Moderate to Persistent Asthma in the Obese Subject

Phase 4

Terminated

Brief Summary: 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: 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and will be placed on inhaled corticosteroids at moderate doses and leukotriene receptor antagonists will be withdrawn (LTRA wash-out).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.

Recruitment & Eligibility

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

Arm && Interventions

Group	Intervention	Description
Sugar Pill	Sugar pill	High dose of inhaled steroid administered with sugar pill
leukotriene receptor antagonist (LTRA) montelukast	Montelukast	Montelukast (LTRA) administered with moderate dose of inhaled steroid

Primary Outcome Measures

Name	Time	Method
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

Name	Time	Method
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	Baseline/randomization to week 16	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.
Sputum Cell Counts and Differentials	Baseline/randomization to week 16