Moderate to Persistent Asthma in the Obese Subject

Study Overview
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Brief Summary
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Obesity is associated with increased airway inflammation and asthma severity that results in suboptimal control of asthma despite therapy with high dose inhaled corticosteroids (ICS). The investigators suggested that the addition of Singular (montelukast)[LTRA] to moderate doses of inhaled corticosteroids will improve asthma control. This cross over study will be treat subjects with moderate dose ICS/LTRA for 12 weeks and high dose ICS with placebo for 12 weeks.

Detailed Description
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Subjects will enter the 2-week run-in period after meeting eligibility criteria at the screening visit (visit 1). During run-in subjects will have all usual asthma medications discontinued and will be placed on inhaled corticosteroids at moderate doses and leukotriene receptor antagonists will be withdrawn (LTRA wash-out). Subjects will be monitored to rule out any acute infection or symptoms consistent with an exacerbation. The run-in period will be used to assess subject compliance and understanding of study related procedures. Following the run-in, to be eligible for the randomization subjects must have an ACQ score >1.25 on the Juniper Asthma Control Questionnaire.

Official Title
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A Randomized, Double-Blind, Placebo-Controlled, Cross-over Study to Evaluate the Effect of the Leukotriene Antagonist (Singulair©) Plus Moderate Dose Beclomethasone Compared to High Dose Beclomethasone in Obese Subjects With Moderate Persistent Asthma

Conditions
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Asthma

Intervention / Treatment
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* Drug: Montelukast
* Other: Sugar pill


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: moderate persistent asthma as defined daily symptoms, nocturnal awakenings >1 time/week but not daily, daily short-acting beta agonist usage pre-bronchodilator Force expiratory volume (FEV1)>55% but <90%. Subjects must be on controller therapy for asthma with ICS for at least one month prior to enrollment. methacholine testing that causes a drop in the FEV1 of 20% (8mg/ml off ICS or 16mg/ml) on ICS within 6 months prior to entry physician diagnosis of asthma for at least one year prior to study enrollment. Obesity defined as BMI greater than 30. subjects must have an Asthma Control Questionnaire (ACQ) score >1.25 on the Juniper Asthma Control Questionnaire (indicating poor asthma control), require daily medications for asthma and be compliant with study related medications. Exclusion Criteria: Subjects must not have been intubated in the last 5 years or unstable asthma symptoms resulting in significant loss or work or school upper or lower respiratory tract infection within 1 month of the study use of antibiotics within 4 weeks of the study use of oral glucocorticoids within 4 weeks use of theophylline smoking history greater than 10 pack years or any cigarette use within the past two years significant non-asthma pulmonary disease or other medical problems Subjects planning to undergo gastric bypass surgery within 4 months of the enrollment date will be excluded since weight loss is a potential confounder of asthma control Pregnant women will also be excluded

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 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: Diagnostic
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: leukotriene receptor antagonist (LTRA) montelukast<br>Montelukast (LTRA) administered with moderate dose of inhaled steroid | Drug: Montelukast<br>* 10 mg Q day<br>|
| Placebo Comparator: Sugar Pill<br>High dose of inhaled steroid administered with sugar pill | Other: Sugar pill<br>* Sugar pill that looks like Montelukast that will be given Q day<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Determine the Effect of Montelukast / Moderate Dose ICS Versus High Dose ICS on Asthma Control as Measured by the Asthma Control Questionnaire. |  | Baseline/randomization to week 16 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum Adiponectin, Leptin, Tumor Necrosis Alpha (TNF-α) and Interleukin 6 (IL6) Levels |  | Baseline/randomization to week 16 | 
| Post Bronchodilator Forced Expiratory Volume in 1 Second (FEV1) |  | Baseline/randomization to week 16 | 
| Change in Trends in Asthma Control Questionnaire (ACQ ACTQ) Scores Over Duration of the Study |  | Baseline/randomization to week 16 | 
| Asthma Exacerbation | Asthma exacerbation is defined as the development of an increase in asthma symptoms which results in an increase in the use of asthma medications (typically inhaled corticosteroids and/or parenteral corticosteroids) or the addition of another new asthma medication or antibiotics. | Baseline/randomization to week 16 | 
| Sputum Cell Counts and Differentials |  | Baseline/randomization to week 16 |