- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00116324
Predicting the Response to Montelukast by Genetic Variation in Asthmatics
May 14, 2021 updated by: Elliot Israel, MD, Brigham and Women's Hospital
Predicting the Bronchoprotective Response to a Leukotriene Modifier by Genetic Polymorphism
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.
Study Overview
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 Type
Interventional
Enrollment
150
Phase
- Phase 3
Contacts and Locations
This section provides the contact details for those conducting the study, and information on where this study is being conducted.
Study Locations
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Massachusetts
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Boston, Massachusetts, United States, 02115
- Brigham and Women's Hospital
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Participation Criteria
Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.
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:
- 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 Plan
This section provides details of the study plan, including how the study is designed and what the study is measuring.
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Double
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
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Change in hypertonic saline PD20
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Secondary Outcome Measures
Outcome Measure |
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Improved asthma control
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Change in exhaled breath condensate inflammatory markers
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Collaborators and Investigators
This is where you will find people and organizations involved with this study.
Sponsor
Collaborators
Publications and helpful links
The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.
General 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. doi: 10.1164/ajrccm/146.1.104.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
- 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.
Study record dates
These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.
Study Major Dates
Study Start
April 1, 2003
Study Completion (Actual)
December 1, 2006
Study Registration Dates
First Submitted
June 28, 2005
First Submitted That Met QC Criteria
June 28, 2005
First Posted (Estimate)
June 29, 2005
Study Record Updates
Last Update Posted (Actual)
May 18, 2021
Last Update Submitted That Met QC Criteria
May 14, 2021
Last Verified
May 1, 2021
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
- 2002-P-001696
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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