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

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.

Study Overview

• Status: Completed
• Conditions: Inflammation; Obesity; Asthma
• Intervention / Treatment: Drug: Montelukast; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 26
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • New York
    • Great Neck, New York, United States, 11023
      • North Shore-Long Island Jewish Health System, Division of Allergy/Immunology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 7 years to 17 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Obese atopic asthmatics, montelukast; 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; Age-dependent dose, nightly, 24 weeks; Other Names: Singulair
Placebo Comparator: Lean atopic asthmatics, placebo; 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; Age-dependent dose, nightly, 24 weeks
Active Comparator: Lean atopic asthmatics, montelukast; 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; Age-dependent dose, nightly, 24 weeks; Other Names: Singulair
Placebo Comparator: Obese atopic asthmatics, Placebo; 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; Age-dependent dose, nightly, 24 weeks

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Northwell Health
• Collaborators: Merck Sharp & Dohme LLC; Thrasher Research Fund; New York State Department of Health
• Investigators: Principal Investigator: Sherry Farzan, MD, Northwell Health

Publications and helpful links

General Publications

• Farzan S, Khan S, Elera C, Tsang J, Akerman M, DeVoti J. Effectiveness of montelukast in overweight and obese atopic asthmatics. Ann Allergy Asthma Immunol. 2017 Aug;119(2):189-190. doi: 10.1016/j.anai.2017.05.024. Epub 2017 Jun 28. No abstract available.

Study record dates

Study Major Dates

• Study Start: April 1, 2011
• Primary Completion (Actual): September 1, 2014
• Study Completion (Actual): September 1, 2014

Study Registration Dates

• First Submitted: March 23, 2011
• First Submitted That Met QC Criteria: April 5, 2011
• First Posted (Estimate): April 6, 2011

Study Record Updates

• Last Update Posted (Estimate): April 7, 2016
• Last Update Submitted That Met QC Criteria: March 9, 2016
• Last Verified: March 1, 2016

More Information

Terms related to this study

• Keywords: Inflammation; Obesity; Asthma; Pediatric; Montelukast; Leukotriene
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Body Weight; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Inflammation; Asthma; Overweight; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Montelukast
• Other Study ID Numbers: 10-029B

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No