Leukotriene Antagonism in Recruitment of CD49d Expressing Neutrophils in Atopic Subjects

Nasal Allergy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03039101
• Other study ID #: IRB16-00842
• Secondary ID: R01HL087778
• Status: Completed
• Phase: N/A
• Start date: September 6, 2017
• Est. completion date: July 16, 2018

Study information

• Verified date: October 2019
• Source: Nationwide Children's Hospital
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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).

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).

Recruitment information / eligibility

• Status: Completed
• Enrollment: 25
• Est. completion date: July 16, 2018
• Est. primary completion date: July 16, 2018
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 65 Years

Eligibility

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

Related Conditions & MeSH terms

• Hypersensitivity
• Nasal Allergy

Intervention

Procedure:
• Nasal lavage
determine frequency of CD49d expressing neutrophils in the nasal lavage by flow cytometry
• Nasal allergen challenge
A small amount of allergen extract will be applied to one naris.
• Epicutaneous skin testing
Skin testing (prick) to determine allergies.
• Peripheral blood
Peripheral blood draw

Drug:
• Montelukast 10Mg Tablet
one pill orally, daily, for 1 week
• Placebo Oral Tablet
one pill orally, daily, for 1 week

Locations

Country	Name	City	State
United States	Nationwide Children's Hospital	Columbus	Ohio

Sponsors (2)

Lead Sponsor	Collaborator
Mitchell Grayson	National Heart, Lung, and Blood Institute (NHLBI)

Country where clinical trial is conducted

United States, 

References & Publications (8)

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. — View 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. — View 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. Epub 2007 Oct 22. — View 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. — View Citation

Sammon LM, Hussain SA, Smith M, Rohlfing M, Santoro JL, Grayson MH. Effect of cysLTR1 blockade on aeroallergen-induced nasal recruitment of CD49d expressing neutrophils. Ann Allergy Asthma Immunol. 2019 Sep 3. pii: S1081-1206(19)30608-8. doi: 10.1016/j.an — View 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. — View Citation

Sigurs N, Bjarnason R, Sigurbergsson F, Kjellman B, Björkstén 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. — View Citation

Subrata LS, Bizzintino J, Mamessier E, Bosco A, McKenna KL, Wikström ME, Goldblatt J, Sly PD, Hales BJ, Thomas WR, Laing IA, LeSouëf 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Induction of expression of immunoglobulin E (IgE) receptor on dendritic cells following exposure with CD49d+ cells from peripheral blood samples.	An additional outcome will be whether CD49d+ neutrophils from peripheral blood can induce increased expression of the IgE receptor (FceRI) on dendritic cells (also isolated from the peripheral blood).	1 month
Primary	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	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