Predicting the Response to Montelukast by Genetic Variation in Asthmatics

NCT00116324 | Completed Phase 3

• 1 other identifier: 2002-P-001696
• Study Type: interventional
• Target: 150
• Locations: 1 country
• Sites: 1

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.

Conditions

Asthma

Keywords

Asthma; Leukotriene receptor antagonist; Hypertonic saline challenge

Outcome Measures

Primary Outcomes (1)

• Change in hypertonic saline PD20

Secondary Outcomes (2)

• Improved asthma control

• Change in exhaled breath condensate inflammatory markers

Interventions

Montelukast DRUG

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Brigham and Women's Hospital: lead
• Merck Sharp & Dohme LLC: collaborator

Study Sites (1)

Brigham and Women's Hospital

Boston, Massachusetts, 02115, United States

Location

Related Publications (8)

• 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. doi: 10.1164/ajrccm/146.1.104.

  PMID: 1320817 BACKGROUND

• 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. doi: 10.1016/s0140-6736(89)91611-5.

  PMID: 2564113 BACKGROUND

• 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. doi: 10.1038/9680.

  PMID: 10369259 BACKGROUND

• 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. doi: 10.1172/JCI119241.

  PMID: 9062372 BACKGROUND

• 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. doi: 10.1016/s0140-6736(05)64015-9. No abstract available.

  PMID: 9393345 BACKGROUND

• 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(Suppl 2):S28-31. doi: 10.1136/thorax.55.suppl_2.s28. No abstract available.

  PMID: 10992553 BACKGROUND

• 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. doi: 10.1164/ajrccm/144.3_Pt_1.649.

  PMID: 1892306 BACKGROUND

• Kazani S, Sadeh J, Bunga S, Wechsler ME, Israel E. Cysteinyl leukotriene antagonism inhibits bronchoconstriction in response to hypertonic saline inhalation in asthma. Respir Med. 2011 May;105(5):667-73. doi: 10.1016/j.rmed.2010.11.025. Epub 2010 Dec 18.

  PMID: 21169002 DERIVED

MeSH Terms

Conditions

Asthma

Interventions

montelukast

Condition Hierarchy (Ancestors)

Bronchial Diseases; Respiratory Tract Diseases; Lung Diseases, Obstructive; Lung Diseases; Respiratory Hypersensitivity; Hypersensitivity, Immediate; Hypersensitivity; Immune System Diseases

Study Officials

• Elliot Israel, MD

  Brigham and Women's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Physician

Study Record Dates

• First Submitted: June 28, 2005
• First Posted: June 29, 2005
• Study Start: April 1, 2003
• Study Completion: December 1, 2006
• Last Updated: May 18, 2021

Record last verified: 2021-05

Locations

US (1)