A Mechanistic Study to Evaluate the Efficacy of Montelukast on Airway Function in Asthma
E-Type
A Study of the Effects of the Selective CysLT1 Antagonist Montelukast on Bronchoconstriction and Airway Inflammation Induced by Inhalation of Leukotriene E4 in Subjects With Asthma
1 other identifier
interventional
14
1 country
1
Brief Summary
The trial is an investigator-driven research study in subjects with intermittent asthma, the aim of which is to explore the likelihood of a functionally important separate leukotriene E4 (LTE4) receptor in airways and/or inflammatory cells in human subjects with asthma. Mostly on the basis of experiments in mice models, the prevailing view suggests that the present class of anti-leukotriene drugs are insufficient because they do not block the pro-inflammatory and bronchoconstrictive effects of LTE4. It is established by us and other groups that LTE4 is the most stable and long-lived leukotriene. The study will establish the effect of oral treatment with the highly selective CysLT1-receptor antagonist, montelukast, on bronchial responsiveness to inhaled LTE4 in subjects with intermittent asthma
Trial Health
Trial Health Score
Automated assessment based on enrollment pace, timeline, and geographic reach
participants targeted
Target at below P25 for not_applicable asthma
Started May 2012
Typical duration for not_applicable asthma
1 active site
Health score is calculated from publicly available data and should be used for screening purposes only.
Trial Relationships
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Study Timeline
Key milestones and dates
Study Start
First participant enrolled
May 1, 2012
CompletedFirst Submitted
Initial submission to the registry
April 15, 2013
CompletedFirst Posted
Study publicly available on registry
April 26, 2013
CompletedPrimary Completion
Last participant's last visit for primary outcome
June 1, 2014
CompletedStudy Completion
Last participant's last visit for all outcomes
December 1, 2014
CompletedApril 26, 2013
April 1, 2013
2.1 years
April 15, 2013
April 23, 2013
Conditions
Keywords
Outcome Measures
Primary Outcomes (1)
Bronchoconstriction measured as LTE4 PD20.
To establish the effect of oral treatment with the highly selective CysLT1-receptor antagonist montelukast on bronchial responsiveness to inhaled LTE4 in subjects with intermittent asthma.
Up to three years
Secondary Outcomes (1)
Airway inflammation measured as sputum eosinophils
Up to three years
Study Arms (2)
Montelukast
EXPERIMENTAL5 to 7 days of treatment with montelukast 10 mg 2 tablets bid. Efficacy of treatment is evaluated on airway responsiveness to inhaled leukotriene E4.
Sugar pill
PLACEBO COMPARATORPlacebo for montelukast 5-7 days 2 tablets bid. Efficacy of treatment is evaluated on airway responsiveness to inhaled leukotriene E4.
Interventions
Inhalation challenge with aerosolized GMP-grade LTE4 (Cayman Chemical Company 1180 East Ellsworth Road, Ann Arbor, Michigan 48108,USA)
Eligibility Criteria
You may qualify if:
- Be aged 18-55 years inclusive
- Have a diagnosed history of asthma as defined by at least one of the following:
- response to standard asthma treatment
- episodic wheezing
- change in lung function over short periods of time
- Be a non-smoker for the last two years and a total of smoking less than 5 pack-years
- Display a positive methacholine challenge test as evidenced by a PD20 (provocative dose causing 20% fall in forced expiratory volume in one second) ≤ 3621 µg cumulated dose within 8 weeks prior to screening or at the screening visit.
- Have stable intermittent asthma, only using bronchodilator therapy as needed for the last 4 weeks.
- Produce FEV1 (forced expiratory volume in one second) ≥ 70 % of predicted
You may not qualify if:
- Any significant respiratory disease, other than asthma.
- Subjects with seasonal asthma may not be included if they are in their season.
- Use of:
- inhaled long-acting or oral beta2-agonists, anticholinergic bronchodilators, antihistamines, theophyllines, chromones and antileukotrienes within 2 weeks of screening
- regular NSAIDs
- drugs that inhibit the enzyme CYP3A (e.g. ritonavir, azol, antifungals, macrolides)
- beta-blocking agents
- Evidence (from medical history or physical examination) of any disease that in the investigators mind would affect the results of the study, in particular liver disease and/or signs of liver function impairment
- Participating in another study in the four weeks prior to screening
- Females who are pregnant, intend to be or who are lactating
- Subjects with history of aspirin-sensitive respiratory disease
Contact the study team to confirm eligibility.
Sponsors & Collaborators
- Karolinska University Hospitallead
- Karolinska Institutetcollaborator
Study Sites (1)
Karolinska University Hospital
Stockholm, SE -141 86, Sweden
Related Publications (1)
Lazarinis N, Bood J, Gomez C, Kolmert J, Lantz AS, Gyllfors P, Davis A, Wheelock CE, Dahlen SE, Dahlen B. Leukotriene E4 induces airflow obstruction and mast cell activation through the cysteinyl leukotriene type 1 receptor. J Allergy Clin Immunol. 2018 Oct;142(4):1080-1089. doi: 10.1016/j.jaci.2018.02.024. Epub 2018 Mar 5.
PMID: 29518425DERIVED
MeSH Terms
Conditions
Interventions
Condition Hierarchy (Ancestors)
Intervention Hierarchy (Ancestors)
Study Officials
- PRINCIPAL INVESTIGATOR
Barbro Dahlen, MD PhD
Karolinska Institutet and Karolinska University Hospital
Central Study Contacts
Study Design
- Study Type
- interventional
- Phase
- not applicable
- Allocation
- RANDOMIZED
- Masking
- QUADRUPLE
- Who Masked
- PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
- Purpose
- BASIC SCIENCE
- Intervention Model
- CROSSOVER
- Sponsor Type
- OTHER
- Responsible Party
- PRINCIPAL INVESTIGATOR
- PI Title
- Senior Consultant, MD PhD
Study Record Dates
First Submitted
April 15, 2013
First Posted
April 26, 2013
Study Start
May 1, 2012
Primary Completion
June 1, 2014
Study Completion
December 1, 2014
Last Updated
April 26, 2013
Record last verified: 2013-04