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Leukotriene Antagonism in Recruitment of CD49d Expressing Neutrophils in Atopic Subjects

Primary Purpose

Nasal Allergy

Status

Completed

Phase

Not Applicable

Locations

United States

Study Type

Interventional

Intervention

Nasal lavage

Nasal allergen challenge

Epicutaneous skin testing

Peripheral blood

Montelukast 10Mg Tablet

Placebo Oral Tablet

About this trial

This is an interventional basic science trial for Nasal Allergy focused on measuring allergen, neutrophils, allergy

Eligibility Criteria

21 Years - 65 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

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

Sites / Locations

Nationwide Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

Montelukast

Placebo

Arm Description

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

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.

Outcomes

Primary Outcome Measures

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.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT03039101

First Posted

January 26, 2017

Last Updated

October 3, 2019

Sponsor

Mitchell Grayson

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

1. Study Identification

Unique Protocol Identification Number

NCT03039101

Brief Title

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

2. Study Status

Record Verification Date

October 2019

Overall Recruitment Status

Completed

Study Start Date

September 6, 2017 (Actual)

Primary Completion Date

July 16, 2018 (Actual)

Study Completion Date

July 16, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor-Investigator

Name of the Sponsor

Mitchell Grayson

Collaborators

National Heart, Lung, and Blood Institute (NHLBI)

4. Oversight

Studies a U.S. FDA-regulated Drug Product

Studies a U.S. FDA-regulated Device Product

Data Monitoring Committee

5. Study Description

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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Nasal Allergy

Keywords

allergen, neutrophils, allergy

7. Study Design

Primary Purpose

Basic Science

Study Phase

Not Applicable

Interventional Study Model

Crossover Assignment

Masking

ParticipantCare ProviderInvestigatorOutcomes Assessor

Allocation

Randomized

Enrollment

25 (Actual)

8. Arms, Groups, and Interventions

Arm Title

Montelukast

Arm Type

Experimental

Arm Description

Arm Title

Placebo

Arm Type

Placebo Comparator

Arm Description

Intervention Type

Procedure

Intervention Name(s)

Nasal lavage

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

Nasal allergen challenge

Intervention Description

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

Intervention Type

Procedure

Intervention Name(s)

Epicutaneous skin testing

Intervention Description

Skin testing (prick) to determine allergies.

Intervention Type

Procedure

Intervention Name(s)

Peripheral blood

Intervention Description

Peripheral blood draw

Intervention Type

Drug

Intervention Name(s)

Montelukast 10Mg Tablet

Other Intervention Name(s)

montelukast

Intervention Description

one pill orally, daily, for 1 week

Intervention Type

Drug

Intervention Name(s)

Placebo Oral Tablet

Other Intervention Name(s)

placebo

Intervention Description

one pill orally, daily, for 1 week

Primary Outcome Measure Information:

Title

Change in frequency in CD49d+ neutrophils in the nasal lavage post-allergen challenge on placebo versus Montelukast.

Description

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.

Time Frame

1 month

Secondary Outcome Measure Information:

Title

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

Description

Time Frame

1 month

Other Pre-specified Outcome Measures:

Title

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

Description

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).

Time Frame

1 month

10. Eligibility

Sex

All

Minimum Age & Unit of Time

21 Years

Maximum Age & Unit of Time

65 Years

Accepts Healthy Volunteers

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

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Mitchell H Grayson, MD

Organizational Affiliation

Nationwide Children's Hospital

Official's Role

Principal Investigator

Facility Information:

Facility Name

Nationwide Children's Hospital

City

Columbus

State/Province

Ohio

ZIP/Postal Code

43205

Country

United States

12. IPD Sharing Statement

Plan to Share IPD

Citations:

PubMed Identifier

24360325

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.

Results Reference

background

PubMed Identifier

20876348

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.

Results Reference

background

PubMed Identifier

19962743

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.

Results Reference

background

PubMed Identifier

19620293

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.

Results Reference

background

PubMed Identifier

21130381

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.

Results Reference

background

PubMed Identifier

17954569

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.

Results Reference

background

PubMed Identifier

7700748

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.

Results Reference

background

PubMed Identifier

31491537

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.

Results Reference

result

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Leukotriene Antagonism in Recruitment of CD49d Expressing Neutrophils in Atopic Subjects

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