Leukotriene Antagonism in Recruitment of CD49d Expressing Neutrophils in Atopic Subjects

NCT03039101 | Completed

• 2 other identifiers: IRB16-00842R01HL087778
• Study Type: interventional
• Target: 25
• Locations: 1 country
• Sites: 1

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).

Conditions

Nasal Allergy

Keywords

allergen; neutrophils; allergy

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (1)

• Change in clinical response following nasal allergen challenge after one week of treatment with Montelukast.

  1 month

Other Outcomes (1)

• Induction of expression of immunoglobulin E (IgE) receptor on dendritic cells following exposure with CD49d+ cells from peripheral blood samples.

  1 month

Study Arms (2)

Montelukast

EXPERIMENTAL

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; Procedure: Nasal allergen challenge; Procedure: Epicutaneous skin testing; Procedure: Peripheral blood; Drug: Montelukast 10Mg Tablet

Placebo

PLACEBO COMPARATOR

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; Procedure: Nasal allergen challenge; Procedure: Peripheral blood; Drug: Placebo Oral Tablet

Interventions

Nasal lavage PROCEDURE

determine frequency of CD49d expressing neutrophils in the nasal lavage by flow cytometry

Montelukast; Placebo

Nasal allergen challenge PROCEDURE

A small amount of allergen extract will be applied to one naris.

Montelukast; Placebo

Epicutaneous skin testing PROCEDURE

Skin testing (prick) to determine allergies.

Montelukast

Peripheral blood PROCEDURE

Peripheral blood draw

Montelukast; Placebo

Montelukast 10Mg Tablet DRUG

one pill orally, daily, for 1 week

Also known as: montelukast

Montelukast

Placebo Oral Tablet DRUG

one pill orally, daily, for 1 week

Also known as: placebo

Placebo

Eligibility Criteria

• Age: 21 Years - 65 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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)

You may not qualify if:

• 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

Sponsors & Collaborators

• Mitchell Grayson: lead
• National Heart, Lung, and Blood Institute (NHLBI): collaborator

Study Sites (1)

Nationwide Children's Hospital

Columbus, Ohio, 43205, United States

Location

Related Publications (8)

• 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.

  PMID: 24360325 BACKGROUND

• 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.

  PMID: 20876348 BACKGROUND

• 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.

  PMID: 19962743 BACKGROUND

• 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.

  PMID: 19620293 BACKGROUND

• 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.

  PMID: 21130381 BACKGROUND

• 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.

  PMID: 17954569 BACKGROUND

• 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.

  PMID: 7700748 BACKGROUND

• 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.

  PMID: 31491537 RESULT

MeSH Terms

Conditions

Hypersensitivity

Interventions

Nasal Lavage; montelukast

Condition Hierarchy (Ancestors)

Immune System Diseases

Intervention Hierarchy (Ancestors)

Therapeutic Irrigation; Investigative Techniques

Study Officials

• Mitchell H Grayson, MD

  Nationwide Children's Hospital

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: January 26, 2017
• First Posted: February 1, 2017
• Study Start: September 6, 2017
• Primary Completion: July 16, 2018
• Study Completion: July 16, 2018
• Last Updated: October 7, 2019

Record last verified: 2019-10

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)