Sleep Apnea, ObstructivePhase 3MONTSASNCT03545997
Montelukast for Patients With Obstructive Sleep Apnea Syndrome
A Phase 3 study testing Montelukast 10mg in people with Sleep Apnea, Obstructive, run by University Hospital, Grenoble at 8 sites in France.
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. Read more about this study
- Who is it for?
- Ages 45 to 75 years
- Conditions the study is for
- Sleep Apnea, Obstructive
- What is being tested?
- Montelukast 10mg
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 1 participants
- Where
- 8 sitesFrance
- Study dates
- 29 Nov 2019to 20 Mar 2020
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- OSAS support by PPC
- Cancer
- Chronic inflammatory disease
- Asthma previously treated with Montelukast
- Chronic infectious disease
- Epworth sleepiness scale ≥10
Show all 12Show fewer
- 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 locations and contacts
8 sites in 1 country.
8 sites in 1 country
France8 sites
University Hospital
Bron, 69677
Métropole Savoie Hospital
Chambéry, 73000
University Hospital
Clermont-Ferrand, 63003
University Hospital Grenoble
Grenoble, 38000
University Hospital
Grenoble, 38043
Annecy Genevois Hospital
Metz-Tessy, 74370
University Hospital
Pierre-Bénite, 69495
University Hospital
Saint-Etienne, 42055
About this study
Official title: 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.
Read the 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.
- Conditions
- Sleep Apnea, Obstructive
- Being tested
- Montelukast 10mg, Placebo
- Keywords
- Montelukast, leukotriene pathway, endothelial function, flux-mediated dilation
- Medical subject headings
- Sleep Apnea, Obstructive
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Montelukast 10mgDrug
The capsules will be presented in box of 95 capsules packaged in unit blister
PlaceboDrug
Mannitol 350mg The capsules will be presented in box of 95 capsules packaged in unit blister
| Study group | Role | What they receive |
|---|---|---|
| Montelukast | Experimental | Drug :Montelukast, capsule, 10mg, one per day in the evening, one hour before or 2 hours post meal, length of treatment 3 months Receives: Drug: Montelukast 10mg; Drug: Placebo |
| Placebo | Placebo comparator | Drug: Mannitol, capsule, 350mg, one per day in the evening, one hour before or 2 hours post meal, length of treatment 3 months Receives: Drug: Montelukast 10mg; Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: before and after 3 months treatment
Secondary outcomes (7)
Concentrations of urinary LTE4 at the beginning and end of each treatment period
Measured: before and after 3 months the two periods of treatment
24h ambulatory blood pressure (systolic and diastolic) measurement
Measured: 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
Measured: 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
Measured: at the end of Montelukast treatment period
Collection of adverse events
Measured: 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
Measured: 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
Measured: before and after 3 months the two periods of treatment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jun 2018
- Study start29 Nov 2019
- Primary completion20 Mar 2020
- Study completion20 Mar 2020
Why it stopped: lack of recruitment
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (4)Papers the sponsor has linked to this study.
- Other trials for Sleep Apnea, ObstructiveStudies of the same condition, open and under way.
- More trials run by University Hospital, GrenobleThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- It's a prospective, randomized, comparative vs placebo, double blind, multicenter, national study.
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 1 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Grenoble
- Sponsor type
- University, hospital or other
- Collaborators
- Act For Chronic Diseases, Direction Générale de l'Offre de Soins
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03545997
- Sponsor's protocol ID
- 38RC17.107
- Acronym
- MONTSAS
- Status last verified
- Feb 2021
- First submitted
- 16 May 2018
- Last updated
- 17 Feb 2021
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
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.
PubMed 22244598Goldbart 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.
PubMed 22869829Cereza 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.
PubMed 23204025Marchand 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.
PubMed 23375423
Study at a glance
From the registry record, last updated by the sponsor on 17 Feb 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Impact of Blocked Cysteinyl Leukotriene Pathway on Endothelial Function in Patients With Obstructive Sleep Apnea Syndrome: Multicenter Randomized Placebo Controlled Crossover Trial
- ClinicalTrials.gov ID
- NCT03545997
- Acronym / sponsor ID
- MONTSAS / 38RC17.107
- Conditions
- Sleep Apnea, Obstructive
- Keywords
- Montelukast, leukotriene pathway, endothelial function, flux-mediated dilation
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: lack of recruitment
- Enrolment
- 1 participants (actual)
- Lead sponsor
- University Hospital, GrenobleUniversity, hospital or other
- Collaborators
- Act For Chronic Diseases, Direction Générale de l'Offre de Soins
- Study start
- 29 Nov 2019 (actual)
- Primary completion
- 20 Mar 2020 (actual)
- Study completion
- 20 Mar 2020 (actual)
- First posted
- 6 Jun 2018 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- It's a prospective, randomized, comparative vs placebo, double blind, multicenter, national study.
| Arm | Type | Receives |
|---|---|---|
| Montelukast | Experimental | Drug: Montelukast 10mg, Drug: PlaceboDrug :Montelukast, capsule, 10mg, one per day in the evening, one hour before or 2 hours post meal, length of treatment 3 months |
| Placebo | Placebo comparator | Drug: Montelukast 10mg, Drug: PlaceboDrug: Mannitol, capsule, 350mg, one per day in the evening, one hour before or 2 hours post meal, length of treatment 3 months |
Who may qualify
- Ages
- 45 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- 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
Key exclusion criteria (12 listed)
- OSAS support by PPC
- Cancer
- Chronic inflammatory disease
- Asthma previously treated with Montelukast
- Chronic infectious disease
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Montelukast 10mgThe capsules will be presented in box of 95 capsules packaged in unit blister | Drug | Montelukast, Placebo |
| PlaceboMannitol 350mg The capsules will be presented in box of 95 capsules packaged in unit blister | Drug | Montelukast, Placebo |
Primary outcome
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
7 secondary outcomes
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
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
Polysomnography at inclusion and at the end of each treatment period
Time frame: 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
Collection of adverse events
Time frame: 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
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
Results and safety
The study was stopped early (reason given: lack of recruitment). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Feb 2021.
- Background: PubMed 22244598Ingelsson 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.
- Background: PubMed 22869829Goldbart 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.
- Background: PubMed 23204025Cereza 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.
- Background: PubMed 23375423Marchand 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.
- Individual participant dataSharing planned: Undecided
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
8 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Montelukast 10mg in people with Sleep Apnea, Obstructive, run by University Hospital, Grenoble at 8 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: stopped early, as of the sponsor's last update on 17 Feb 2021. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 8 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study was stopped early (reason given: lack of recruitment). Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT03545997, which also lists 4 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 17 Feb 2021.