Clinical trial NCT03039101: Leukotriene Antagonism in Recruitment of CD49d Expressing Neutrophils in Atopic Subjects
Official title: Double Blind Study of Leukotriene Antagonism in the Nasal Recruitment of CD49d Expressing Neutrophils in Atopic Subjects
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Nasal Allergy
Keywords: allergen
neutrophils
allergy
Lead sponsor: Nationwide Children's Hospital
Sponsor class: OTHER
Collaborators: name: National Heart, Lung, and Blood Institute (NHLBI)
First posted: 2017-02-01
Enrollment: 25
Sex: ALL
Minimum age (years): 21
Maximum age (years): 65
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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: 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).

Eligibility criteria: 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

Primary outcomes:
measure: Change in frequency in CD49d+ neutrophils in the nasal lavage post-allergen challenge on placebo versus Montelukast.
timeFrame: 1 month
Secondary outcomes:
measure: Change in clinical response following nasal allergen challenge after one week of treatment with Montelukast.
timeFrame: 1 month
Other outcomes:
measure: Induction of expression of immunoglobulin E (IgE) receptor on dendritic cells following exposure with CD49d+ cells from peripheral blood samples.
timeFrame: 1 month
Locations:
city: Columbus
country: United States
facility: Nationwide Children's Hospital
state: Ohio
Study officials:
affiliation: Nationwide Children's Hospital
name: Mitchell H Grayson, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Sigua JA, Buelow B, Cheung DS, Buell E, Hunter D, Klancnik M, Grayson MH. CD49d-expressing neutrophils differentiate atopic from nonatopic individuals. J Allergy Clin Immunol. 2014 Mar;133(3):901-4.e5. doi: 10.1016/j.jaci.2013.09.035. Epub 2013 Dec 18. No abstract available.
citation: Cheung DS, Ehlenbach SJ, Kitchens RT, Riley DA, Thomas LL, Holtzman MJ, Grayson MH. Cutting edge: CD49d+ neutrophils induce FcepsilonRI expression on lung dendritic cells in a mouse model of postviral asthma. J Immunol. 2010 Nov 1;185(9):4983-7. doi: 10.4049/jimmunol.1002456. Epub 2010 Sep 27.
citation: Khan SH, Grayson MH. Cross-linking IgE augments human conventional dendritic cell production of CC chemokine ligand 28. J Allergy Clin Immunol. 2010 Jan;125(1):265-7. doi: 10.1016/j.jaci.2009.09.038. Epub 2009 Dec 4. No abstract available.
citation: Subrata LS, Bizzintino J, Mamessier E, Bosco A, McKenna KL, Wikstrom ME, Goldblatt J, Sly PD, Hales BJ, Thomas WR, Laing IA, LeSouef PN, Holt PG. Interactions between innate antiviral and atopic immunoinflammatory pathways precipitate and sustain asthma exacerbations in children. J Immunol. 2009 Aug 15;183(4):2793-800. doi: 10.4049/jimmunol.0900695. Epub 2009 Jul 20.
citation: Cheung DS, Ehlenbach SJ, Kitchens T, Riley DA, Grayson MH. Development of atopy by severe paramyxoviral infection in a mouse model. Ann Allergy Asthma Immunol. 2010 Dec;105(6):437-443.e1. doi: 10.1016/j.anai.2010.09.010.
citation: Grayson MH, Cheung D, Rohlfing MM, Kitchens R, Spiegel DE, Tucker J, Battaile JT, Alevy Y, Yan L, Agapov E, Kim EY, Holtzman MJ. Induction of high-affinity IgE receptor on lung dendritic cells during viral infection leads to mucous cell metaplasia. J Exp Med. 2007 Oct 29;204(11):2759-69. doi: 10.1084/jem.20070360. Epub 2007 Oct 22.
citation: Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B, Bjorksten B. Asthma and immunoglobulin E antibodies after respiratory syncytial virus bronchiolitis: a prospective cohort study with matched controls. Pediatrics. 1995 Apr;95(4):500-5.
citation: Sammon LM, Hussain SA, Smith M, Rohlfing M, Santoro JL, Grayson MH. Effect of cysteinyl leukotriene receptor 1 blockade on aeroallergen-induced nasal recruitment of CD49d expressing neutrophils. Ann Allergy Asthma Immunol. 2019 Nov;123(5):508-511.e1. doi: 10.1016/j.anai.2019.08.019. Epub 2019 Sep 3. No abstract available.