<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/NCT03780387</url>
  </required_header>
  <id_info>
    <org_study_id>18-2006</org_study_id>
    <secondary_id>1R01HL135235-01A1</secondary_id>
    <nct_id>NCT03780387</nct_id>
  </id_info>
  <brief_title>Identification of Allergic Asthmatics Reactive to Felis Catus (Cat Hair) Allergen Inhalation</brief_title>
  <official_title>Identification of Allergic Asthmatics Reactive to Felis Catus (Cat Hair) Allergen Inhalation</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>Yes</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>
      This study is designed to identify Felis Catus, or cat hair, sensitive asthmatics who&#xD;
      demonstrate a late phase asthmatic response after cat hair inhalation. These subjects may be&#xD;
      invited to participate in a planned future study investigating novel asthma treatments.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Asthma is an increasingly common chronic illness among children and adults, and allergen&#xD;
      exposure is among the most common triggers for asthma exacerbations. Exacerbations of&#xD;
      allergic asthma are characterized by an early phase response (EPR), mediated by release of&#xD;
      preformed mediators like histamine from mast cells, and a late phase response (LPR) 3-7 hours&#xD;
      later mediated by chemokines and cytokines that attract leukocytes such as neutrophils and&#xD;
      eosinophils to the airways, increase mucus production, trigger airway smooth muscle&#xD;
      contraction, and result in airway constriction and airway hyperreactivity (AHR). The LPR does&#xD;
      not occur in the absence of an EPR. The LPR is thought to be predominantly responsible for&#xD;
      the symptoms associated with acute exacerbations of allergic asthma and is often used as the&#xD;
      measure of efficacy in trials of asthma therapeutics.&#xD;
&#xD;
      This group has taken a particular interest in targeting an inflammatory cytokine,&#xD;
      Interleukin-1β, involved in both the early and late phase asthmatic responses to inhaled&#xD;
      allergen in allergic asthmatics. In the lung, interleukin 1 beta (IL-1β) is produced by&#xD;
      numerous cell types (including epithelial cells, macrophages, neutrophils, eosinophils, and&#xD;
      mast cells), where it signals through its receptor to induce transcription of&#xD;
      pro-inflammatory genes (17-19). IL-1β is increased in bronchoalveolar lavage fluid from&#xD;
      persons with symptomatic asthma vs. those with asymptomatic asthma; likewise,&#xD;
      immunohistochemistry of bronchial biopsies of allergic asthmatics reveal increased expression&#xD;
      of IL-1β in both bronchial epithelial cells and macrophages.&#xD;
&#xD;
      In order to better understand the role of IL-1β in allergen-induced airway inflammation,&#xD;
      induced sputum will be obtained to determine if higher baseline sputum IL-1β concentrations&#xD;
      or larger increases in IL-1β following allergen challenge impact non-specific airway&#xD;
      hyperresponsiveness (via methacholine challenge), sputum granulocyte recruitment (neutrophil&#xD;
      and eosinophil counts and exhaled nitric oxide (eNO), a marker of airway eosinophilia), or&#xD;
      changes in expression of inflammatory or allergy-related genes. To this last point, little is&#xD;
      known about the mechanisms contributing to response patterns in allergic asthmatics&#xD;
      undergoing allergen challenge. Changes in gene expression occurring during the window of time&#xD;
      between the EPR and LPR, as these expression changes may dictate whether or not a LPR occurs&#xD;
      or to what extent it occurs.&#xD;
&#xD;
      The goal of this screening protocol is to identify subjects who exhibit both an EPR and LPR&#xD;
      and who will be eligible for enrollment in the yet to be developed IL-1β protocols. Subjects&#xD;
      will undergo a baseline methacholine challenge to establish reactivity, then allergen&#xD;
      exposure, followed 24 hours later by methacholine challenge.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Terminated due to COVID-19 pandemic.&#xD;
  </why_stopped>
  <start_date type="Actual">April 16, 2019</start_date>
  <completion_date type="Actual">November 11, 2019</completion_date>
  <primary_completion_date type="Actual">November 11, 2019</primary_completion_date>
  <phase>Early Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Maximum Change in the Percentage of Forced Expiratory Volume in 1 Second (FEV1)</measure>
    <time_frame>Pre-challenge to 10 hours post-challenge</time_frame>
    <description>Pre-challenge FEV1 is measured just prior to administration of the allergen challenge. FEV1 is measured at regular intervals for 10 hours after the challenge. [(Lowest FEV1 value post-challenge - Pre-challenge FEV1 value)/(Pre-challenge FEV1 value)]*100</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Levels of IL-1β in Induced Sputum</measure>
    <time_frame>Baseline and 24 hours post- inhalation challenge</time_frame>
    <description>Participants will undergo a hypertonic saline induced sputum procedure at baseline (within ~2 weeks of the allergen challenge), and again at 24 hours following inhaled allergen challenge. IL-1β concentrations in the sputum will be determined via ELISA. In addition to assessing changes in IL-1β levels, we will determine if IL-1β levels are predictive of key asthma outcomes following inhaled allergen challenge (see outcomes 3-7).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in the Percentage of Sputum Eosinophils</measure>
    <time_frame>Pre-challenge and 24 hours post-challenge</time_frame>
    <description>Induced sputum obtained pre-challenge and again at 24 hours post-challenge will be assessed for cells. (% eosinophils post-challenge - %eosinophils pre-challenge)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mucins in Sputum</measure>
    <time_frame>Baseline and 24 hours post- inhalation challenge</time_frame>
    <description>Sputum mucins will be measured at baseline, and again at 24 hours following inhaled allergen challenge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants Who Experience a Late Phase Response (Fall in FEV1≥15%) to Inhaled Allergen</measure>
    <time_frame>Pre-challenge to 10 hours post-challenge</time_frame>
    <description>FEV1 will be measured prior to administration of the inhaled allergen challenge. The maximum drop in FEV1 that occurs during the late phase (3-10 hours after challenge) will be determined.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Airway Hyperresponsiveness Measured by Difference in Methacholine Dose Required to Produce a ≥20% Fall in FEV1 (PC20)</measure>
    <time_frame>Baseline to 24 hours post-challenge</time_frame>
    <description>Participants will undergo a methacholine challenge to assess airway hyper-responsiveness at baseline. Changes in methacholine reactivity from baseline to 24 hours post-allergen challenge will be determined. Negative values indicate decrease and positive values indicate increase in doubling. (methacholine PC20 post-challenge - methacholine PC20 pre-challenge).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Exhaled Nitric Oxide (eNO) Levels in Ppb</measure>
    <time_frame>Pre-challenge to 24 hours post-challenge</time_frame>
    <description>eNO levels will be measured pre-challenge, and 24 hours post-challenge. (eNO value post-challenge - eNO value pre-challenge)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Heart Rate Variability (HRV)</measure>
    <time_frame>Pre challenge and immediately post challenge</time_frame>
    <description>HRV with Spacelabs technology will be measured 24 hours pre and during inhalation challenge</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Concentration of Inflammatory Cytokines in Nasal Epithelial Lining Fluid</measure>
    <time_frame>Pre challenge and immediately post challenge</time_frame>
    <description>Nasal fluid collected for analysis of cytokines IL-8, IL-6, IL-1alpha, IL-1 beta. [(Cytokine concentration immediately post-challenge) - (cytokine concentration pre-challenge)].</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Concentration of Inflammatory Cytokines in Nasal Epithelial Lining Fluid</measure>
    <time_frame>Pre challenge and 7 hours post challenge</time_frame>
    <description>Nasal strip to collect cytokines IL-8, IL-6, IL-1alpha, IL-1 beta. [(Cytokine concentration 7h post-challenge) - (cytokine concentration pre-challenge)].</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Concentration of Inflammatory Cytokines in Nasal Epithelial Lining Fluid</measure>
    <time_frame>Pre challenge and 24 hours post challenge</time_frame>
    <description>Nasal strip to collect cytokine IL-8, IL-6, IL-1alpha, IL-1 beta. [(Cytokine concentration 24h post-challenge) - (cytokine concentration pre-challenge)].</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Asthma Atopic</condition>
  <arm_group>
    <arm_group_label>Inhaled Allergen Challenge</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Felis Catus sensitive, mild asthmatics will undergo inhaled allergen challenge.</description>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Felis Catus</intervention_name>
    <description>Inhalation of Felis Catus allergen in subjects allergic to Felis Catus</description>
    <arm_group_label>Inhaled Allergen Challenge</arm_group_label>
    <other_name>Cat hair</other_name>
    <other_name>Cat</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age range 18-45 years, inclusive&#xD;
&#xD;
          -  FEV1 of at least 80% of predicted and FEV1/FVC (Forced Vital Capacity) ratio of at&#xD;
             least 0.7 (without use of bronchodilator medications for 8 hours or long acting beta&#xD;
             agonists for 24 hours), consistent with lung function of persons with no more than&#xD;
             mild episodic or mild persistent asthma.&#xD;
&#xD;
          -  Physician diagnosis of asthma&#xD;
&#xD;
          -  Allergic sensitization to felis catus (cat hair) as confirmed by positive immediate&#xD;
             skin prick test response&#xD;
&#xD;
          -  Negative pregnancy test for females who are not s/p hysterectomy or who have been&#xD;
             amenorrheic for 12 months or more.&#xD;
&#xD;
          -  Oxygen saturation of &gt;94% and blood pressure within the following limits: (Systolic&#xD;
             between 150-90 mmHg, Diastolic between 90-60 mmHg).&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Clinical contraindications:&#xD;
&#xD;
          -  Any chronic medical condition considered by the PI as a contraindication to&#xD;
             participation in the study including significant cardiovascular disease, diabetes,&#xD;
             chronic renal disease, chronic thyroid disease, history of chronic infections or&#xD;
             immunodeficiency.&#xD;
&#xD;
          -  Physician directed emergency treatment for an asthma exacerbation within the preceding&#xD;
             12 months.&#xD;
&#xD;
          -  Exacerbation of asthma more than 2x/week which could be characteristic of a person of&#xD;
             moderate or severe persistent asthma as outlined in the current NHLBI guidelines for&#xD;
             diagnosis and management of asthma.&#xD;
&#xD;
          -  Daily requirements 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;
          -  Viral upper respiratory tract infection within 4 weeks of challenge.&#xD;
&#xD;
          -  Any acute infection requiring antibiotics within 6 weeks of exposure or fever of&#xD;
             unknown origin within 6 weeks of challenge.&#xD;
&#xD;
          -  Severe asthma&#xD;
&#xD;
          -  Mental illness or history of drug or alcohol abuse that, in the opinion of the&#xD;
             investigator, would interfere with the participant's ability to comply with study&#xD;
             requirements.&#xD;
&#xD;
          -  Cigarette smoking &gt;1 pack per month&#xD;
&#xD;
          -  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;
          -  Allergy/sensitivity to study drugs or their formulations&#xD;
&#xD;
          -  Known hypersensitivity to methacholine or to other parasympathomimetic agents&#xD;
&#xD;
          -  History of intubation for asthma&#xD;
&#xD;
          -  Unwillingness to avoid coffee, tea, cola drinks, chocolate, or other foods containing&#xD;
             caffeine after midnight on the days that methacholine challenge testing is to be&#xD;
             performed.&#xD;
&#xD;
          -  Unwillingness to use reliable contraception if sexually active (IUD, birth control&#xD;
             pills/patch, condoms).&#xD;
&#xD;
          -  Pregnancy or nursing a baby. Female volunteers will be asked to use effective birth&#xD;
             control (stable regimen of hormonal contraceptive use for at least 3 months,&#xD;
             intrauterine device placement, tubal ligation or endometrial ablation for at least 3&#xD;
             months through at least one week after study completion) and will provide a urine&#xD;
             sample to test for pregnancy on study days. If the test is positive or the subject has&#xD;
             reason to believe she may be pregnant, she will be dismissed from the study. Women who&#xD;
             have been amenorrheic for 12 months may participate. Male volunteers will be asked to&#xD;
             use condoms for the duration of the study through at least one week after study&#xD;
             completion.&#xD;
&#xD;
        Usage of the following medications:&#xD;
&#xD;
          -  Use of systemic steroid therapy within the preceding 12 months for an asthma&#xD;
             exacerbation. All use of systemic steroids in the last year will be reviewed by a&#xD;
             study physician.&#xD;
&#xD;
          -  Subjects who are prescribed daily inhaled corticosteroids, cromolyn, or leukotriene&#xD;
             inhibitors (Montelukast or Zafirlukast) will be required to discontinue these&#xD;
             medications at least 2 weeks prior to their screening visit.&#xD;
&#xD;
          -  Use of daily theophylline within the past month.&#xD;
&#xD;
          -  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;
          -  Use of any immunosuppressant therapy within the preceding 12 months will be reviewed&#xD;
             by the study physician.&#xD;
&#xD;
          -  Receipt of Live Attenuated Influenza Vaccine (LAIV), also known as FluMist®, or any&#xD;
             other live viral vaccine within the prior 30 days, or any vaccine for at least 5 days&#xD;
&#xD;
          -  Use of beta blocking medications&#xD;
&#xD;
          -  Antihistamines in the 5 days prior to allergen challenge&#xD;
&#xD;
          -  Routine use of NSAIDs, including aspirin.&#xD;
&#xD;
        Physical/laboratory indications:&#xD;
&#xD;
          -  Abnormalities on lung auscultation&#xD;
&#xD;
          -  Temperature &gt;37.8°C&#xD;
&#xD;
          -  Oxygen saturation of &lt;94%&#xD;
&#xD;
          -  Systolic BP&gt;150 mmHg or &lt;90 mmHg or diastolic BP&gt;90 mmHg or &lt;60 mmHg&#xD;
&#xD;
          -  Inability or unwillingness of a participant to give written informed consent&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Michelle Hernandez, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of North Carolina, Chapel Hill</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Katie Mills</name>
      <address>
        <city>Chapel Hill</city>
        <state>North Carolina</state>
        <zip>27599</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2022</verification_date>
  <study_first_submitted>December 17, 2018</study_first_submitted>
  <study_first_submitted_qc>December 17, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 19, 2018</study_first_posted>
  <results_first_submitted>June 16, 2022</results_first_submitted>
  <results_first_submitted_qc>June 16, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">July 14, 2022</results_first_posted>
  <last_update_submitted>September 22, 2022</last_update_submitted>
  <last_update_submitted_qc>September 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 18, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Felis Catus (cat)</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Respiratory Aspiration</mesh_term>
    <mesh_term>Asthma</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Yes</sharing_ipd>
    <ipd_description>Individual participant data that underlie the results reported in this article, after deidentification (text, tables, ﬁgures, and appendices).</ipd_description>
    <ipd_info_type>Study Protocol</ipd_info_type>
    <ipd_time_frame>Beginning 9 months and ending 36 months following article publication</ipd_time_frame>
    <ipd_access_criteria>Investigators whose proposed use of the data has been approved by an independent review committee (&quot;learned intermediary&quot;) identified for this purpose.&#xD;
Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata&#xD;
Requests for access to individual participant data should be sent to bring44@email.unc.edu or carole.robinette@med.unc.edu. Access will be granted after a data access agreement has been signed with the University of North Carolina (UNC)</ipd_access_criteria>
  </patient_data>
  <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>May 13, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/87/NCT03780387/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Inhaled Allergen Challenge</title>
          <description>Inhalation of Felis Catus allergen in participants with documented allergic sensitization to cat hair.&#xD;
Control diluent followed by concentrations of Felis Catus allergen administered at 10-minute intervals starting with solutions of 0.31, 0.61, 1.22, 2.44, 4.89, 9.77, 19.5, 39, 78.13, 156.25, 312.5, and 625 BAU/mL via nebulizer until an FEV1 decline &gt;/= 20% reached.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Inhaled Allergen Challenge</title>
          <description>Felis Catus sensitive, mild asthmatics will undergo inhaled allergen challenge.&#xD;
Felis Catus: Inhalation of Felis Catus allergen in subjects allergic to Felis Catus</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="1"/>
          </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_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" 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="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Maximum Change in the Percentage of Forced Expiratory Volume in 1 Second (FEV1)</title>
        <description>Pre-challenge FEV1 is measured just prior to administration of the allergen challenge. FEV1 is measured at regular intervals for 10 hours after the challenge. [(Lowest FEV1 value post-challenge - Pre-challenge FEV1 value)/(Pre-challenge FEV1 value)]*100</description>
        <time_frame>Pre-challenge to 10 hours post-challenge</time_frame>
        <population>A single participant completed the cat allergen inhalation challenge.</population>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Allergen Challenge</title>
            <description>Inhalation of cat hair allergen in participants with documented allergic sensitization to cat hair</description>
          </group>
        </group_list>
        <measure>
          <title>Maximum Change in the Percentage of Forced Expiratory Volume in 1 Second (FEV1)</title>
          <description>Pre-challenge FEV1 is measured just prior to administration of the allergen challenge. FEV1 is measured at regular intervals for 10 hours after the challenge. [(Lowest FEV1 value post-challenge - Pre-challenge FEV1 value)/(Pre-challenge FEV1 value)]*100</description>
          <population>A single participant completed the cat allergen inhalation challenge.</population>
          <units>percentage change in FEV1</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-21" spread="NA">Standard deviation (SD) not calculated for 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Levels of IL-1β in Induced Sputum</title>
        <description>Participants will undergo a hypertonic saline induced sputum procedure at baseline (within ~2 weeks of the allergen challenge), and again at 24 hours following inhaled allergen challenge. IL-1β concentrations in the sputum will be determined via ELISA. In addition to assessing changes in IL-1β levels, we will determine if IL-1β levels are predictive of key asthma outcomes following inhaled allergen challenge (see outcomes 3-7).</description>
        <time_frame>Baseline and 24 hours post- inhalation challenge</time_frame>
        <population>Samples are typically batch processed and it was cost-prohibitive to run one participant's sample.</population>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Allergen Challenge</title>
            <description>Inhalation of cat hair allergen in participants with documented allergic sensitization to cat hair</description>
          </group>
        </group_list>
        <measure>
          <title>Levels of IL-1β in Induced Sputum</title>
          <description>Participants will undergo a hypertonic saline induced sputum procedure at baseline (within ~2 weeks of the allergen challenge), and again at 24 hours following inhaled allergen challenge. IL-1β concentrations in the sputum will be determined via ELISA. In addition to assessing changes in IL-1β levels, we will determine if IL-1β levels are predictive of key asthma outcomes following inhaled allergen challenge (see outcomes 3-7).</description>
          <population>Samples are typically batch processed and it was cost-prohibitive to run one participant's sample.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in the Percentage of Sputum Eosinophils</title>
        <description>Induced sputum obtained pre-challenge and again at 24 hours post-challenge will be assessed for cells. (% eosinophils post-challenge - %eosinophils pre-challenge)</description>
        <time_frame>Pre-challenge and 24 hours post-challenge</time_frame>
        <population>a single participant underwent inhaled cat allergen challenge.</population>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Allergen Challenge</title>
            <description>Inhalation of cat hair allergen in participants with documented allergic sensitization to cat hair</description>
          </group>
        </group_list>
        <measure>
          <title>Change in the Percentage of Sputum Eosinophils</title>
          <description>Induced sputum obtained pre-challenge and again at 24 hours post-challenge will be assessed for cells. (% eosinophils post-challenge - %eosinophils pre-challenge)</description>
          <population>a single participant underwent inhaled cat allergen challenge.</population>
          <units>percentage of eosinophils</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.16" spread="NA">SD not calculated for 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mucins in Sputum</title>
        <description>Sputum mucins will be measured at baseline, and again at 24 hours following inhaled allergen challenge</description>
        <time_frame>Baseline and 24 hours post- inhalation challenge</time_frame>
        <population>Samples are typically batch processed and it was cost-prohibitive to run one participant's sample.</population>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Allergen Challenge</title>
            <description>Inhalation of cat hair allergen in participants with documented allergic sensitization to cat hair</description>
          </group>
        </group_list>
        <measure>
          <title>Mucins in Sputum</title>
          <description>Sputum mucins will be measured at baseline, and again at 24 hours following inhaled allergen challenge</description>
          <population>Samples are typically batch processed and it was cost-prohibitive to run one participant's sample.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants Who Experience a Late Phase Response (Fall in FEV1≥15%) to Inhaled Allergen</title>
        <description>FEV1 will be measured prior to administration of the inhaled allergen challenge. The maximum drop in FEV1 that occurs during the late phase (3-10 hours after challenge) will be determined.</description>
        <time_frame>Pre-challenge to 10 hours post-challenge</time_frame>
        <population>A single participant underwent inhaled challenge with cat hair allergen</population>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Allergen Challenge</title>
            <description>Inhalation of cat hair allergen in participants with documented allergic sensitization to cat hair</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants Who Experience a Late Phase Response (Fall in FEV1≥15%) to Inhaled Allergen</title>
          <description>FEV1 will be measured prior to administration of the inhaled allergen challenge. The maximum drop in FEV1 that occurs during the late phase (3-10 hours after challenge) will be determined.</description>
          <population>A single participant underwent inhaled challenge with cat hair allergen</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Airway Hyperresponsiveness Measured by Difference in Methacholine Dose Required to Produce a ≥20% Fall in FEV1 (PC20)</title>
        <description>Participants will undergo a methacholine challenge to assess airway hyper-responsiveness at baseline. Changes in methacholine reactivity from baseline to 24 hours post-allergen challenge will be determined. Negative values indicate decrease and positive values indicate increase in doubling. (methacholine PC20 post-challenge - methacholine PC20 pre-challenge).</description>
        <time_frame>Baseline to 24 hours post-challenge</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Allergen Challenge</title>
            <description>Inhalation of cat hair allergen in participants with documented allergic sensitization to cat hair</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Airway Hyperresponsiveness Measured by Difference in Methacholine Dose Required to Produce a ≥20% Fall in FEV1 (PC20)</title>
          <description>Participants will undergo a methacholine challenge to assess airway hyper-responsiveness at baseline. Changes in methacholine reactivity from baseline to 24 hours post-allergen challenge will be determined. Negative values indicate decrease and positive values indicate increase in doubling. (methacholine PC20 post-challenge - methacholine PC20 pre-challenge).</description>
          <units>mg/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="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.5" spread="NA">SD not calculated for 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Exhaled Nitric Oxide (eNO) Levels in Ppb</title>
        <description>eNO levels will be measured pre-challenge, and 24 hours post-challenge. (eNO value post-challenge - eNO value pre-challenge)</description>
        <time_frame>Pre-challenge to 24 hours post-challenge</time_frame>
        <population>A single participant underwent inhalation challenge with cat hair allergen.</population>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Allergen Challenge</title>
            <description>Inhalation of cat hair allergen in participants with documented allergic sensitization to cat hair</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Exhaled Nitric Oxide (eNO) Levels in Ppb</title>
          <description>eNO levels will be measured pre-challenge, and 24 hours post-challenge. (eNO value post-challenge - eNO value pre-challenge)</description>
          <population>A single participant underwent inhalation challenge with cat hair allergen.</population>
          <units>parts per billion</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-4" spread="NA">SD not calculated for 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Heart Rate Variability (HRV)</title>
        <description>HRV with Spacelabs technology will be measured 24 hours pre and during inhalation challenge</description>
        <time_frame>Pre challenge and immediately post challenge</time_frame>
        <population>Monitoring equipment were unavailable after being lost during transit and these data were not collected.</population>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Allergen Challenge</title>
            <description>Inhalation of cat hair allergen in participants with documented allergic sensitization to cat hair</description>
          </group>
        </group_list>
        <measure>
          <title>Heart Rate Variability (HRV)</title>
          <description>HRV with Spacelabs technology will be measured 24 hours pre and during inhalation challenge</description>
          <population>Monitoring equipment were unavailable after being lost during transit and these data were not collected.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Concentration of Inflammatory Cytokines in Nasal Epithelial Lining Fluid</title>
        <description>Nasal fluid collected for analysis of cytokines IL-8, IL-6, IL-1alpha, IL-1 beta. [(Cytokine concentration immediately post-challenge) - (cytokine concentration pre-challenge)].</description>
        <time_frame>Pre challenge and immediately post challenge</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Allergen Challenge</title>
            <description>Inhalation of cat hair allergen in participants with documented allergic sensitization to cat hair</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Concentration of Inflammatory Cytokines in Nasal Epithelial Lining Fluid</title>
          <description>Nasal fluid collected for analysis of cytokines IL-8, IL-6, IL-1alpha, IL-1 beta. [(Cytokine concentration immediately post-challenge) - (cytokine concentration pre-challenge)].</description>
          <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="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>IL-8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-14790.89" spread="NA">SD not calculated for 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-11.54" spread="NA">SD not calculated for 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-1alpha</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="22.12" spread="NA">SD not calculated for 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-1 beta</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-23.71" spread="NA">SD not calculated for 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Concentration of Inflammatory Cytokines in Nasal Epithelial Lining Fluid</title>
        <description>Nasal strip to collect cytokines IL-8, IL-6, IL-1alpha, IL-1 beta. [(Cytokine concentration 7h post-challenge) - (cytokine concentration pre-challenge)].</description>
        <time_frame>Pre challenge and 7 hours post challenge</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Allergen Challenge</title>
            <description>Inhalation of cat hair allergen in participants with documented allergic sensitization to cat hair</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Concentration of Inflammatory Cytokines in Nasal Epithelial Lining Fluid</title>
          <description>Nasal strip to collect cytokines IL-8, IL-6, IL-1alpha, IL-1 beta. [(Cytokine concentration 7h post-challenge) - (cytokine concentration pre-challenge)].</description>
          <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="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>IL-8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-16076.98" spread="NA">SD not calculated for 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-21.78" spread="NA">SD not calculated for 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-1a</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="24.52" spread="NA">SD not calculated for 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-1b</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.74" spread="NA">SD not calculated for 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Concentration of Inflammatory Cytokines in Nasal Epithelial Lining Fluid</title>
        <description>Nasal strip to collect cytokine IL-8, IL-6, IL-1alpha, IL-1 beta. [(Cytokine concentration 24h post-challenge) - (cytokine concentration pre-challenge)].</description>
        <time_frame>Pre challenge and 24 hours post challenge</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Inhaled Allergen Challenge</title>
            <description>Inhalation of cat hair allergen in participants with documented allergic sensitization to cat hair</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Concentration of Inflammatory Cytokines in Nasal Epithelial Lining Fluid</title>
          <description>Nasal strip to collect cytokine IL-8, IL-6, IL-1alpha, IL-1 beta. [(Cytokine concentration 24h post-challenge) - (cytokine concentration pre-challenge)].</description>
          <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="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>IL-8</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-10763.58" spread="NA">SD not calculated for 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.09" spread="NA">SD not calculated for 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-1a</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="70.14" spread="NA">SD not calculated for 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>IL-1b</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-21.21" spread="NA">SD not calculated for 1 participant.</measurement>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data were collected from the time written informed consent was obtained until 10 days after the inhaled allergen challenge.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Inhaled Allergen Challenge</title>
          <description>Felis Catus sensitive, mild asthmatics will undergo inhaled allergen challenge.&#xD;
Felis Catus: Inhalation of Felis Catus allergen in subjects allergic to Felis Catus</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="1"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="1"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" 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>Michelle Hernandez, MD</name_or_title>
      <organization>University of North Carolina at Chapel Hill</organization>
      <phone>919-843-5383</phone>
      <email>michelle_hernandez@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/NCT03780387
org study id: 18-2006
secondary id: 1R01HL135235-01A1
nct id: NCT03780387
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
This study is designed to identify Felis Catus, or cat hair, sensitive asthmatics who
      demonstrate a late phase asthmatic response after cat hair inhalation. These subjects may be
      invited to participate in a planned future study investigating novel asthma treatments.
Asthma is an increasingly common chronic illness among children and adults, and allergen
      exposure is among the most common triggers for asthma exacerbations. Exacerbations of
      allergic asthma are characterized by an early phase response (EPR), mediated by release of
      preformed mediators like histamine from mast cells, and a late phase response (LPR) 3-7 hours
      later mediated by chemokines and cytokines that attract leukocytes such as neutrophils and
      eosinophils to the airways, increase mucus production, trigger airway smooth muscle
      contraction, and result in airway constriction and airway hyperreactivity (AHR). The LPR does
      not occur in the absence of an EPR. The LPR is thought to be predominantly responsible for
      the symptoms associated with acute exacerbations of allergic asthma and is often used as the
      measure of efficacy in trials of asthma therapeutics.

      This group has taken a particular interest in targeting an inflammatory cytokine,
      Interleukin-1β, involved in both the early and late phase asthmatic responses to inhaled
      allergen in allergic asthmatics. In the lung, interleukin 1 beta (IL-1β) is produced by
      numerous cell types (including epithelial cells, macrophages, neutrophils, eosinophils, and
      mast cells), where it signals through its receptor to induce transcription of
      pro-inflammatory genes (17-19). IL-1β is increased in bronchoalveolar lavage fluid from
      persons with symptomatic asthma vs. those with asymptomatic asthma; likewise,
      immunohistochemistry of bronchial biopsies of allergic asthmatics reveal increased expression
      of IL-1β in both bronchial epithelial cells and macrophages.

      In order to better understand the role of IL-1β in allergen-induced airway inflammation,
      induced sputum will be obtained to determine if higher baseline sputum IL-1β concentrations
      or larger increases in IL-1β following allergen challenge impact non-specific airway
      hyperresponsiveness (via methacholine challenge), sputum granulocyte recruitment (neutrophil
      and eosinophil counts and exhaled nitric oxide (eNO), a marker of airway eosinophilia), or
      changes in expression of inflammatory or allergy-related genes. To this last point, little is
      known about the mechanisms contributing to response patterns in allergic asthmatics
      undergoing allergen challenge. Changes in gene expression occurring during the window of time
      between the EPR and LPR, as these expression changes may dictate whether or not a LPR occurs
      or to what extent it occurs.

      The goal of this screening protocol is to identify subjects who exhibit both an EPR and LPR
      and who will be eligible for enrollment in the yet to be developed IL-1β protocols. Subjects
      will undergo a baseline methacholine challenge to establish reactivity, then allergen
      exposure, followed 24 hours later by methacholine challenge.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Maximum Change in the Percentage of Forced Expiratory Volume in 1 Second (FEV1)
time frame: Pre-challenge to 10 hours post-challenge
description: Pre-challenge FEV1 is measured just prior to administration of the allergen challenge. FEV1 is measured at regular intervals for 10 hours after the challenge. [(Lowest FEV1 value post-challenge - Pre-challenge FEV1 value)/(Pre-challenge FEV1 value)]*100
measure: Levels of IL-1β in Induced Sputum
time frame: Baseline and 24 hours post- inhalation challenge
description: Participants will undergo a hypertonic saline induced sputum procedure at baseline (within ~2 weeks of the allergen challenge), and again at 24 hours following inhaled allergen challenge. IL-1β concentrations in the sputum will be determined via ELISA. In addition to assessing changes in IL-1β levels, we will determine if IL-1β levels are predictive of key asthma outcomes following inhaled allergen challenge (see outcomes 3-7).
measure: Change in the Percentage of Sputum Eosinophils
time frame: Pre-challenge and 24 hours post-challenge
description: Induced sputum obtained pre-challenge and again at 24 hours post-challenge will be assessed for cells. (% eosinophils post-challenge - %eosinophils pre-challenge)
measure: Mucins in Sputum
time frame: Baseline and 24 hours post- inhalation challenge
description: Sputum mucins will be measured at baseline, and again at 24 hours following inhaled allergen challenge
measure: Number of Participants Who Experience a Late Phase Response (Fall in FEV1≥15%) to Inhaled Allergen
time frame: Pre-challenge to 10 hours post-challenge
description: FEV1 will be measured prior to administration of the inhaled allergen challenge. The maximum drop in FEV1 that occurs during the late phase (3-10 hours after challenge) will be determined.
measure: Change in Airway Hyperresponsiveness Measured by Difference in Methacholine Dose Required to Produce a ≥20% Fall in FEV1 (PC20)
time frame: Baseline to 24 hours post-challenge
description: Participants will undergo a methacholine challenge to assess airway hyper-responsiveness at baseline. Changes in methacholine reactivity from baseline to 24 hours post-allergen challenge will be determined. Negative values indicate decrease and positive values indicate increase in doubling. (methacholine PC20 post-challenge - methacholine PC20 pre-challenge).
measure: Change in Exhaled Nitric Oxide (eNO) Levels in Ppb
time frame: Pre-challenge to 24 hours post-challenge
description: eNO levels will be measured pre-challenge, and 24 hours post-challenge. (eNO value post-challenge - eNO value pre-challenge)
measure: Heart Rate Variability (HRV)
time frame: Pre challenge and immediately post challenge
description: HRV with Spacelabs technology will be measured 24 hours pre and during inhalation challenge
measure: Change in Concentration of Inflammatory Cytokines in Nasal Epithelial Lining Fluid
time frame: Pre challenge and immediately post challenge
description: Nasal fluid collected for analysis of cytokines IL-8, IL-6, IL-1alpha, IL-1 beta. [(Cytokine concentration immediately post-challenge) - (cytokine concentration pre-challenge)].
measure: Change in Concentration of Inflammatory Cytokines in Nasal Epithelial Lining Fluid
time frame: Pre challenge and 7 hours post challenge
description: Nasal strip to collect cytokines IL-8, IL-6, IL-1alpha, IL-1 beta. [(Cytokine concentration 7h post-challenge) - (cytokine concentration pre-challenge)].
measure: Change in Concentration of Inflammatory Cytokines in Nasal Epithelial Lining Fluid
time frame: Pre challenge and 24 hours post challenge
description: Nasal strip to collect cytokine IL-8, IL-6, IL-1alpha, IL-1 beta. [(Cytokine concentration 24h post-challenge) - (cytokine concentration pre-challenge)].
arm group label: Inhaled Allergen Challenge
arm group type: Experimental
description: Felis Catus sensitive, mild asthmatics will undergo inhaled allergen challenge.
intervention type: Biological
intervention name: Felis Catus
description: Inhalation of Felis Catus allergen in subjects allergic to Felis Catus
arm group label: Inhaled Allergen Challenge
other name: Cat hair
other name: Cat
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Michelle Hernandez, MD
role: Principal Investigator
affiliation: University of North Carolina, Chapel Hill
facility: 
country: United States
responsible party type: Sponsor
mesh term: Respiratory Aspiration
mesh term: Asthma
sharing ipd: Yes
ipd description: Individual participant data that underlie the results reported in this article, after deidentification (text, tables, ﬁgures, and appendices).
ipd info type: Study Protocol
ipd time frame: Beginning 9 months and ending 36 months following article publication
ipd access criteria: Investigators whose proposed use of the data has been approved by an independent review committee ("learned intermediary") identified for this purpose.
Proposals may be submitted up to 36 months following article publication. After 36 months the data will be available in our University's data warehouse but without investigator support other than deposited metadata
Requests for access to individual participant data should be sent to bring44@email.unc.edu or carole.robinette@med.unc.edu. Access will be granted after a data access agreement has been signed with the University of North Carolina (UNC)
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 