Montelukast for Childhood Asthma

(TEAM Trial)

Overseen by Donald H Arnold, MD, MPH

Age: < 18

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2

Recruiting

Sponsor: Vanderbilt University Medical Center

Must not be taking: Acid-blocking medications

Disqualifiers: Liver disease, Neuropsychiatric disorders, others

Prior Safety Data

Trial Summary

What is the purpose of this trial?

This trial is testing montelukast in children aged 4-12 with severe asthma attacks that don't respond well to standard treatments. Montelukast helps by blocking substances that cause airway inflammation, potentially improving breathing. The study aims to find the right dose that improves asthma symptoms.

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.

What data supports the effectiveness of the drug Montelukast for childhood asthma?

Research shows that Montelukast, also known as Singulair, is effective in reducing asthma symptoms in children, decreasing the need for rescue medication like albuterol, and improving lung function. It is favored for its ease of use as a once-daily oral medication, which helps with consistent use. ^{1 2 3 4 5}

Is Montelukast safe for children with asthma?

Montelukast is generally well tolerated in children with asthma, with a safety profile similar to a placebo (a harmless pill used in studies for comparison). However, in rare cases, it might be associated with Churg-Strauss syndrome, a condition that causes blood vessel inflammation. ^{5 6 7 8 9}

What makes the drug Montelukast unique for treating childhood asthma?

Montelukast is unique for treating childhood asthma because it is an oral medication that combines bronchoprotective, bronchodilating, and anti-inflammatory effects, making it a good option for children who have difficulty with inhalation therapy. It is also effective in reducing asthma symptoms and improving lung function, whether used alone or with inhaled corticosteroids. ^{1 7 9 10 11}

Research Team

Donald H Arnold, MD, MPH

Principal Investigator

Vanderbilt University School of Medicine

Eligibility Criteria

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.

Trial Timeline

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

Treatment Details

Interventions

• Albuterol (Bronchodilator)
• Corticosteroid (Corticosteroid)
• Montelukast (Leukotriene Inhibitor)

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.

Participant Groups

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 Canada for the following indications:

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+

Jeffrey R. Balser

Vanderbilt University Medical Center

Chief Executive Officer since 2009

MD and PhD from Vanderbilt University

Rick W. Wright

Vanderbilt University Medical Center

Chief Medical Officer since 2023

MD from University of Missouri-Columbia

Findings from Research

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]

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]

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]

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]

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 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]

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]

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 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.

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]

References

1. Israel pubmed.ncbi.nlm.nih.gov

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

2. United States pubmed.ncbi.nlm.nih.gov

Effect of montelukast on peripheral airflow obstruction in children with asthma. [2021]

3. Denmark 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. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Comparative study of budesonide inhalation suspension and montelukast in young children with mild persistent asthma. [2021]

5. United States pubmed.ncbi.nlm.nih.gov

Use of oral montelukast in the treatment of asthma. [2021]

6. New Zealand pubmed.ncbi.nlm.nih.gov

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

7. Canada pubmed.ncbi.nlm.nih.gov

Montelukast. No current use for asthma. [2021]

8. England pubmed.ncbi.nlm.nih.gov

Adverse events are rare after single-dose montelukast exposures in children. [2021]

9. Belgium pubmed.ncbi.nlm.nih.gov

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

10. England pubmed.ncbi.nlm.nih.gov

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

11. France pubmed.ncbi.nlm.nih.gov

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