AsthmaE-TypeNCT01841164
A Mechanistic Study to Evaluate the Efficacy of Montelukast on Airway Function in Asthma
A study testing Montelukast and Inhaled leukotriene E4 in people with Asthma, run by Karolinska University Hospital at 1 site in Sweden.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 to 55 years
- Conditions the study is for
- Asthma
- What is being tested?
- Montelukast and Inhaled leukotriene E4
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 14 participants
- Where
- 1 siteSweden
- Study dates
- May 2012to Dec 2014
- Phase
- Interventional
- 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 18 to 55 years
- All sexes
- No healthy volunteers
- Adult
Who may be able to join
- 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
Show all 10Show fewer
- 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
- -
Who cannot join
- Any significant respiratory disease, other than asthma.
- Subjects with seasonal asthma may not be included if they are in their season.
- Use of:
- oral or inhaled glucocorticosteroid treatment for the last 4 weeks prior to inclusion or during the study
- inhaled long-acting or oral beta2-agonists, anticholinergic bronchodilators, antihistamines, theophyllines, chromones and antileukotrienes within 2 weeks of screening
- regular NSAIDs
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- drugs that inhibit the enzyme CYP3A (e.g. ritonavir, azol, antifungals, macrolides)
- beta-blocking agents
- Upper or lower respiratory tract infection within 4 weeks before inclusion
- 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
- -
Trial locations and contacts
1 site in 1 country.
Sweden1 site, 1 recruiting
- Recruiting
Karolinska University Hospital
Stockholm, SE -141 86
Ann-Sofie Lantz, RN, +46 8 58580000 ext. 6785, ann-sofie.lantz@ki.se
Barbro Dahlén, MD PhD
About this study
Official title: 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
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
Read the detailed description
Rationale: It has been proposed that there is a specific LTE4-receptor which causes infiltration of inflammatory cells and bronchoconstriction. This receptor is not blocked by the current class of clinically used antileukotriene drugs. The proposal receives circumstantial support from animal models, but has not been tested in a controlled study in subjects with asthma.
Study design: The study will have a placebo-controlled, double-blind, randomised, cross-over design. A screening period will precede the randomized phase. This will include routine haematology, blood chemistry and urinalyses, baseline measurements of exhaled nitric oxide, airway responsiveness to inhaled methacholine and, on a separate day, airway responsiveness to inhaled LTE4. Provided the subjects fulfill inclusion but not exclusion criteria, subjects will be randomized to receive medication with montelukast or matching placebo for 5 to 7 days. The intervention will be evaluated in the inhalation challenge setting using a rising dose cumulative protocol for inhaled LTE4 to induce a standardised bronchoconstriction (25% drop in lung function). The LTE4 challenge test is performed on the last treatment day, with the last dose of study medication taken in the research laboratory. Sampling of urine, blood and induced sputum will be done for measurements of lipid mediators and cellular responses.
- Conditions
- Asthma
- Being tested
- Montelukast, Placebo for montelukast, Inhaled leukotriene E4
- Keywords
- Leukotriene responsiveness, LTE4, asthma, airway hyperresponsiveness, bronchoprovocation, anti-asthmatic agents, human
- Medical subject headings
- Asthma, Respiratory Hypersensitivity
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MontelukastDrug
Also called Singulair
Placebo for montelukastDrug
Sugar pills manufactured to mimic Singulair
Inhaled leukotriene E4Other
Also called LTE4
Inhalation challenge with aerosolized GMP-grade LTE4 (Cayman Chemical Company 1180 East Ellsworth Road, Ann Arbor, Michigan 48108,USA)
| Study group | Role | What they receive |
|---|---|---|
| Montelukast | Experimental | 5 to 7 days of treatment with montelukast 10 mg 2 tablets bid. Efficacy of treatment is evaluated on airway responsiveness to inhaled leukotriene E4. Receives: Drug: Montelukast; Other: Inhaled leukotriene E4 |
| Sugar pill | Placebo comparator | Placebo for montelukast 5-7 days 2 tablets bid. Efficacy of treatment is evaluated on airway responsiveness to inhaled leukotriene E4. Receives: Drug: Placebo for montelukast; Other: Inhaled leukotriene E4 |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to three years
Secondary outcomes (1)
Airway inflammation measured as sputum eosinophils
To establish the effect of oral treatment with the highly selective CysLT1-receptor antagonist montelukast on airway inflammation, assessed as sputum cells, induced by inhaled LTE4, in subjects with intermittent asthma.
Measured: Up to three years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted26 Apr 2013 (estimated)
- Study startMay 2012
- Primary completionJun 2014 (estimated)
- Study completionDec 2014 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for AsthmaStudies of the same condition, open and under way.
- More trials run by Karolinska University HospitalThe 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 N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 14 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Karolinska University Hospital
- Sponsor type
- University, hospital or other
- Collaborators
- Karolinska Institutet
- Responsible party
- Principal investigator, Barbro Dahlen, Karolinska University Hospital
- Investigators
- Barbro Dahlen, MD PhD, Principal investigator, Karolinska Institutet and Karolinska University Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01841164
- Sponsor's protocol ID
- E-Type 4 KI_Cfa
- Acronym
- E-Type
- Status last verified
- Apr 2013
- First submitted
- 15 Apr 2013
- Last updated
- 26 Apr 2013
- Results posted
- No
- Data monitoring committee
- No
Publications
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.
PubMed 29518425
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2013. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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
- ClinicalTrials.gov ID
- NCT01841164
- Acronym / sponsor ID
- E-Type / E-Type 4 KI_Cfa
- Conditions
- Asthma
- Keywords
- Leukotriene responsiveness, LTE4, asthma, airway hyperresponsiveness, bronchoprovocation, anti-asthmatic agents, human
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 14 participants (estimated)
- Lead sponsor
- Karolinska University HospitalUniversity, hospital or other
- Collaborators
- Karolinska Institutet
- Study start
- May 2012
- Primary completion
- Jun 2014 (estimated)
- Study completion
- Dec 2014 (estimated)
- First posted
- 26 Apr 2013 (estimated)
- 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.
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
Detailed description
Rationale: It has been proposed that there is a specific LTE4-receptor which causes infiltration of inflammatory cells and bronchoconstriction. This receptor is not blocked by the current class of clinically used antileukotriene drugs. The proposal receives circumstantial support from animal models, but has not been tested in a controlled study in subjects with asthma.
Study design: The study will have a placebo-controlled, double-blind, randomised, cross-over design. A screening period will precede the randomized phase. This will include routine haematology, blood chemistry and urinalyses, baseline measurements of exhaled nitric oxide, airway responsiveness to inhaled methacholine and, on a separate day, airway responsiveness to inhaled LTE4. Provided the subjects fulfill inclusion but not exclusion criteria, subjects will be randomized to receive medication with montelukast or matching placebo for 5 to 7 days. The intervention will be evaluated in the inhalation challenge setting using a rising dose cumulative protocol for inhaled LTE4 to induce a standardised bronchoconstriction (25% drop in lung function). The LTE4 challenge test is performed on the last treatment day, with the last dose of study medication taken in the research laboratory. Sampling of urine, blood and induced sputum will be done for measurements of lipid mediators and cellular responses.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Montelukast | Experimental | Drug: Montelukast, Other: Inhaled leukotriene E45 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 comparator | Drug: Placebo for montelukast, Other: Inhaled leukotriene E4Placebo for montelukast 5-7 days 2 tablets bid. Efficacy of treatment is evaluated on airway responsiveness to inhaled leukotriene E4. |
Who may qualify
- Ages
- 18 to 55 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (10 listed)
- Be aged 18-55 years inclusive
- Have a diagnosed history of asthma as defined by at least one of the following:
- 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.
Key exclusion criteria (14 listed)
- Any significant respiratory disease, other than asthma.
- Subjects with seasonal asthma may not be included if they are in their season.
- Use of:
- Upper or lower respiratory tract infection within 4 weeks before inclusion
- 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
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 |
|---|---|---|
| MontelukastAlso: Singulair | Drug | Montelukast |
| Placebo for montelukastSugar pills manufactured to mimic Singulair | Drug | Sugar pill |
| Inhaled leukotriene E4Also: LTE4Inhalation challenge with aerosolized GMP-grade LTE4 (Cayman Chemical Company 1180 East Ellsworth Road, Ann Arbor, Michigan 48108,USA) | Other | Montelukast, Sugar pill |
Primary outcome
Bronchoconstriction measured as LTE4 PD20.
Time frame: Up to three years
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.
1 secondary outcome
Airway inflammation measured as sputum eosinophils
Time frame: Up to three years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2013.
- Derived from this study: PubMed 29518425Lazarinis 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.
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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.
Barbro Dahlen, MD PhD principal investigator
Karolinska Institutet and Karolinska University Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Montelukast and Inhaled leukotriene E4 in people with Asthma, run by Karolinska University Hospital at 1 site in Sweden.
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 10 inclusion and 14 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: status not confirmed, as of the sponsor's last update on 26 Apr 2013. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Sweden. 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.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Ann-Sofie Lantz, Registered nurse (+ 46 8 5858 0000 ext. 6785, Ann-Sofie.Lantz@ki.se), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Bronchoconstriction measured as LTE4 PD20. (time frame: Up to three years). 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 NCT01841164, which also lists 1 linked publication.
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 26 Apr 2013.