Leukotriene Antagonism in Recruitment of CD49d Expressing Neutrophils in Atopic Subjects

Study Overview
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Brief Summary
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The purpose of this study is to see if the recruitment of a certain cell type (the alpha 4 integrin (CD49d) expressing neutrophil) during a nasal allergen challenge can be inhibited by pretreatment with an FDA approved leukotriene antagonist (montelukast).

Detailed Description
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Subjects will be consented, undergo skin testing, medical history questionnaires, and randomized to either placebo or montelukast (10 mg). In one week, subjects return, undergo a blood draw, medical history questionnaires, nasal lavage, and nasal allergen challenge (followed by lavage in 6 hours). Subjects will then cross-over to the other study drug. One week later subjects will undergo a blood draw, medical history questionnaires, lavage, allergen challenge, and repeat lavage (after 6 hours).

Official Title
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Double Blind Study of Leukotriene Antagonism in the Nasal Recruitment of CD49d Expressing Neutrophils in Atopic Subjects

Conditions
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Nasal Allergy

Intervention / Treatment
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* Procedure: Nasal lavage
* Procedure: Nasal allergen challenge
* Procedure: Epicutaneous skin testing
* Procedure: Peripheral blood
* Drug: Montelukast 10Mg Tablet
* Drug: Placebo Oral Tablet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 21 - 65 years of age, inclusive A personal history of allergic rhinitis (hayfever) (by self-report) At least one positive skin test to cat, dust mite mix, Timothy grass, Bermuda grass, Bluegrass, or Ragweed Ability to provide informed consent Willingness to undergo epicutaneous skin testing Willingness to undergo nasal lavages and nasal allergen challenges Willingness to undergo 2 peripheral blood draws (10 cc each) Exclusion Criteria: Use of systemic antihistamine in the past 5 days Use of intranasal corticosteroids or intranasal antihistamines currently or in the past 2 weeks Use of Montelukast currently or in the past week Hypersensitivity or allergy to Montelukast Inability to perform/undergo any study procedures Pregnancy (by subject report) or breastfeeding Confirmed or suspected immunodeficiency Persistent asthma, atopic dermatitis, or any other co-morbid disease except for allergic rhinitis Any symptoms of asthma in the past 2 weeks (shortness of breath, wheezing, and/or use of albuterol) Fever (temperature over 99F) currently or in the past 2 weeks Current or previous use of a biologic or investigational agent in the past 6 months Current or past suicidal thoughts/attempts

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Montelukast<br>Subjects take 1 montelukast 10mg tablet orally, daily and effect on nasal allergen challenge (based on results of epicutaneous skin testing) induced recruitment of cd49d neutrophils in the peripheral blood and nasal lavage determined at 1 week | Procedure: Nasal lavage<br>* determine frequency of CD49d expressing neutrophils in the nasal lavage by flow cytometry<br>Procedure: Nasal allergen challenge<br>* A small amount of allergen extract will be applied to one naris.<br>Procedure: Epicutaneous skin testing<br>* Skin testing (prick) to determine allergies.<br>Procedure: Peripheral blood<br>* Peripheral blood draw<br>Drug: Montelukast 10Mg Tablet<br>* one pill orally, daily, for 1 week<br>* Other names: montelukast;|
| Placebo Comparator: Placebo<br>Subjects take 1 placebo oral pill, daily and effect on nasal allergen challenge (based on results of epicutaneous skin testing) induced recruitment of cd49d neutrophils in the peripheral blood and nasal lavage determined at 1 week. | Procedure: Nasal lavage<br>* determine frequency of CD49d expressing neutrophils in the nasal lavage by flow cytometry<br>Procedure: Nasal allergen challenge<br>* A small amount of allergen extract will be applied to one naris.<br>Procedure: Peripheral blood<br>* Peripheral blood draw<br>Drug: Placebo Oral Tablet<br>* one pill orally, daily, for 1 week<br>* Other names: placebo;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in frequency in CD49d+ neutrophils in the nasal lavage post-allergen challenge on placebo versus Montelukast. | The primary outcome will be the change in frequency (as assessed by flow cytometry) in CD49d+ neutrophils in the nasal lavage post-allergen challenge on placebo versus Montelukast. | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in clinical response following nasal allergen challenge after one week of treatment with Montelukast. | Secondary outcomes will be whether treatment with Montelukast for one week changes the clinical response to nasal allergen challenge (i.e., sneezing, itching, etc.) as documented in the validated Sino Nasal Outcome Test (SNOT)-20 questionnaire. | 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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allergen, neutrophils, allergy