<clinical_study>
  <!-- This xml conforms to an XML Schema at:
    https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
  <required_header>
    <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
    <link_text>Link to the current ClinicalTrials.gov record.</link_text>
    <url>https://clinicaltrials.gov/ct2/show/NCT03039101</url>
  </required_header>
  <id_info>
    <org_study_id>IRB16-00842</org_study_id>
    <secondary_id>R01HL087778</secondary_id>
    <nct_id>NCT03039101</nct_id>
  </id_info>
  <brief_title>Leukotriene Antagonism in Recruitment of CD49d Expressing Neutrophils in Atopic Subjects</brief_title>
  <official_title>Double Blind Study of Leukotriene Antagonism in the Nasal Recruitment of CD49d Expressing Neutrophils in Atopic Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Mitchell Grayson</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Nationwide Children's Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to see if the recruitment of a certain cell type (the alpha 4&#xD;
      integrin (CD49d) expressing neutrophil) during a nasal allergen challenge can be inhibited by&#xD;
      pretreatment with an FDA approved leukotriene antagonist (montelukast).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects will be consented, undergo skin testing, medical history questionnaires, and&#xD;
      randomized to either placebo or montelukast (10 mg). In one week, subjects return, undergo a&#xD;
      blood draw, medical history questionnaires, nasal lavage, and nasal allergen challenge&#xD;
      (followed by lavage in 6 hours). Subjects will then cross-over to the other study drug. One&#xD;
      week later subjects will undergo a blood draw, medical history questionnaires, lavage,&#xD;
      allergen challenge, and repeat lavage (after 6 hours).&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 6, 2017</start_date>
  <completion_date type="Actual">July 16, 2018</completion_date>
  <primary_completion_date type="Actual">July 16, 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in frequency in CD49d+ neutrophils in the nasal lavage post-allergen challenge on placebo versus Montelukast.</measure>
    <time_frame>1 month</time_frame>
    <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.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in clinical response following nasal allergen challenge after one week of treatment with Montelukast.</measure>
    <time_frame>1 month</time_frame>
    <description>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.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Induction of expression of immunoglobulin E (IgE) receptor on dendritic cells following exposure with CD49d+ cells from peripheral blood samples.</measure>
    <time_frame>1 month</time_frame>
    <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).</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">25</enrollment>
  <condition>Nasal Allergy</condition>
  <arm_group>
    <arm_group_label>Montelukast</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <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</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Placebo</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>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.</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Nasal lavage</intervention_name>
    <description>determine frequency of CD49d expressing neutrophils in the nasal lavage by flow cytometry</description>
    <arm_group_label>Montelukast</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Nasal allergen challenge</intervention_name>
    <description>A small amount of allergen extract will be applied to one naris.</description>
    <arm_group_label>Montelukast</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Epicutaneous skin testing</intervention_name>
    <description>Skin testing (prick) to determine allergies.</description>
    <arm_group_label>Montelukast</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Peripheral blood</intervention_name>
    <description>Peripheral blood draw</description>
    <arm_group_label>Montelukast</arm_group_label>
    <arm_group_label>Placebo</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Montelukast 10Mg Tablet</intervention_name>
    <description>one pill orally, daily, for 1 week</description>
    <arm_group_label>Montelukast</arm_group_label>
    <other_name>montelukast</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Oral Tablet</intervention_name>
    <description>one pill orally, daily, for 1 week</description>
    <arm_group_label>Placebo</arm_group_label>
    <other_name>placebo</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  21 - 65 years of age, inclusive&#xD;
&#xD;
          -  A personal history of allergic rhinitis (hayfever) (by self-report)&#xD;
&#xD;
          -  At least one positive skin test to cat, dust mite mix, Timothy grass, Bermuda grass,&#xD;
             Bluegrass, or Ragweed&#xD;
&#xD;
          -  Ability to provide informed consent&#xD;
&#xD;
          -  Willingness to undergo epicutaneous skin testing&#xD;
&#xD;
          -  Willingness to undergo nasal lavages and nasal allergen challenges&#xD;
&#xD;
          -  Willingness to undergo 2 peripheral blood draws (10 cc each)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Use of systemic antihistamine in the past 5 days&#xD;
&#xD;
          -  Use of intranasal corticosteroids or intranasal antihistamines currently or in the&#xD;
             past 2 weeks&#xD;
&#xD;
          -  Use of Montelukast currently or in the past week&#xD;
&#xD;
          -  Hypersensitivity or allergy to Montelukast&#xD;
&#xD;
          -  Inability to perform/undergo any study procedures&#xD;
&#xD;
          -  Pregnancy (by subject report) or breastfeeding&#xD;
&#xD;
          -  Confirmed or suspected immunodeficiency&#xD;
&#xD;
          -  Persistent asthma, atopic dermatitis, or any other co-morbid disease except for&#xD;
             allergic rhinitis&#xD;
&#xD;
          -  Any symptoms of asthma in the past 2 weeks (shortness of breath, wheezing, and/or use&#xD;
             of albuterol)&#xD;
&#xD;
          -  Fever (temperature over 99F) currently or in the past 2 weeks&#xD;
&#xD;
          -  Current or previous use of a biologic or investigational agent in the past 6 months&#xD;
&#xD;
          -  Current or past suicidal thoughts/attempts&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mitchell H Grayson, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Nationwide Children's Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nationwide Children's Hospital</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43205</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <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>
    <PMID>24360325</PMID>
  </reference>
  <reference>
    <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>
    <PMID>20876348</PMID>
  </reference>
  <reference>
    <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>
    <PMID>19962743</PMID>
  </reference>
  <reference>
    <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>
    <PMID>19620293</PMID>
  </reference>
  <reference>
    <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>
    <PMID>21130381</PMID>
  </reference>
  <reference>
    <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>
    <PMID>17954569</PMID>
  </reference>
  <reference>
    <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>
    <PMID>7700748</PMID>
  </reference>
  <results_reference>
    <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.</citation>
    <PMID>31491537</PMID>
  </results_reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>January 26, 2017</study_first_submitted>
  <study_first_submitted_qc>January 30, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">February 1, 2017</study_first_posted>
  <last_update_submitted>October 3, 2019</last_update_submitted>
  <last_update_submitted_qc>October 3, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 7, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Nationwide Children's Hospital</investigator_affiliation>
    <investigator_full_name>Mitchell Grayson</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>allergen</keyword>
  <keyword>neutrophils</keyword>
  <keyword>allergy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Hypersensitivity</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Montelukast</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03039101
org study id: IRB16-00842
secondary id: R01HL087778
nct id: NCT03039101
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
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).
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).
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
measure: Change in frequency in CD49d+ neutrophils in the nasal lavage post-allergen challenge on placebo versus Montelukast.
time frame: 1 month
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.
measure: Change in clinical response following nasal allergen challenge after one week of treatment with Montelukast.
time frame: 1 month
description: 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.
measure: Induction of expression of immunoglobulin E (IgE) receptor on dendritic cells following exposure with CD49d+ cells from peripheral blood samples.
time frame: 1 month
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).
arm group label: Montelukast
arm group type: Experimental
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
arm group label: Placebo
arm group type: Placebo Comparator
description: 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.
intervention type: Procedure
intervention name: Nasal lavage
description: determine frequency of CD49d expressing neutrophils in the nasal lavage by flow cytometry
arm group label: Montelukast
arm group label: Placebo
intervention type: Procedure
intervention name: Nasal allergen challenge
description: A small amount of allergen extract will be applied to one naris.
arm group label: Montelukast
arm group label: Placebo
intervention type: Procedure
intervention name: Epicutaneous skin testing
description: Skin testing (prick) to determine allergies.
arm group label: Montelukast
intervention type: Procedure
intervention name: Peripheral blood
description: Peripheral blood draw
arm group label: Montelukast
arm group label: Placebo
intervention type: Drug
intervention name: Montelukast 10Mg Tablet
description: one pill orally, daily, for 1 week
arm group label: Montelukast
other name: montelukast
intervention type: Drug
intervention name: Placebo Oral Tablet
description: one pill orally, daily, for 1 week
arm group label: Placebo
other name: placebo
criteria: 
gender: All
minimum age: 21 Years
maximum age: 65 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Mitchell H Grayson, MD
role: Principal Investigator
affiliation: Nationwide Children's Hospital
facility: 
country: United States
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.
PMID: 24360325
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.
PMID: 20876348
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.
PMID: 19962743
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.
PMID: 19620293
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.
PMID: 21130381
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.
PMID: 17954569
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.
PMID: 7700748
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.
PMID: 31491537
responsible party type: Sponsor-Investigator
investigator affiliation: Nationwide Children's Hospital
investigator full name: Mitchell Grayson
investigator title: Principal Investigator
mesh term: Hypersensitivity
mesh term: Montelukast
sharing ipd: No