The Effect of Montelukast on Asthma Control in Overweight/Obese Atopic Asthmatics

Study Overview
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Brief Summary
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Background: In recent years, the prevalence of both asthma and obesity has risen dramatically among children and adolescents in the United States. Given the concurrent rise in the two epidemics, there may be an underlying link. Obesity contributes to asthma severity and control, and may play a role in its underlying cause. Obesity is associated with a state of heightened inflammation that may lead to an increase asthma symptoms and severity. Obese adult patients treated with montelukast, an anti-inflammatory agent, seemed to have better asthma control than those treated with other standard asthma medications. The use of montelukast in obese children and adolescents has not been specifically studied. Hypotheses and Specific Aims: The use of montelukast will improve asthma symptoms and objective markers of asthma to a greater degree in obese, as opposed to non-obese children and adolescents. The investigators would like to determine if the use of montelukast will improve objective asthma scores, pulmonary function, markers of inflammation and medication use to a greater degree in obese as opposed to non-obese children/adolescents. Potential Impact: Given the growing epidemic of obesity-associated asthma in the U.S., a tailored approach focused on obese asthmatic children may help reduce the burden of this disease, health care costs and potential long-term complications as these children enter adulthood. Furthermore, this study may help clarify the underlying mechanisms that link asthma and obesity. Although this proposal is focused on one medication, it provides an example of how certain medications may have differential efficacy in the obese asthmatic.

Official Title
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The Effect of Montelukast on Asthma Control in Overweight/Obese Atopic Asthmatics

Conditions
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Asthma, Obesity, Inflammation

Intervention / Treatment
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* Drug: Montelukast
* Drug: Placebo
* Drug: Montelukast
* Drug: Placebo


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: mild to moderate persistent asthma based on 2007 NIH Asthma Guidelines age 7-17 years old Exclusion Criteria: present smoking or smoking history other significant pulmonary or cardiac condition recent (within the past three months) use of montelukast on allergen immunotherapy on omalizumab pregnancy

Ages Eligible for Study
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Minimum Age: 7 Years
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Obese atopic asthmatics, montelukast<br>Obese/overweight (BMI 85%ile or above for children and > 25 for adults) mild to moderate persistent asthmatics age 7 and above, with environmental allergies who were on daily inhaled corticosteroid treatment and not on montelukast, were randomized to receive montelukast in a double blinded fashion. | Drug: Montelukast<br>* Age-dependent dose, nightly, 24 weeks<br>* Other names: Singulair;|
| Placebo Comparator: Lean atopic asthmatics, placebo<br>Normal weight (BMI less than 85%ile or above for children and < 25 for adults) mild to moderate persistent asthmatics age 7 and above, with environmental allergies who were on daily inhaled corticosteroid treatment and not on montelukast, were randomized to receive placebo in a double blinded fashion. | Drug: Placebo<br>* Age-dependent dose, nightly, 24 weeks<br>|
| Active Comparator: Lean atopic asthmatics, montelukast<br>Normal weight (BMI less than 85%ile or above for children and < 25 for adults) mild to moderate persistent asthmatics age 7 and above, with environmental allergies who were on daily inhaled corticosteroid treatment and not on montelukast, were randomized to receive montelukast in a double blinded fashion. | Drug: Montelukast<br>* Age-dependent dose, nightly, 24 weeks<br>* Other names: Singulair;|
| Placebo Comparator: Obese atopic asthmatics, Placebo<br>Obese/overweight (BMI 85%ile or above for children and > 25 for adults) mild to moderate persistent asthmatics age 7 and above, with environmental allergies who were on daily inhaled corticosteroid treatment and not on montelukast, were randomized to receive placebo in a double blinded fashion. | Drug: Placebo<br>* Age-dependent dose, nightly, 24 weeks<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Asthma Control Test (ACT) Scores | The ACT is a validated questionaire-based tool designed to assess asthma control. Scale range for 7-11 year olds is 0-27 and for 12 years and older 5-25, with lower scores indicating poorer asthma control for all ages. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis. | 24 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Spirometric Measures | Breathing maneuvers which help to measure obstruction of airways. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis. | 24 weeks | 
| Serum Leptin Levels | Leptin levels, measured through blood, mediate appetite and are elaborated by adipose tissue. Levels correlate positively with body fat percentage. In addition, leptin plays a role in producing an inflammatory state. Adiponectin, which is also secreted by adipose tissue, regulates metabolism, however its levels are inversely correlated with body fat percentage. | 24 weeks | 
| Urinary Leukotriene E4 (LTE4) Levels | LTE4 levels, measured in the urine, reflect the degree of inflammation in the asthmatic airway. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis. | 24 weeks | 
| Exhaled Nitric Oxide Measurement | A non-invasive measure of eosinophilic airway inflammation. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis. | 24 weeks | 
| Beclomethasone Equivalents | The total daily dose of inhaled corticosteroids in beclomethasone equivalents. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis. | 24 weeks | 
| Urinary Creatinine (Cr) Levels | Creatinine, measured in the urine, reflects how well the kidneys are working, and provide a standard to which one can compare other metabolites in the urine. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis. | 24 weeks | 
| Urinary Creatinine (Cr) Levels/Leukotriene E4 (LTE4) Ratio | The ratio of urinary LTE4 to Cr provides a standardization of the LTE4 level based on the patients weight and muscle mass, therefore normalizing it across the different subjects. We did not perform percent change from baseline since in a randomized clinical trial, where the groups are comparable at baseline, we can use only the post-treatment (week 24) data in the analysis. | 24 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Asthma, Obesity, Pediatric, Inflammation, Leukotriene, Montelukast