Moderate to Persistent Asthma in the Obese Subject

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

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.

Study Overview

• Status: Terminated
• Conditions: Asthma
• Intervention / Treatment: Drug: Montelukast; Other: Sugar pill

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and will be placed on inhaled corticosteroids at moderate doses and leukotriene receptor antagonists will be withdrawn (LTRA wash-out).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

• Study Type: Interventional
• Enrollment (Actual): 38
• Phase: Phase 4

Contacts and Locations

Study Locations

• United States
  • North Carolina
    • Durham, North Carolina, United States, 27704
      • Duke Asthma Allergy and Airway Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Diagnostic
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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

Collaborators and Investigators

• Sponsor: Duke University

Study record dates

Study Major Dates

• Study Start: January 1, 2010
• Primary Completion (Actual): November 1, 2013
• Study Completion (Actual): November 1, 2013

Study Registration Dates

• First Submitted: October 19, 2009
• First Submitted That Met QC Criteria: November 19, 2009
• First Posted (Estimate): November 20, 2009

Study Record Updates

• Last Update Posted (Estimate): November 17, 2014
• Last Update Submitted That Met QC Criteria: November 7, 2014
• Last Verified: December 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Respiratory Tract Diseases; Immune System Diseases; Lung Diseases; Hypersensitivity, Immediate; Bronchial Diseases; Lung Diseases, Obstructive; Respiratory Hypersensitivity; Hypersensitivity; Asthma; 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: Pro00018748