Montelukast for Childhood Asthma

(TEAM Trial)

Overseen By Donald H Arnold, MD, MPH

Age: < 18

Sex: Any

Trial Phase: Phase 2

Sponsor: Vanderbilt University Medical Center

Must not be taking: Acid-blocking medications

Disqualifiers: Liver disease, Neuropsychiatric disorders, others

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: 1

Duration: 24 hours

90 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment approach for children with asthma who experience moderate to severe attacks. Researchers aim to determine if adding higher doses of montelukast, a medication that reduces airway inflammation, to standard asthma treatments can more effectively improve symptoms. The study compares this enhanced treatment to standard care alone to identify the best dose for future studies. Children aged 4-12 with diagnosed asthma, who have significant flare-ups even after initial treatment, might be suitable for this trial. As a Phase 2 trial, this research focuses on measuring the treatment's effectiveness in an initial, smaller group, offering participants a chance to contribute to important advancements in asthma care.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but it does mention that patients already taking daily montelukast can still participate.

Is there any evidence suggesting that this treatment is likely to be safe for humans?

Research shows that montelukast is generally safe for children with asthma. In studies, children aged 6 to 14 did not experience major issues while taking it for eight weeks. However, montelukast can sometimes cause mental health side effects, though these are uncommon. The FDA has approved montelukast for treating asthma and allergies, indicating it meets their safety standards. For those considering joining a trial, it is reassuring that many children have used montelukast safely before. It is important to monitor for any unusual feelings or symptoms. ^{1 2 3 4 5}

Why do researchers think this study treatment might be promising?

Montelukast is unique because it offers a different approach to treating childhood asthma by targeting leukotrienes, which are chemicals involved in inflammation and bronchoconstriction. Most treatments, like albuterol and corticosteroids, focus on relaxing airway muscles or reducing inflammation through other pathways. Montelukast's mechanism may complement these standard treatments, potentially providing better control of asthma symptoms. Researchers are excited about montelukast's potential to enhance the effectiveness of existing therapies and improve outcomes for children with asthma.

What evidence suggests that high-dose oral montelukast might be an effective treatment for childhood asthma?

Research shows that montelukast helps reduce asthma attacks in children. Studies found that montelukast can lower the number of asthma episodes from about 2.34 to 1.60 per year compared to a placebo. In this trial, one group of participants will receive high-dose oral montelukast in addition to standard treatment, while another group will receive an identical placebo alongside standard treatment. Montelukast is widely accepted as a first treatment option for children with mild asthma. It can be effective on its own or when used with inhaled corticosteroids, helping to control asthma in kids. These findings support using montelukast to manage asthma symptoms effectively. ^{1 6 7 8 9}

Who Is on the Research Team?

Donald H Arnold, MD, MPH

Principal Investigator

Vanderbilt University School of Medicine

Are You a Good Fit for This Trial?

This trial is for children aged 4-12 with doctor-diagnosed asthma, who come to Vanderbilt Children's Hospital with a moderate or severe asthma attack after albuterol treatment. They must not have liver disease, allergy to montelukast, significant breast development in girls, acid reflux on medication, certain mental health conditions except ADHD, or high risk of suicide.

Inclusion Criteria

My child, aged 4-12, has been diagnosed with asthma by a doctor.

My child's asthma got worse even after using albuterol.

The parent agrees to phone and/or mail follow-up at 2-3 weeks for completion of SCARED and side-effect questionnaires.

Exclusion Criteria

You have indicated having thoughts of suicide on the Columbia Suicide Severity Rating Scale.

I have liver disease.

I have a history of anxiety, depression, or another mental health condition, but not ADHD.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-3 weeks

1 visit (in-person)

Treatment

Participants receive escalating doses of oral montelukast or placebo, with plasma levels monitored to determine dose efficacy

24 hours

Multiple visits (in-person) for blood sampling and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment, including follow-up for anxiety and side-effect questionnaires

2-3 weeks

Phone and/or mail follow-up

What Are the Treatments Tested in This Trial?

Interventions

• Albuterol
• Corticosteroid
• Montelukast

Trial Overview The study tests if high-dose oral montelukast added to standard care (albuterol and corticosteroids) can improve symptoms more than standard care alone in kids with serious asthma attacks. It's a blinded trial where doses are adjusted based on drug levels in the blood and response.

How Is the Trial Designed?

Group I: High-dose oral montelukast plus standard treatment Experimental Treatment 3 Interventions

Escalating dose-levels of oral montelukast between 2 mg/kg and 3 mg/kg determined by pharmacokinetic-guided dose modeling, added to standard, guideline-based treatment (systemic corticosteroid, inhaled albuterol, and possible treatment adjuncts such as IV magnesium, determined by evidence-based asthma clinical practice guideline).

Group II: Identical placebo plus standard treatment Placebo Group 2 Interventions

Guideline-based treatment (systemic corticosteroid, inhaled albuterol, and possible treatment adjuncts such as IV magnesium, determined by evidence-based asthma clinical practice guideline).

Albuterol is already approved in United States, European Union, Canada for the following indications:

Approved in United States as Albuterol for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Exercise-induced bronchospasm

Approved in European Union as Salbutamol for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Exercise-induced bronchospasm

Approved in Canada as Salbutamol for:

• Asthma
• Chronic obstructive pulmonary disease (COPD)
• Exercise-induced bronchospasm

Who Is Running the Clinical Trial?

Vanderbilt University Medical Center

Lead Sponsor

Trials

922

Recruited

939,000+

Published Research Related to This Trial

A study analyzing 17,069 montelukast exposures in children aged 5-17 years found that single doses, even up to 445 mg, are rarely associated with adverse events, indicating a strong safety profile for this medication.

The most common adverse event reported was abdominal pain, which was dose-related, but no serious or life-threatening events occurred, suggesting that montelukast is safe for use in children when taken as directed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Adverse events are rare after single-dose montelukast exposures in children. Arnold, DH., Bowman, N., Reiss, TF., et al.[2021]

Montelukast is an effective treatment for asthma, providing bronchoprotective, bronchodilating, and anti-inflammatory effects, and is recommended for patients whose asthma is not adequately controlled by inhaled corticosteroids.

The drug is well tolerated, does not require serum monitoring, and can be used alongside inhaled corticosteroids to improve symptoms and lung function in both adults and children.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Pharma-clinics. Medication of the month. Montelukast (Singulair)]. Louis, R.[2021]

Montelukast is an effective leukotriene modifier for treating asthma in both adults and children, providing improved relief from asthma symptoms.

It has a rapid onset of action, a safety profile similar to that of a placebo, and is taken once daily, which promotes better adherence to treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Use of oral montelukast in the treatment of asthma. Noonan, GP., Williams, B., Angner, R., et al.[2021]

Montelukast treatment in grass-allergic patients significantly reduced eosinophil survival compared to placebo, indicating its effectiveness in managing asthma symptoms by affecting immune cell behavior.

The study found that montelukast suppressed the production of GM-CSF, a key cytokine that enhances eosinophil survival, suggesting that it works by inhibiting this cytokine's production from peripheral blood mononuclear cells.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Treatment of asthmatic patients with a cysteinyl leukotriene receptor-1 antagonist montelukast (Singulair), decreases the eosinophil survival-enhancing activity produced by peripheral blood mononuclear leukocytes in vitro. Becler, K., Håkansson, L., Rak, S.[2021]

Montelukast is effective in improving clinical scores and respiratory function in patients with chronic asthma and in preventing effort-induced asthma, based on several placebo-controlled trials.

There is no significant difference in side effects between montelukast and placebo, although rare cases of Churg and Strauss syndrome may be associated with its use.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Montelukast: new preparation. No current use in asthma. [2007]

Montelukast significantly improved lung function in children aged 6 to 14 years with asthma, showing an 8.23% increase in forced expiratory volume (FEV1) compared to 3.58% in the placebo group during an 8-week trial with 336 participants.

The treatment also led to a notable reduction in asthma symptoms and exacerbations, with no significant difference in adverse events between montelukast and placebo, indicating its safety for use in this age group.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical evidence with montelukast in the management of chronic childhood asthma. Becker, A.[2021]

In a study involving 506 children aged 2 to 18 with mild to moderate persistent asthma, montelukast (Singulair) significantly improved asthma symptoms and treatment compliance over a 6-week period.

The treatment was well-received by both pediatricians and parents, indicating high satisfaction with montelukast as an effective monotherapy for managing childhood asthma.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Real-life effectiveness of Singulair (montelukast) in 506 children with mild to moderate asthma. Amirav, I.[2021]

Montelukast sodium is an effective oral medication for treating allergic asthma and allergic rhinitis in both adults and children, with approval for use in children as young as 6 months for allergic rhinitis.

Recently, montelukast was approved in the US for preventing exercise-induced bronchoconstriction in patients aged 15 and older, highlighting its expanding role in managing respiratory conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Update on montelukast and its role in the treatment of asthma, allergic rhinitis and exercise-induced bronchoconstriction. Storms, W.[2021]

Montelukast is effective in improving clinical scores and respiratory function in patients with chronic asthma and in preventing effort-induced asthma, based on several placebo-controlled trials.

While montelukast has not been directly compared to all standard treatments for asthma, it may be superior to salmeterol for effort-induced asthma, and it generally has a similar side effect profile to placebo, though rare cases of Churg-Strauss syndrome have been reported.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Montelukast. No current use for asthma. [2021]

In a study of 21 children with mild-to-moderate asthma, montelukast treatment for 8 weeks significantly reduced measures of airway obstruction, including lower residual volume and airway resistance, compared to placebo.

Montelukast also led to decreased levels of serum eosinophil cationic protein, indicating reduced airway inflammation, although it did not significantly improve forced expiratory volume or overall asthma symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effect of montelukast on peripheral airflow obstruction in children with asthma. Spahn, JD., Covar, RA., Jain, N., et al.[2021]

In a study of children aged 2 to 8 with mild asthma, budesonide inhalation suspension showed a longer time to first additional asthma medication and lower exacerbation rates compared to montelukast over 52 weeks, suggesting better long-term efficacy.

While both treatments were effective, budesonide resulted in fewer children needing oral corticosteroids (25.5% vs 32.0% for montelukast), indicating a potential safety advantage in managing asthma symptoms.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Comparative study of budesonide inhalation suspension and montelukast in young children with mild persistent asthma. Szefler, SJ., Baker, JW., Uryniak, T., et al.[2021]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4079631/

Clinical effectiveness and safety of montelukast in asthma ... There is well-accepted evidence that oral montelukast is an effective initial preventer therapy for children with mild asthma. 57,58 In addition, it seems to ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC2528689/

Is montelukast effective and well tolerated in the ... Asthma exacerbations were reduced from an average of 2.34 episodes per year in the placebo group to 1.60 episodes per year in the treatment group (P<0.001). In ...

3. clinicaltrials.gov clinicaltrials.gov/study/NCT01266772

NCT01266772 | Effect of Montelukast in Asthma in Children The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure.

4. aacijournal.biomedcentral.com aacijournal.biomedcentral.com/articles/10.1186/1710-1492-10-21

Effectiveness of montelukast administered as monotherapy or ... Montelukast as monotherapy or in combination with ICS represents an effective treatment strategy for achieving asthma control in pediatric patients.

5. clinicaltrials.gov clinicaltrials.gov/study/NCT00755794

Study Details | NCT00755794 | The Singulair® add-on ... The purpose of this study is to evaluate the effectiveness of adding Montelukast Sodium (singulair®) 10 mg per day to inhaled corticosteroids in adult subjects ...

6. fda.gov fda.gov/drugs/drug-safety-and-availability/fda-requires-boxed-warning-about-serious-mental-health-side-effects-asthma-and-allergy-drug

Boxed Warning about mental health side effects for Singulair Montelukast is FDA-approved for asthma and allergies. It is a prescription medicine approved to prevent asthma attacks and for long-term ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11946223/

The Impact of Montelukast Duration ... - PubMed Central - NIH Previous studies have demonstrated that montelukast can reduce the risk of asthma exacerbations in children with mild intermittent asthma and ...

8. scientificamerican.com scientificamerican.com/article/asthma-drug-still-being-prescribed-to-kids-despite-potential-mental-health-risks/

Asthma Drug Still Being Prescribed to Kids Despite ... The allergy and asthma drug montelukast, also known as Singulair, can cause psychiatric side effects—and researchers aren't sure why.

9. jamanetwork.com jamanetwork.com/journals/jama/fullarticle/187439

Montelukast for Chronic Asthma in 6- to 14-Year-Old Children Overall, montelukast was generally well tolerated over the 8-week treatment period in 6- to 14-year-old patients. Future studies will be needed ...