Montelukast for Patients With Obstructive Sleep Apnea Syndrome

NCT03545997 | Terminated Phase 3 DMC

• 1 other identifier: 38RC17.107
• Study Type: interventional
• Target: 1
• Locations: 1 country
• Sites: 8

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.

Conditions

Sleep Apnea, Obstructive

Keywords

Montelukast; leukotriene pathway; endothelial function; flux-mediated dilation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (7)

• Concentrations of urinary LTE4 at the beginning and end of each treatment period

  before and after 3 months the two periods of treatment

• 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

• Polysomnography at inclusion and at the end of each treatment period

  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

  at the end of Montelukast treatment period

• Collection of adverse events

  from inclusion to 15 days after the last period of treatment

Study Arms (2)

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

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

Drug: Montelukast 10mg; Drug: Placebo

Interventions

Montelukast 10mg DRUG

The capsules will be presented in box of 95 capsules packaged in unit blister

Montelukast; Placebo

Placebo DRUG

Mannitol 350mg The capsules will be presented in box of 95 capsules packaged in unit blister

Montelukast; Placebo

Eligibility Criteria

• Age: 45 Years - 75 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• With mild to moderate obstructive sleep apnea syndrome (apnea / hypopnea index\> 15 and \<30 events per hour)
• Little symptomatic (Epworth sleepiness score \<10)
• With a history of myocardial infarction or stroke
• Affiliation to Social Security or beneficiary of such a scheme
• Signed consent

You may not qualify if:

• 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 can not be contacted in case of emergency

Sponsors & Collaborators

• University Hospital, Grenoble: lead
• Act For Chronic Diseases: collaborator
• Direction Générale de l'Offre de Soins: collaborator

Study Sites (8)

University Hospital

Bron, 69677, France

Location

Métropole Savoie Hospital

Chambéry, 73000, France

Location

University Hospital

Clermont-Ferrand, 63003, France

Location

University Hospital Grenoble

Grenoble, 38000, France

Location

University Hospital

Grenoble, 38043, France

Location

Annecy Genevois Hospital

Metz-Tessy, 74370, France

Location

University Hospital

Pierre-Bénite, 69495, France

Location

University Hospital

Saint-Etienne, 42055, France

Location

Related Publications (4)

• 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.

  PMID: 22244598 BACKGROUND

• 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.

  PMID: 22869829 BACKGROUND

• 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.

  PMID: 23204025 BACKGROUND

• 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.

  PMID: 23375423 BACKGROUND

MeSH Terms

Conditions

Sleep Apnea, Obstructive

Interventions

montelukast

Condition Hierarchy (Ancestors)

Sleep Apnea Syndromes; Apnea; Respiration Disorders; Respiratory Tract Diseases; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Nervous System Diseases

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: Montelukast will be crushed and coated in a capsule, Mannitol is into a capsule too.
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: It's a prospective, randomized, comparative vs placebo, double blind, multicenter, national study.

Study Record Dates

• First Submitted: May 16, 2018
• First Posted: June 6, 2018
• Study Start: November 29, 2019
• Primary Completion: March 20, 2020
• Study Completion: March 20, 2020
• Last Updated: February 17, 2021

Record last verified: 2021-02

Locations

FR (8)