Predicting the Response to Montelukast by Genetic Variation in Asthmatics

Phase 3

Completed

• Conditions: Asthma

• Registration Number: NCT00116324
• Lead Sponsor: Brigham and Women's Hospital

Brief Summary

The purpose of this study is to examine a specific variation in the genetic code for an enzyme (LTC4 synthase) which plays an important role in the airway inflammation associated with asthma. We hypothesize that asthmatic patients with this variant gene will have a better response to montelukast than patients with the wild type gene, as measured by the ability of montelukast to protect against a hypertonic saline challenge.

Detailed Description

Multiple genetic polymorphisms in the leukotriene pathway have been described but their clinical relevance is unclear. A single nucleotide polymorphism in the LTC4 synthase promoter region has been associated with increased LTC4 synthase mRNA and a trend toward improved bronchodilatory response to leukotriene modifiers in severe asthmatics. This study will examine mild to moderate asthmatics with the variant gene and evaluate the bronchoprotective response of montelukast in a double-blind, placebo-controlled cross-over fashion.

Study Timeline

• Study Start: 2003-04
• Study First Submitted: 2005-06-28
• Study First Submitted QC: 2005-06-28
• Study First Posted: 2005-06-29
• Study Completion: 2006-12
• Status Verified: 2021-05
• Last Update Submitted: 2021-05-14
• Last Update Posted: 2021-05-18

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 150

Inclusion Criteria

• Male and female subjects, age 18-55
• Clinical history consistent with asthma
• Mild to moderate asthma as determined by pulmonary function tests--60% or higher of predicted FEV1 for age, sex and race.
• Response to hypertonic saline, which will be the main outcome variable measured.

Exclusion Criteria

• Smokers (total lifetime smoking history>10 pack-years, any in the past year)
• Pregnant woman-if of childbearing age, not using an acceptable form of birth control.
• Use of a leukotriene modifier within the past month
• Use of inhaled or oral steroids within the past month.
• Emergency room visit for asthma exacerbation within the past 6 weeks.
• Intubation for asthma exacerbation in the past 10 years.
• Adverse reaction to inhaled beta-agonists in the past.
• No recent (past 48 hours) use of anticholinergics, theophylline, antihistamines, pseudoephedrine.
• Patients will also be asked not to use any short acting beta-agonists for 6 hours and long-acting beta-agonists for 48 hours before their initial visit (when pulmonary function evaluation will be performed).
• Lung disease other than asthma
• Significant medical illness other than asthma

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Change in hypertonic saline PD20

Secondary Outcome Measures

Name	Time	Method
Improved asthma control
Change in exhaled breath condensate inflammatory markers

Trial Locations

Locations (1)

Brigham and Women's Hospital; 🇺🇸 Boston, Massachusetts, United States