<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/NCT03031145</url>
  </required_header>
  <id_info>
    <org_study_id>16-1686</org_study_id>
    <nct_id>NCT03031145</nct_id>
  </id_info>
  <brief_title>Investigation of the Impact of Smoking Status on Allergen-induced Nasal Airway Inflammation Using a Cat Hair (Felis Domesticus) Extract Nasal Allergen Challenge Model</brief_title>
  <acronym>Kitty Nose</acronym>
  <official_title>Investigation of the Impact of Smoking Status on Allergen-induced Nasal Airway Inflammation Using a Cat Hair (Felis Domesticus) Extract Nasal Allergen Challenge Model</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 felis domesticus, or cat, extract in e-cigarette users,&#xD;
      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 let to safety concerns regarding their potential role in&#xD;
      respiratory disease. These tobacco alternatives 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 that while they contain fewer toxins and carcinogens than conventional&#xD;
      cigarettes, they do involve delivery of ultrafine particles to the lower airways and can&#xD;
      contain heavy metals and other chemicals. Tobacco Smoke may augment allergic inflammation&#xD;
      resulting from allergic rhinitis and/or asthma. Animal models of allergic asthma demonstrate&#xD;
      aggravation of allergen -induced airway inflammation following inhalation of e-cig cartridge&#xD;
      solution, with increased airway eosinophil infiltration, production of Th2 cytokines, and&#xD;
      airway hyperresponsivness. In vitro studies in human tissues have demonstrated&#xD;
      pro-inflammatory responses in a similar way as tobacco smoke, yet a head-to-head comparison&#xD;
      of the effects of these two exposures has not been performed in 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 o f this study is to&#xD;
      study the impact of these products on allergic inflammation in cat allergic subjects who&#xD;
      already routinely use e-cigarettes and to compare their response to those of cigarette&#xD;
      smokers and non-smokers. A thorough understanding of the potential health impacts of tobacco&#xD;
      alternative substances in seeded, especially given the rising popularity of such products&#xD;
      with adolescents and young adults to whom these substances have particular appeals given the&#xD;
      purported safety: and variety of flavors to chose from.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Lack of funding&#xD;
  </why_stopped>
  <start_date type="Actual">April 3, 2017</start_date>
  <completion_date type="Actual">December 4, 2017</completion_date>
  <primary_completion_date type="Actual">December 4, 2017</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>Change in eosinophils/mL in nasal lavage fluid (NLF)</measure>
    <time_frame>Pre- and 4 hours post- nasal allergen challenge</time_frame>
    <description>NLF will be collected immediately prior to administration of the nasal allergen challenge. 4 hours after administration of a bolus provocative dose of allergen (determined at screening day visit nasal allergen challenge), NLF will be collected. Pre- and 4 hours post-challenge NLF will be analyzed for cellularity. Values will be compared across e-cigarette smokers, tobacco cigarette smokers, and non-smokers.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Nasal lavage fluid cytokines</measure>
    <time_frame>Pre- and 4 hours post- nasal allergen challenge</time_frame>
    <description>NLF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post-nasal allergen challenge. Cytokine levels will be quantified with commercially available ELISAs.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Nasal epithelial cell messenger ribonucleic acid (mRNA)</measure>
    <time_frame>Baseline (within two months of nasal allergen challenge) and 4 hours post- nasal allergen challenge</time_frame>
    <description>Nasal epithelial cell biopsies will be collected at baseline (within two months of nasal allergen challenge), and 4 hours post-nasal allergen challenge. Gene expression changes will be quantified using qRT-PCR.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Tobacco Smoking</condition>
  <condition>Healthy Participants</condition>
  <condition>E-cigarette Smokers</condition>
  <arm_group>
    <arm_group_label>Felis Domesticus treated Non-smoker</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Felis Domesticus treated E-cigarette smoker</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Felis Domesticus treated Cigarette smoker</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Biological</intervention_type>
    <intervention_name>Felis Domesticus</intervention_name>
    <description>Nasal Administration of Felis Domesticus</description>
    <arm_group_label>Felis Domesticus treated Cigarette smoker</arm_group_label>
    <arm_group_label>Felis Domesticus treated E-cigarette smoker</arm_group_label>
    <arm_group_label>Felis Domesticus treated Non-smoker</arm_group_label>
    <other_name>Cat Allergen</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Males and females age 18-50 years&#xD;
&#xD;
          2. Specific allergy to cat hair Felis domesticus confirmed by positive immediate skin&#xD;
             test response&#xD;
&#xD;
          3. Subjects may be enrolled with mild asthma if a Forced Expiratory Volume in 1 second&#xD;
             (FEV1) of at least 80% of predicted and a Forced Expiratory Volume in 1 second to&#xD;
             Forced Vital Capacity (FVC) ratio (FEV1/FVC ratio) of at least .75 (without use of&#xD;
             bronchodilator medications for 12 hours), consistent with lung function of persons&#xD;
             with mild episodic or mild persistent asthma is demonstrated. For the purpose of this&#xD;
             protocol, an asthmatic individual will be defined as having a) positive methacholine&#xD;
             challenge with a provocative concentration of methacholine producing a 20% fall in&#xD;
             FEV1 (PC20 methacholine) with less than or equal to 10 mg/ml; OR b) physician&#xD;
             diagnosed asthma with symptoms and chronic daily therapy consistent with the mild&#xD;
             asthma&#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;
          6. Subjects will be classified as tobacco smokers, e-cigarette users, or non-smokers&#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 Zafirkulast) within the past month (except for use of cromolyn&#xD;
             exclusively prior to exercise).&#xD;
&#xD;
          5. Use of allergen immunotherapy.&#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, IUD, estrogen patches) or who are not completely 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 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 investigational agent within the last 30 days.&#xD;
&#xD;
         17. Use of tricyclic antidepressants or beta-blockers.&#xD;
&#xD;
         18. Use of MAO inhibitors or any medications known to interfere with the treatment of&#xD;
             anaphylaxis.&#xD;
&#xD;
         19. Subjects with a history of immunologic disease or undergoing immune suppression for&#xD;
             cancer or other diseases.&#xD;
&#xD;
         20. Subjects with acute inflammatory conditions in the nose or paranasal sinuses, such as&#xD;
             sinusitis.&#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 21, 2017</study_first_submitted>
  <study_first_submitted_qc>January 21, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 25, 2017</study_first_posted>
  <last_update_submitted>May 5, 2021</last_update_submitted>
  <last_update_submitted_qc>May 5, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 7, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Inflammation</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03031145
org study id: 16-1686
nct id: NCT03031145
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 felis domesticus, or cat, 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 let to safety concerns regarding their potential role in
      respiratory disease. These tobacco alternatives devices were initially perceived as a "safer"
      alternative to cigarettes and were marketed without much known about their health effects.
      Increasing evidence 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 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 o f this study is to
      study the impact of these products on allergic inflammation in cat allergic subjects who
      already routinely use e-cigarettes and to compare their response to those of cigarette
      smokers and non-smokers. A thorough understanding of the potential health impacts of tobacco
      alternative substances in seeded, especially given the rising popularity of such products
      with adolescents and young adults to whom these substances have particular appeals given the
      purported safety: and variety of flavors to chose from.
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Change in eosinophils/mL in nasal lavage fluid (NLF)
time frame: Pre- and 4 hours post- nasal allergen challenge
description: NLF will be collected immediately prior to administration of the nasal allergen challenge. 4 hours after administration of a bolus provocative dose of allergen (determined at screening day visit nasal allergen challenge), NLF will be collected. Pre- and 4 hours post-challenge NLF will be analyzed for cellularity. Values will be compared across e-cigarette smokers, tobacco cigarette smokers, and non-smokers.
measure: Nasal lavage fluid cytokines
time frame: Pre- and 4 hours post- nasal allergen challenge
description: NLF will be collected immediately prior to administration of the nasal allergen challenge, and 4 hours post-nasal allergen challenge. Cytokine levels will be quantified with commercially available ELISAs.
measure: Nasal epithelial cell messenger ribonucleic acid (mRNA)
time frame: Baseline (within two months of nasal allergen challenge) and 4 hours post- nasal allergen challenge
description: Nasal epithelial cell biopsies will be collected at baseline (within two months of nasal allergen challenge), and 4 hours post-nasal allergen challenge. Gene expression changes will be quantified using qRT-PCR.
arm group label: Felis Domesticus treated Non-smoker
arm group type: Active Comparator
arm group label: Felis Domesticus treated E-cigarette smoker
arm group type: Active Comparator
arm group label: Felis Domesticus treated Cigarette smoker
arm group type: Active Comparator
intervention type: Biological
intervention name: Felis Domesticus
description: Nasal Administration of Felis Domesticus
arm group label: Felis Domesticus treated Cigarette smoker
arm group label: Felis Domesticus treated E-cigarette smoker
arm group label: Felis Domesticus treated Non-smoker
other name: Cat Allergen
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
sharing ipd: No