Predicting the Response to Montelukast by Genetic Variation in Asthmatics - Full Text View

Sponsors and Collaborators:	Brigham and Women's Hospital Merck
Information provided by:	Brigham and Women's Hospital
ClinicalTrials.gov Identifier:	NCT00116324

Purpose

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.

Condition	Intervention	Phase
Asthma	Drug: Montelukast	Phase III

MedlinePlus related topics: Asthma

Drug Information available for: Sodium chloride Montelukast sodium Montelukast

U.S. FDA Resources

Study Type:	Interventional
Study Design:	Treatment, Randomized, Double-Blind, Placebo Control, Crossover Assignment, Efficacy Study
Official Title:	Predicting the Bronchoprotective Response to a Leukotriene Modifier by Genetic Polymorphism

Further study details as provided by Brigham and Women's Hospital:

Primary Outcome Measures:

Change in hypertonic saline PD20

Secondary Outcome Measures:

Improved asthma control
Change in exhaled breath condensate inflammatory markers

Estimated Enrollment:	150
Study Start Date:	April 2003
Study Completion Date:	December 2006

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.

Eligibility

Ages Eligible for Study:	18 Years to 65 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

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

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00116324

Locations

United States, Massachusetts
Brigham and Women's Hospital
Boston, Massachusetts, United States, 02115

Sponsors and Collaborators

Brigham and Women's Hospital

Merck

Investigators

Principal Investigator:

Elliot Israel, MD

Brigham and Women's Hospital

More Information

Publications:

Drazen JM, O'Brien J, Sparrow D, Weiss ST, Martins MA, Israel E, Fanta CH. Recovery of leukotriene E4 from the urine of patients with airway obstruction. Am Rev Respir Dis. 1992 Jul;146(1):104-8.

Taylor GW, Taylor I, Black P, Maltby NH, Turner N, Fuller RW, Dollery CT. Urinary leukotriene E4 after antigen challenge and in acute asthma and allergic rhinitis. Lancet. 1989 Mar 18;1(8638):584-8.

Drazen JM, Yandava CN, Dube L, Szczerback N, Hippensteel R, Pillari A, Israel E, Schork N, Silverman ES, Katz DA, Drajesk J. Pharmacogenetic association between ALOX5 promoter genotype and the response to anti-asthma treatment. Nat Genet. 1999 Jun;22(2):168-70.

In KH, Asano K, Beier D, Grobholz J, Finn PW, Silverman EK, Silverman ES, Collins T, Fischer AR, Keith TP, Serino K, Kim SW, De Sanctis GT, Yandava C, Pillari A, Rubin P, Kemp J, Israel E, Busse W, Ledford D, Murray JJ, Segal A, Tinkleman D, Drazen JM. Naturally occurring mutations in the human 5-lipoxygenase gene promoter that modify transcription factor binding and reporter gene transcription. J Clin Invest. 1997 Mar 1;99(5):1130-7.

Sanak M, Simon HU, Szczeklik A. Leukotriene C4 synthase promoter polymorphism and risk of aspirin-induced asthma. Lancet. 1997 Nov 29;350(9091):1599-600. No abstract available.

Sampson AP, Siddiqui S, Buchanan D, Howarth PH, Holgate ST, Holloway JW, Sayers I. Variant LTC(4) synthase allele modifies cysteinyl leukotriene synthesis in eosinophils and predicts clinical response to zafirlukast. Thorax. 2000 Oct;55 Suppl 2:S28-31. No abstract available.

Anderson PJ, Garshick E, Blanchard JD, Feldman HA, Brain JD. Intersubject variability in particle deposition does not explain variability in responsiveness to methacholine. Am Rev Respir Dis. 1991 Sep;144(3 Pt 1):649-54.

Study ID Numbers:	2002-P-001696
Study First Received:	June 28, 2005
Last Updated:	April 2, 2007
ClinicalTrials.gov Identifier:	NCT00116324
Health Authority:	United States: Institutional Review Board

Keywords provided by Brigham and Women's Hospital:

Asthma
Leukotriene receptor antagonist
Hypertonic saline challenge

Study placed in the following topic categories:

Montelukast
Hypersensitivity
Lung Diseases, Obstructive
Respiratory Tract Diseases
Lung Diseases

Hypersensitivity, Immediate
Asthma
Leukotriene Antagonists
Respiratory Hypersensitivity

Additional relevant MeSH terms:

Respiratory System Agents
Immune System Diseases
Bronchial Diseases
Therapeutic Uses
Hormone Antagonists

Physiological Effects of Drugs
Hormones, Hormone Substitutes, and Hormone Antagonists
Anti-Asthmatic Agents
Pharmacologic Actions

ClinicalTrials.gov processed this record on January 14, 2009