<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/NCT03023397</url>
  </required_header>
  <id_info>
    <org_study_id>16-1622</org_study_id>
    <secondary_id>P50HL120100-05</secondary_id>
    <nct_id>NCT03023397</nct_id>
  </id_info>
  <brief_title>Evaluation of the Effect of a Nasal Allergen Challenge With Dermatophagoides Farinae Extract on Nasal Airway Inflammation in Allergic Individuals, Comparing E-cigarette Users to Cigarette Smokers and Non-smokers.</brief_title>
  <acronym>Mitey Nose</acronym>
  <official_title>Evaluation of the Effect of a Nasal Allergen Challenge With Dermatophagoides Farinae Extract on Nasal Airway Inflammation in Allergic Individuals, Comparing E-cigarette Users to Cigarette Smokers and Non-smokers.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of North Carolina, Chapel Hill</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>University of North Carolina, Chapel Hill</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this pilot study is to evaluate allergen-induced nasal airway inflammation&#xD;
      following nasal application of Dermatophagoides farinae (Der f), or house dust mite, extract&#xD;
      in e-cigarette users, cigarette smokers, and non-smokers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The recent increase in popularity of e-cigarettes for smoking cessation or in combination&#xD;
      with conventional cigarettes has led to safety concerns regarding their potential role in&#xD;
      respiratory disease. These tobacco alternative devices were initially perceived as a &quot;safer&quot;&#xD;
      alternative to cigarettes and were marketed without much known about their health effects.&#xD;
      Increasing evidence demonstrates that while they contain fewer toxins and carcinogens than&#xD;
      conventional cigarettes, they do involve delivery of ultrafine particles to the lower airways&#xD;
      and can contain heavy metals and other chemicals. Tobacco smoke may augment allergic&#xD;
      inflammation resulting from allergic rhinitis and/or asthma. Animal models of allergic asthma&#xD;
      demonstrate aggravation of allergen-induced airway inflammation following inhalation of e-cig&#xD;
      cartridge solution, with increased airway eosinophil infiltration, production of Th2&#xD;
      cytokines, and airway hyperresponsivness. In vitro studies in human tissues have demonstrated&#xD;
      pro-inflammatory responses to e-cig vapour extract yet have not evaluated the effects of&#xD;
      e-cig usage on allergic inflammation in human airways. Current evidence suggests that&#xD;
      e-cigarette use augments allergic inflammatory responses in a similar way as tobacco smoke,&#xD;
      yet a head-to-head comparison of the effects of these two exposures has not been performed in&#xD;
      humans.&#xD;
&#xD;
      Use of tobacco products remains a pervasive problem in our society and around the world, with&#xD;
      significant impact on respiratory health and quality of life. With the emergence of new&#xD;
      non-tobacco based nicotine products like e-cigarettes, it is important to understand the&#xD;
      impact these substances have on respiratory health and disease. The aim of this study is to&#xD;
      study the impact of these products on allergic inflammation in house dust mite-allergic&#xD;
      subjects who already routinely use e-cigarettes and to compare their responses to those of&#xD;
      cigarette smokers and non-smokers. A thorough understanding of the potential health impacts&#xD;
      of tobacco alternative substances is needed, especially given the rising popularity of such&#xD;
      products with adolescents and young adults to whom these substances have particular appeal&#xD;
      given their purported &quot;safety&quot; and variety of flavors to choose from.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of funding&#xD;
  </why_stopped>
  <start_date type="Actual">March 27, 2017</start_date>
  <completion_date type="Actual">April 23, 2018</completion_date>
  <primary_completion_date type="Actual">April 16, 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Mean Change in Eosinophils Per mL in Nasal Lavage Fluid (NLF)</measure>
    <time_frame>Baseline, 4 hours post-allergen challenge</time_frame>
    <description>NLF will be collected immediately prior to administration of the nasal allergen challenge and 4 hours after completion of nasal allergen challenge. The protocol was amended to replace this outcome using Eosinophilic Cationic Protein (ECP) in Nasal Epithelial Lining Fluid (NELF).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean Change in Eosinophilic Cationic Protein (ECP) Levels in Nasal Epithelial Lining Fluid (NELF)</measure>
    <time_frame>baseline, 4 hours post-allergen challenge</time_frame>
    <description>NELF will be collected immediately prior to administration of the nasal allergen challenge and 4 hours after completion of nasal allergen challenge.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Change in Interleukin-31 (IL-31) Concentrations in NELF</measure>
    <time_frame>Pre- and 4 hours-post nasal allergen challenge</time_frame>
    <description>NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change in Interleukin-5 (IL-5) Concentrations in NELF</measure>
    <time_frame>baseline, 4 hours post-allergen challenge</time_frame>
    <description>NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change in Macrophage Inflammatory Protein 1 Alpha (MIP-1a) Concentration in NELF</measure>
    <time_frame>baseline, 4 hours post-allergen challenge</time_frame>
    <description>NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mean Change in Macrophage Inflammatory Protein 1 Beta (MIP-1b) in NELF</measure>
    <time_frame>baseline, 4 hours post-allergen challenge</time_frame>
    <description>NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Nasal Epithelial Cell Messenger Ribonucleic Acid (mRNA) Expression</measure>
    <time_frame>Baseline, 4 hours post- nasal allergen challenge</time_frame>
    <description>Nasal epithelial cell biopsies will be collected at baseline and 4 hours post- nasal allergen challenge. Gene expression changes will be quantified using quantitative real-time polymerase chain reaction (qRT-PCR).</description>
  </other_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Healthy Participants</condition>
  <condition>Tobacco Smokers</condition>
  <arm_group>
    <arm_group_label>Der f treated Non-smoker</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Der f treated Cigarette smoker</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Der f treated E-cig user</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Der f</intervention_name>
    <description>Nasal administration of Dermatophagoides farinae with 100 allergen units (AU), 500 AU, and finally 1000 AU</description>
    <arm_group_label>Der f treated Cigarette smoker</arm_group_label>
    <arm_group_label>Der f treated E-cig user</arm_group_label>
    <arm_group_label>Der f treated Non-smoker</arm_group_label>
    <other_name>(Der f)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Specific allergy to house dust mite D. farinae confirmed by positive immediate skin&#xD;
             test response&#xD;
&#xD;
          2. Subjects will either be non-asthmatic or have mild asthma characterized by an Forced&#xD;
             expiratory volume in one second (FEV1) of at least 80% of predicted to Forced vital&#xD;
             capacity (FVC) ratio of at least .75&#xD;
&#xD;
          3. Subjects will be classified as tobacco smokers, e-cigarette users, or non-smokers&#xD;
             according to the following guidelines.&#xD;
&#xD;
          4. Ability to withhold antihistamine medications for one week prior to baseline and&#xD;
             allergen challenge visits&#xD;
&#xD;
          5. Subjects must be able and willing to give informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any chronic medical condition considered by the PI as a contraindication to the&#xD;
             allergen challenge study including significant cardiovascular disease, diabetes&#xD;
             requiring medication, chronic renal disease, bleeding disorder, or chronic thyroid&#xD;
             disease.&#xD;
&#xD;
          2. Physician directed emergency treatment for an asthma exacerbation within the preceding&#xD;
             12 months.&#xD;
&#xD;
          3. Use of systemic steroid therapy within the preceding 12 months for treatment of an&#xD;
             asthma exacerbation.&#xD;
&#xD;
          4. Use of inhaled or nasal steroids, cromolyn or leukotriene receptor antagonists&#xD;
             (Montelukast or zafirlukast ) within the past month (except for use of cromolyn&#xD;
             exclusively prior to exercise).&#xD;
&#xD;
          5. Subjects who smoke marijuana or use illicit drugs will be excluded.&#xD;
&#xD;
          6. Use of daily theophylline within the past month.&#xD;
&#xD;
          7. Use of nasal medications that might alter the response to nasal allergen challenge&#xD;
             including anti-inflammatory and anti-histamine agents within one week of challenge.&#xD;
&#xD;
          8. Inability to withhold inhaled or oral bronchodilator medications for 12 hours prior to&#xD;
             allergen challenge.&#xD;
&#xD;
          9. Pregnancy or nursing a baby.&#xD;
&#xD;
         10. Women of child-bearing age who are not using dependable contraception (such as birth&#xD;
             control pills, intrauterine device (IUD), estrogen patches) or who are not completely&#xD;
             abstinent.&#xD;
&#xD;
         11. Nighttime symptoms of cough or wheeze greater than 1x/week at baseline (not during a&#xD;
             clearly recognized viral induced asthma exacerbation) which would be characteristic of&#xD;
             a person of moderate or severe persistent asthma as outlined in the current NHLBI&#xD;
             guidelines for diagnosis and management of asthma.&#xD;
&#xD;
         12. Exacerbation of asthma more than 2x/week which would be characteristic of a person&#xD;
             with moderate or severe persistent asthma as outlined in the current NHLBI guidelines&#xD;
             for diagnosis and management of asthma.&#xD;
&#xD;
         13. Daily requirement for albuterol due to asthma symptoms (cough, wheeze, chest&#xD;
             tightness) which would be characteristic of a person of moderate or severe persistent&#xD;
             asthma as outlined in the current NHLBI guidelines for diagnosis and management of&#xD;
             asthma. (Not to include prophylactic use of albuterol prior to exercise).&#xD;
&#xD;
         14. Viral upper respiratory tract infection or other acute inflammatory conditions of the&#xD;
             nose or paranasal sinuses, such as sinusitis, within 4 weeks of challenge.&#xD;
&#xD;
         15. Any acute infection requiring antibiotics within 4 weeks of challenge.&#xD;
&#xD;
         16. Participating in an allergen inhalation study within 2 weeks of this challenge or use&#xD;
             of any other investigational agent within the last 30 days.&#xD;
&#xD;
         17. Use of tricyclic antidepressants or beta-blockers.&#xD;
&#xD;
             -&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>50 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michelle Hernandez, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>UNC Center for Environmental Medicine, Asthma and Lung Biology</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599-7310</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>January 13, 2017</study_first_submitted>
  <study_first_submitted_qc>January 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 18, 2017</study_first_posted>
  <results_first_submitted>May 10, 2021</results_first_submitted>
  <results_first_submitted_qc>May 10, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">June 4, 2021</results_first_posted>
  <last_update_submitted>May 10, 2021</last_update_submitted>
  <last_update_submitted_qc>May 10, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">June 4, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>E-cig smokers</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 20, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/97/NCT03023397/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited from individuals who completed the general screening process at the Center for Environmental Medicine, Asthma and Lung Biology.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Non-smokers</title>
          <description>Non-smoking adults with a history of dust mite allergy and allergic rhinitis</description>
        </group>
        <group group_id="P2">
          <title>Cigarette Smokers</title>
          <description>Cigarette smoking adults with a history of dust mite allergy and allergic rhinitis</description>
        </group>
        <group group_id="P3">
          <title>E-cig Users</title>
          <description>E-cig using adults with a history of dust mite allergy and allergic rhinitis</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Run-In</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Failed screening allergen challenge</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Loss of funding after informed consent but before screening allergen challenge</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
        <period>
          <title>Main Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Non-smokers</title>
          <description>Non-smoking adults with a history of dust mite allergy and allergic rhinitis</description>
        </group>
        <group group_id="B2">
          <title>Cigarette Smokers</title>
          <description>Cigarette smoking adults with a history of dust mite allergy and allergic rhinitis</description>
        </group>
        <group group_id="B3">
          <title>E-cig Users</title>
          <description>E-cig using adults with a history of dust mite allergy and allergic rhinitis</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="8"/>
            <count group_id="B2" value="3"/>
            <count group_id="B3" value="1"/>
            <count group_id="B4" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Age</title>
          <units>Years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="29.6" lower_limit="20.1" upper_limit="35"/>
                    <measurement group_id="B2" value="34.6" lower_limit="28.5" upper_limit="41.1"/>
                    <measurement group_id="B3" value="21.4" lower_limit="21.4" upper_limit="21.4"/>
                    <measurement group_id="B4" value="29" lower_limit="20.1" upper_limit="41.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="1"/>
                    <measurement group_id="B4" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Mean Change in Eosinophils Per mL in Nasal Lavage Fluid (NLF)</title>
        <description>NLF will be collected immediately prior to administration of the nasal allergen challenge and 4 hours after completion of nasal allergen challenge. The protocol was amended to replace this outcome using Eosinophilic Cationic Protein (ECP) in Nasal Epithelial Lining Fluid (NELF).</description>
        <time_frame>Baseline, 4 hours post-allergen challenge</time_frame>
        <population>NLF samples obtained from six non-smokers, 3 smokers and 1 e-cig user were contaminated with blood and therefore were not suitable samples for analysis of nasal inflammatory cells. The protocol was changed to include eosinophilic cationic protein (ECP) in nasal epithelial lining fluid (NELF) as the primary outcome measure.</population>
        <group_list>
          <group group_id="O1">
            <title>Non-smokers</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a total nasal symptom score (TNSS) of 8 or more AND a reduction in peak nasal inspiratory flow (PNIF) of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
          <group group_id="O2">
            <title>Cigarette Smokers</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
          <group group_id="O3">
            <title>E-cig Users</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Eosinophils Per mL in Nasal Lavage Fluid (NLF)</title>
          <description>NLF will be collected immediately prior to administration of the nasal allergen challenge and 4 hours after completion of nasal allergen challenge. The protocol was amended to replace this outcome using Eosinophilic Cationic Protein (ECP) in Nasal Epithelial Lining Fluid (NELF).</description>
          <population>NLF samples obtained from six non-smokers, 3 smokers and 1 e-cig user were contaminated with blood and therefore were not suitable samples for analysis of nasal inflammatory cells. The protocol was changed to include eosinophilic cationic protein (ECP) in nasal epithelial lining fluid (NELF) as the primary outcome measure.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Mean Change in Eosinophilic Cationic Protein (ECP) Levels in Nasal Epithelial Lining Fluid (NELF)</title>
        <description>NELF will be collected immediately prior to administration of the nasal allergen challenge and 4 hours after completion of nasal allergen challenge.</description>
        <time_frame>baseline, 4 hours post-allergen challenge</time_frame>
        <population>Six non-smoking participants, 3 smoking participants and 1 e-cig using participant had paired pre and 4 hours post-challenge samples for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Non-smokers</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
          <group group_id="O2">
            <title>Cigarette Smokers</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
          <group group_id="O3">
            <title>E-cig Users</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Eosinophilic Cationic Protein (ECP) Levels in Nasal Epithelial Lining Fluid (NELF)</title>
          <description>NELF will be collected immediately prior to administration of the nasal allergen challenge and 4 hours after completion of nasal allergen challenge.</description>
          <population>Six non-smoking participants, 3 smoking participants and 1 e-cig using participant had paired pre and 4 hours post-challenge samples for analysis.</population>
          <units>micrograms/L</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="31374" spread="37261"/>
                    <measurement group_id="O2" value="-50847" spread="45535"/>
                    <measurement group_id="O3" value="-17851" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change in Interleukin-31 (IL-31) Concentrations in NELF</title>
        <description>NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.</description>
        <time_frame>Pre- and 4 hours-post nasal allergen challenge</time_frame>
        <population>Six non-smoking participants, 3 smoking participants and 1 e-cig using participant had paired pre and 4 hours post-challenge samples for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Non-smokers</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
          <group group_id="O2">
            <title>Cigarette Smokers</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
          <group group_id="O3">
            <title>E-cig Users</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Interleukin-31 (IL-31) Concentrations in NELF</title>
          <description>NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.</description>
          <population>Six non-smoking participants, 3 smoking participants and 1 e-cig using participant had paired pre and 4 hours post-challenge samples for analysis.</population>
          <units>picograms/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.76" spread="1.01"/>
                    <measurement group_id="O2" value="0.06" spread="0.28"/>
                    <measurement group_id="O3" value="4.76" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change in Interleukin-5 (IL-5) Concentrations in NELF</title>
        <description>NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.</description>
        <time_frame>baseline, 4 hours post-allergen challenge</time_frame>
        <population>Six non-smoking participants, 3 smoking participants and 1 e-cig using participant had paired pre and 4 hours post-challenge samples for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Non-smokers</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
          <group group_id="O2">
            <title>Cigarette Smokers</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
          <group group_id="O3">
            <title>E-cig Users</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Interleukin-5 (IL-5) Concentrations in NELF</title>
          <description>NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.</description>
          <population>Six non-smoking participants, 3 smoking participants and 1 e-cig using participant had paired pre and 4 hours post-challenge samples for analysis.</population>
          <units>picograms/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="75.82" spread="53.02"/>
                    <measurement group_id="O2" value="3.42" spread="4.58"/>
                    <measurement group_id="O3" value="240.9" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change in Macrophage Inflammatory Protein 1 Alpha (MIP-1a) Concentration in NELF</title>
        <description>NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.</description>
        <time_frame>baseline, 4 hours post-allergen challenge</time_frame>
        <population>Six non-smoking participants, 3 smoking participants and 1 e-cig using participant had paired pre and 4 hours post-challenge samples for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Non-smokers</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
          <group group_id="O2">
            <title>Cigarette Smokers</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
          <group group_id="O3">
            <title>E-cig Users</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Macrophage Inflammatory Protein 1 Alpha (MIP-1a) Concentration in NELF</title>
          <description>NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.</description>
          <population>Six non-smoking participants, 3 smoking participants and 1 e-cig using participant had paired pre and 4 hours post-challenge samples for analysis.</population>
          <units>picograms/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="72.52" spread="42.9"/>
                    <measurement group_id="O2" value="10.04" spread="8.03"/>
                    <measurement group_id="O3" value="91.43" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Change in Macrophage Inflammatory Protein 1 Beta (MIP-1b) in NELF</title>
        <description>NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.</description>
        <time_frame>baseline, 4 hours post-allergen challenge</time_frame>
        <population>Six non-smoking participants, 3 smoking participants and 1 e-cig using participant had paired pre and 4 hours post-challenge samples for analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>Non-smokers</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
          <group group_id="O2">
            <title>Cigarette Smokers</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
          <group group_id="O3">
            <title>E-cig Users</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Change in Macrophage Inflammatory Protein 1 Beta (MIP-1b) in NELF</title>
          <description>NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.</description>
          <population>Six non-smoking participants, 3 smoking participants and 1 e-cig using participant had paired pre and 4 hours post-challenge samples for analysis.</population>
          <units>picograms/mL</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="3"/>
                <count group_id="O3" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="370.8" spread="511.6"/>
                    <measurement group_id="O2" value="18.97" spread="12.01"/>
                    <measurement group_id="O3" value="32.98" spread="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Nasal Epithelial Cell Messenger Ribonucleic Acid (mRNA) Expression</title>
        <description>Nasal epithelial cell biopsies will be collected at baseline and 4 hours post- nasal allergen challenge. Gene expression changes will be quantified using quantitative real-time polymerase chain reaction (qRT-PCR).</description>
        <time_frame>Baseline, 4 hours post- nasal allergen challenge</time_frame>
        <population>No samples were analyzed due to lack of funding and early termination of the study</population>
        <group_list>
          <group group_id="O1">
            <title>Non-smokers</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
          <group group_id="O2">
            <title>Cigarette Smokers</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
          <group group_id="O3">
            <title>E-cig Users</title>
            <description>Intranasal administration of Dermatophagoides farinae allergen is performed until the participant reaches a TNSS of 8 or more AND a reduction in PNIF of 20% or more (or until the highest allergen dose is administered).</description>
          </group>
        </group_list>
        <measure>
          <title>Nasal Epithelial Cell Messenger Ribonucleic Acid (mRNA) Expression</title>
          <description>Nasal epithelial cell biopsies will be collected at baseline and 4 hours post- nasal allergen challenge. Gene expression changes will be quantified using quantitative real-time polymerase chain reaction (qRT-PCR).</description>
          <population>No samples were analyzed due to lack of funding and early termination of the study</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From the time of informed consent to the final study visit (up to 6 months).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Non-smoker</title>
          <description>Non-smoking adults with a history of dust mite allergy and allergic rhinitis</description>
        </group>
        <group group_id="E2">
          <title>Cigarette Smoker</title>
          <description>Cigarette smoking adults with a history of dust mite allergy and allergic rhinitis</description>
        </group>
        <group group_id="E3">
          <title>E-cig User</title>
          <description>E-cig using adults with a history of dust mite allergy and allergic rhinitis</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="8"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" subjects_affected="1" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Epistaxis</sub_title>
                <description>Mild epistaxis post nasal lavage administration - self resolved.</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <description>Headache post nasal allergen challenge</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Rhinitis</sub_title>
                <description>Continued rhinitis experienced within 96 hours of nasal allergen challenge</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="1" subjects_affected="1" subjects_at_risk="1"/>
              </event>
              <event>
                <sub_title>Sneeze</sub_title>
                <description>Continued sneezing within 96 hours of nasal allergen challenge</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Respiratory, thoracic and mediastinal disorders</title>
            <event_list>
              <event>
                <sub_title>Cough</sub_title>
                <assessment>Non-systematic Assessment</assessment>
                <description>non-productive cough 30 minutes post nasal allergen challenge administration</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="8"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="3"/>
                <counts group_id="E3" events="0" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Allison Burbank, MD</name_or_title>
      <organization>University of North Carolina at Chapel Hill</organization>
      <phone>919-962-5136</phone>
      <email>allison_burbank@med.unc.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03023397
org study id: 16-1622
secondary id: P50HL120100-05
nct id: NCT03023397
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: Yes
is fda regulated device: No
The purpose of this pilot study is to evaluate allergen-induced nasal airway inflammation
      following nasal application of Dermatophagoides farinae (Der f), or house dust mite, extract
      in e-cigarette users, cigarette smokers, and non-smokers.
The recent increase in popularity of e-cigarettes for smoking cessation or in combination
      with conventional cigarettes has led to safety concerns regarding their potential role in
      respiratory disease. These tobacco alternative devices were initially perceived as a "safer"
      alternative to cigarettes and were marketed without much known about their health effects.
      Increasing evidence demonstrates that while they contain fewer toxins and carcinogens than
      conventional cigarettes, they do involve delivery of ultrafine particles to the lower airways
      and can contain heavy metals and other chemicals. Tobacco smoke may augment allergic
      inflammation resulting from allergic rhinitis and/or asthma. Animal models of allergic asthma
      demonstrate aggravation of allergen-induced airway inflammation following inhalation of e-cig
      cartridge solution, with increased airway eosinophil infiltration, production of Th2
      cytokines, and airway hyperresponsivness. In vitro studies in human tissues have demonstrated
      pro-inflammatory responses to e-cig vapour extract yet have not evaluated the effects of
      e-cig usage on allergic inflammation in human airways. Current evidence suggests that
      e-cigarette use augments allergic inflammatory responses in a similar way as tobacco smoke,
      yet a head-to-head comparison of the effects of these two exposures has not been performed in
      humans.

      Use of tobacco products remains a pervasive problem in our society and around the world, with
      significant impact on respiratory health and quality of life. With the emergence of new
      non-tobacco based nicotine products like e-cigarettes, it is important to understand the
      impact these substances have on respiratory health and disease. The aim of this study is to
      study the impact of these products on allergic inflammation in house dust mite-allergic
      subjects who already routinely use e-cigarettes and to compare their responses to those of
      cigarette smokers and non-smokers. A thorough understanding of the potential health impacts
      of tobacco alternative substances is needed, especially given the rising popularity of such
      products with adolescents and young adults to whom these substances have particular appeal
      given their purported "safety" and variety of flavors to choose from.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Mean Change in Eosinophils Per mL in Nasal Lavage Fluid (NLF)
time frame: Baseline, 4 hours post-allergen challenge
description: NLF will be collected immediately prior to administration of the nasal allergen challenge and 4 hours after completion of nasal allergen challenge. The protocol was amended to replace this outcome using Eosinophilic Cationic Protein (ECP) in Nasal Epithelial Lining Fluid (NELF).
measure: Mean Change in Eosinophilic Cationic Protein (ECP) Levels in Nasal Epithelial Lining Fluid (NELF)
time frame: baseline, 4 hours post-allergen challenge
description: NELF will be collected immediately prior to administration of the nasal allergen challenge and 4 hours after completion of nasal allergen challenge.
measure: Mean Change in Interleukin-31 (IL-31) Concentrations in NELF
time frame: Pre- and 4 hours-post nasal allergen challenge
description: NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.
measure: Mean Change in Interleukin-5 (IL-5) Concentrations in NELF
time frame: baseline, 4 hours post-allergen challenge
description: NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.
measure: Mean Change in Macrophage Inflammatory Protein 1 Alpha (MIP-1a) Concentration in NELF
time frame: baseline, 4 hours post-allergen challenge
description: NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.
measure: Mean Change in Macrophage Inflammatory Protein 1 Beta (MIP-1b) in NELF
time frame: baseline, 4 hours post-allergen challenge
description: NELF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post- nasal allergen challenge.
measure: Nasal Epithelial Cell Messenger Ribonucleic Acid (mRNA) Expression
time frame: Baseline, 4 hours post- nasal allergen challenge
description: Nasal epithelial cell biopsies will be collected at baseline and 4 hours post- nasal allergen challenge. Gene expression changes will be quantified using quantitative real-time polymerase chain reaction (qRT-PCR).
arm group label: Der f treated Non-smoker
arm group type: Other
arm group label: Der f treated Cigarette smoker
arm group type: Other
arm group label: Der f treated E-cig user
arm group type: Other
intervention type: Biological
intervention name: Der f
description: Nasal administration of Dermatophagoides farinae with 100 allergen units (AU), 500 AU, and finally 1000 AU
arm group label: Der f treated Cigarette smoker
arm group label: Der f treated E-cig user
arm group label: Der f treated Non-smoker
other name: (Der f)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 50 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Michelle Hernandez, MD
role: Principal Investigator
affiliation: University of North Carolina
facility: 
country: United States
responsible party type: Sponsor
mesh term: Inflammation
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 