Predicting the Response to Montelukast by Genetic Variation in Asthmatics

Mass General Brigham

Status and phase

Completed

Phase 3

Conditions

Asthma

Treatments

Drug: Montelukast

Study type

Interventional

Funder types

Other

Industry

Identifiers

NCT00116324

2002-P-001696

Details and patient eligibility

About

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.

Full 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.

Sex

All

Ages

18 to 65 years old

Volunteers

No Healthy Volunteers

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