Montelukast for Patients With Obstructive Sleep Apnea Syndrome (MONTSAS)

February 15, 2021 updated by: University Hospital, Grenoble

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

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.

Study Overview

Status

Terminated

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

1

Phase

  • Phase 3

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
      • Bron, France, 69677
        • University Hospital
      • Chambéry, France, 73000
        • Métropole Savoie Hospital
      • Clermont-Ferrand, France, 63003
        • University Hospital
      • Grenoble, France, 38043
        • University Hospital
      • Grenoble, France, 38000
        • University Hospital Grenoble
      • Metz-Tessy, France, 74370
        • Annecy Genevois Hospital
      • Pierre-Bénite, France, 69495
        • University Hospital
      • Saint-Étienne, France, 42055
        • University Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

43 years to 73 years (Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Montelukast
Drug :Montelukast, capsule, 10mg, one per day in the evening, one hour before or 2 hours post meal, length of treatment 3 months
Drug: Montelukast 10mg
The capsules will be presented in box of 95 capsules packaged in unit blister
Drug: Placebo
Mannitol 350mg The capsules will be presented in box of 95 capsules packaged in unit blister
Placebo Comparator: Placebo
Drug: Mannitol, capsule, 350mg, one per day in the evening, one hour before or 2 hours post meal, length of treatment 3 months
Drug: Montelukast 10mg
The capsules will be presented in box of 95 capsules packaged in unit blister
Drug: Placebo
Mannitol 350mg The capsules will be presented in box of 95 capsules packaged in unit blister

What is the study measuring?

Primary Outcome Measures

Outcome 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.
Time Frame: before and after 3 months treatment
before and after 3 months treatment

Secondary Outcome Measures

Outcome Measure
Time Frame
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
before and after 3 months the two periods of treatment
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
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
Time Frame: inclusion and at the end of the two periods of treatment
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
Time Frame: at the end of Montelukast treatment period
at the end of Montelukast treatment period
Collection of adverse events
Time Frame: from inclusion to 15 days after the last period of treatment
from inclusion to 15 days after the last period of treatment
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
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
Time Frame: before and after 3 months the two periods of treatment
before and after 3 months the two periods of treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Hospital, Grenoble

Collaborators

Direction Générale de l'Offre de Soins
Act For Chronic Diseases

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

November 29, 2019

Primary Completion (Actual)

March 20, 2020

Study Completion (Actual)

March 20, 2020

Study Registration Dates

First Submitted

May 16, 2018

First Submitted That Met QC Criteria

June 4, 2018

First Posted (Actual)

June 6, 2018

Study Record Updates

Last Update Posted (Actual)

February 17, 2021

Last Update Submitted That Met QC Criteria

February 15, 2021

Last Verified

February 1, 2021

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 38RC17.107

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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