD Sharing Statement

Plan to Share IPD
Undecided
Citations:
PubMed Identifier
22244598
Citation
Ingelsson E, Yin L, Back 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.
Results Reference
background
PubMed Identifier
22869829
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.
Results Reference
background
PubMed Identifier
23204025
Citation
Cereza G, Garcia Dolade 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. No abstract available.
Results Reference
background
PubMed Identifier
23375423
Citation
Marchand MS, Jonville-Bera AP, Autret-Leca E; Association francaise des centres regionaux de pharmacovigilance. [Psychiatric disorders associated with montelukast: data from the National Pharmacovigilance Database]. Arch Pediatr. 2013 Mar;20(3):269-73. doi: 10.1016/j.arcped.2012.12.006. Epub 2013 Feb 1. French.
Results Reference
background

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Montelukast for Patients With Obstructive Sleep Apnea Syndrome

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