<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/NCT02188511</url>
  </required_header>
  <id_info>
    <org_study_id>1312014623</org_study_id>
    <nct_id>NCT02188511</nct_id>
  </id_info>
  <brief_title>Effects of Electronic Cigarettes on Lung Biology</brief_title>
  <official_title>Effects of Electronic Cigarettes on Lung Biology</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Weill Medical College of Cornell University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Weill Medical College of Cornell University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      E-cigarettes are an increasingly popular alternate nicotine delivery system, but nothing is&#xD;
      known about the effects of electronic cigarettes on the lungs. We hypothesize that&#xD;
      e-cigarettes disorder airway epithelial and alveolar macrophages biology. Our goal is not to&#xD;
      carry out a large epidemiologic study of electronic cigarette users to study lung function&#xD;
      and other possible abnormal clinical phenotypes, but rather to focus on whether electronic&#xD;
      cigarette smoke disorders the biology of the lung cells first exposed to the electronic&#xD;
      cigarette smoke, a parameter that is the precursor of abnormalities in lung function and&#xD;
      which is far more sensitive than lung function.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The specific aim of this study is to assess the hypothesis that electronic smoking disorders&#xD;
      the biology of the airway epithelium and alveolar macrophages, to evaluate these changes in&#xD;
      the lungs of normal nonsmokers exposed to electronic cigarettes, and to directly determine if&#xD;
      the inhaled smoke from electronic cigarettes disturbs the biology of the naïve lung that has&#xD;
      not been exposed to tobacco products. Because nicotine can be addictive with continual use,&#xD;
      we will limit the exposure to a maximum of a nicotine equivalent of 1/2 pack of cigarettes&#xD;
      over a 5 day period, a level that has been used safely in studies of healthy nonsmokers'&#xD;
      naïve to nicotine.&#xD;
&#xD;
      To obtain the most unbiased data about the effect of electronic cigarette use on the lung,&#xD;
      normal nonsmokers will be briefly exposed to electronic cigarettes and lung cells, airway&#xD;
      epithelium and alveolar macrophages, lung epithelial lining fluid (ELF) and serum will be&#xD;
      collected before and after e-cigarette exposure. There will be 5 study groups consisting of&#xD;
      10 non-smoker subjects (A-E), with each group undergoing an increased exposure to the amount&#xD;
      of e-cigarettes (Group a being the lowest exposure, group E being the highest). Six of the&#xD;
      subjects in each group will be exposed to e-cigarettes with nicotine while the remaining four&#xD;
      in each group being exposed to nicotine-free e-cigarettes. Subjects will be assigned to use&#xD;
      electronic cigarettes that either do or do not contain nicotine in a randomized, blinded&#xD;
      manner.&#xD;
&#xD;
      The duration of which the subjects will be observed for e-cigarette exposure will be 8 days.&#xD;
      Baselines for each group will be established on Day 1 in which all subjects will undergo a&#xD;
      bronchoscopy and an assessment of vital signs.&#xD;
&#xD;
      For subjects in group A, at the day 8 visit after the vital signs are assessed, 3 hours prior&#xD;
      to bronchoscopy, the subject will be asked to inhale 10 puffs of a &quot;Blu&quot; brand e-cigarette&#xD;
      (for the nicotine-containing e-cigarette, this is approximately equivalent to &lt; 1 cigarette).&#xD;
      At 2 hours prior to the bronchoscopy procedure, if the subject has no adverse effect to the&#xD;
      e-cigarette he/she will again be asked to inhale 10 puffs of the &quot;Blu&quot; e-cigarette. The vital&#xD;
      signs will again be confirmed and any symptoms assessed prior to proceeding with&#xD;
      bronchoscopy. Subjects in group B will undergo an identical exposure, but on both days 7 and&#xD;
      8. Subjects in group C will undergo similar exposure on days 6-8, group D on days 5-8, and&#xD;
      group E days 4-8 for a maximum of 5 exposure days prior to bronchoscopy. The research team&#xD;
      will contact subjects at 1 month and 6 months after their Day 8 bronchoscopy in order to&#xD;
      determine whether or not they have become dependent on nicotine.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Lack of funding&#xD;
  </why_stopped>
  <start_date type="Actual">January 2014</start_date>
  <completion_date type="Actual">July 2018</completion_date>
  <primary_completion_date type="Actual">July 2018</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Airway epithelium and aveolar macrophage</measure>
    <time_frame>8 days</time_frame>
    <description>Changes in airway epithelium and aveolar macrophage will be measured by bronchoscopy</description>
  </primary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">13</enrollment>
  <condition>Lung Disease</condition>
  <condition>Lung Disorder</condition>
  <arm_group>
    <arm_group_label>Group A</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Electronic cigarette (nicotine/placebo) - Day 8 Intervention: Electronic cigarette exposure will be limited to one day.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group B</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Electronic cigarette (nicotine/placebo) - Days 7 through 8 Electronic cigarette exposure will be limited to two days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group C</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Electronic cigarette (nicotine/placebo) - Days 6 through 8 Electronic cigarette exposure will be limited to 3 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group D</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Electronic cigarette (nicotine/placebo) - Days 5 through 8 Electronic cigarette exposure will be limited to 4 days</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Group E</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Electronic cigarette (nicotine/placebo) - Days 4 through 8 Electronic cigarette exposure will be limited to 5 days.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Group A</intervention_name>
    <description>90 minutes prior to the bronchoscopy on day 8, the subject will be asked to inhale 10 puffs of a Blu brand e-cigarette (for the nicotine-containing e-cigarette, this is approximately equivalent to &lt; 1 cigarette). At 30 minutes prior to the bronchoscopy procedure if the subject has no adverse effect to the e-cigarette he/she will again be asked to inhale 10 puffs of the Blu e-cigarette.</description>
    <arm_group_label>Group A</arm_group_label>
    <other_name>Electronic cigarette (nicotine/placebo)- Day 8</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Group B</intervention_name>
    <description>On days 7 and 8, subjects will be asked to inhale 10 puffs of a Blu brand e-cigarette (90 minutes prior to bronchoscopy on day 8). If the subject has no adverse effect to the e-cigarette he/she will again be asked to inhale 10 puffs of the Blu e-cigarette an hour later (30 minutes prior to bronchoscopy on day 8).</description>
    <arm_group_label>Group B</arm_group_label>
    <other_name>Electronic cigarette (nicotine/placebo)- Days 7 and 8</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Group C</intervention_name>
    <description>On days 6 through 8, subjects will be asked to inhale 10 puffs of a Blu brand e-cigarette (90 minutes prior to bronchoscopy on day 8). If the subject has no adverse effect to the e-cigarette he/she will again be asked to inhale 10 puffs of the Blu e-cigarette an hour later (30 minutes prior to bronchoscopy on day 8).</description>
    <arm_group_label>Group C</arm_group_label>
    <other_name>Electronic cigarette (nicotine/placebo) - Days 6 through 8</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Group D</intervention_name>
    <description>On days 5 through 8, subjects will be asked to inhale 10 puffs of a Blu brand e-cigarette (90 minutes prior to bronchoscopy on day 8). If the subject has no adverse effect to the e-cigarette he/she will again be asked to inhale 10 puffs of the Blu e-cigarette an hour later (30 minutes prior to bronchoscopy on day 8).</description>
    <arm_group_label>Group D</arm_group_label>
    <other_name>Electronic cigarette (nicotine/placebo)- Days 5 through 8</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Group E</intervention_name>
    <description>On days 4 through 8, subjects will be asked to inhale 10 puffs of a Blu brand e-cigarette (90 minutes prior to bronchoscopy on day 8). If the subject has no adverse effect to the e-cigarette he/she will again be asked to inhale 10 puffs of the Blu e-cigarette an hour later (30 minutes prior to bronchoscopy on day 8).&#xD;
Exposure to e-cigarettes will be limited to the nicotine equivalent of 1/2 pack of cigarettes to mitigate the risk of addiction to nicotine.</description>
    <arm_group_label>Group E</arm_group_label>
    <other_name>Electronic cigarette (nicotine/placebo) - Days 4 through 8</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Males and females, age 21 or older&#xD;
&#xD;
          -  Must be capable of providing informed consent&#xD;
&#xD;
          -  Self-reported never-smokers, with current smoking status validated by the absence of&#xD;
             nicotine metabolites in urine (nicotine &lt;2 ng/ml and cotinine &lt;5 ng/ml)&#xD;
&#xD;
          -  Normal physical examination&#xD;
&#xD;
          -  Good overall health without history of chronic lung disease, including asthma, and&#xD;
             without recurrent or recent (within 3 months) acute pulmonary disease&#xD;
&#xD;
          -  Normal routine laboratory evaluation, including general hematologic studies, general&#xD;
             serologic/immunologic studies, general biochemical analyses, and urine analysis&#xD;
&#xD;
          -  Not taking any medications relevant to lung disease or having an effect on the airway&#xD;
             epithelium&#xD;
&#xD;
          -  Negative HIV serology&#xD;
&#xD;
          -  Normal chest X-ray (PA and lateral)&#xD;
&#xD;
          -  Normal electrocardiogram (sinus bradycardia, premature atrial contractions are&#xD;
             permissible)&#xD;
&#xD;
          -  Females - not pregnant&#xD;
&#xD;
          -  No history of allergies to medications to be used in the bronchoscopy procedure&#xD;
&#xD;
          -  Willingness to participate in the study&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Unable to meet the inclusion criteria&#xD;
&#xD;
          -  Current active infection or acute illness of any kind&#xD;
&#xD;
          -  Evidence of malignancy within the past 5 years&#xD;
&#xD;
          -  Current alcohol or drug abuse&#xD;
&#xD;
          -  Pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ronald G Crystal, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Weill Medical College of Cornell University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Weill Cornell Medical College</name>
      <address>
        <city>New York</city>
        <state>New York</state>
        <zip>10065</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 2, 2014</study_first_submitted>
  <study_first_submitted_qc>July 9, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">July 11, 2014</study_first_posted>
  <last_update_submitted>July 22, 2020</last_update_submitted>
  <last_update_submitted_qc>July 22, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 24, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>E-Cigarettes</keyword>
  <keyword>Lung</keyword>
  <keyword>Non-Smokers</keyword>
  <keyword>Lung Biology</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Lung Diseases</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Nicotine</mesh_term>
  </intervention_browse>
  <patient_data>
    <sharing_ipd>Undecided</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/NCT02188511
org study id: 1312014623
nct id: NCT02188511
lead sponsor: 
has dmc: Yes
E-cigarettes are an increasingly popular alternate nicotine delivery system, but nothing is
      known about the effects of electronic cigarettes on the lungs. We hypothesize that
      e-cigarettes disorder airway epithelial and alveolar macrophages biology. Our goal is not to
      carry out a large epidemiologic study of electronic cigarette users to study lung function
      and other possible abnormal clinical phenotypes, but rather to focus on whether electronic
      cigarette smoke disorders the biology of the lung cells first exposed to the electronic
      cigarette smoke, a parameter that is the precursor of abnormalities in lung function and
      which is far more sensitive than lung function.
The specific aim of this study is to assess the hypothesis that electronic smoking disorders
      the biology of the airway epithelium and alveolar macrophages, to evaluate these changes in
      the lungs of normal nonsmokers exposed to electronic cigarettes, and to directly determine if
      the inhaled smoke from electronic cigarettes disturbs the biology of the naïve lung that has
      not been exposed to tobacco products. Because nicotine can be addictive with continual use,
      we will limit the exposure to a maximum of a nicotine equivalent of 1/2 pack of cigarettes
      over a 5 day period, a level that has been used safely in studies of healthy nonsmokers'
      naïve to nicotine.

      To obtain the most unbiased data about the effect of electronic cigarette use on the lung,
      normal nonsmokers will be briefly exposed to electronic cigarettes and lung cells, airway
      epithelium and alveolar macrophages, lung epithelial lining fluid (ELF) and serum will be
      collected before and after e-cigarette exposure. There will be 5 study groups consisting of
      10 non-smoker subjects (A-E), with each group undergoing an increased exposure to the amount
      of e-cigarettes (Group a being the lowest exposure, group E being the highest). Six of the
      subjects in each group will be exposed to e-cigarettes with nicotine while the remaining four
      in each group being exposed to nicotine-free e-cigarettes. Subjects will be assigned to use
      electronic cigarettes that either do or do not contain nicotine in a randomized, blinded
      manner.

      The duration of which the subjects will be observed for e-cigarette exposure will be 8 days.
      Baselines for each group will be established on Day 1 in which all subjects will undergo a
      bronchoscopy and an assessment of vital signs.

      For subjects in group A, at the day 8 visit after the vital signs are assessed, 3 hours prior
      to bronchoscopy, the subject will be asked to inhale 10 puffs of a "Blu" brand e-cigarette
      (for the nicotine-containing e-cigarette, this is approximately equivalent to < 1 cigarette).
      At 2 hours prior to the bronchoscopy procedure, if the subject has no adverse effect to the
      e-cigarette he/she will again be asked to inhale 10 puffs of the "Blu" e-cigarette. The vital
      signs will again be confirmed and any symptoms assessed prior to proceeding with
      bronchoscopy. Subjects in group B will undergo an identical exposure, but on both days 7 and
      8. Subjects in group C will undergo similar exposure on days 6-8, group D on days 5-8, and
      group E days 4-8 for a maximum of 5 exposure days prior to bronchoscopy. The research team
      will contact subjects at 1 month and 6 months after their Day 8 bronchoscopy in order to
      determine whether or not they have become dependent on nicotine.
allocation: Randomized
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: Double (Participant, Investigator)
measure: Airway epithelium and aveolar macrophage
time frame: 8 days
description: Changes in airway epithelium and aveolar macrophage will be measured by bronchoscopy
arm group label: Group A
arm group type: Experimental
description: Electronic cigarette (nicotine/placebo) - Day 8 Intervention: Electronic cigarette exposure will be limited to one day.
arm group label: Group B
arm group type: Experimental
description: Electronic cigarette (nicotine/placebo) - Days 7 through 8 Electronic cigarette exposure will be limited to two days
arm group label: Group C
arm group type: Experimental
description: Electronic cigarette (nicotine/placebo) - Days 6 through 8 Electronic cigarette exposure will be limited to 3 days
arm group label: Group D
arm group type: Experimental
description: Electronic cigarette (nicotine/placebo) - Days 5 through 8 Electronic cigarette exposure will be limited to 4 days
arm group label: Group E
arm group type: Experimental
description: Electronic cigarette (nicotine/placebo) - Days 4 through 8 Electronic cigarette exposure will be limited to 5 days.
intervention type: Other
intervention name: Group A
description: 90 minutes prior to the bronchoscopy on day 8, the subject will be asked to inhale 10 puffs of a Blu brand e-cigarette (for the nicotine-containing e-cigarette, this is approximately equivalent to < 1 cigarette). At 30 minutes prior to the bronchoscopy procedure if the subject has no adverse effect to the e-cigarette he/she will again be asked to inhale 10 puffs of the Blu e-cigarette.
arm group label: Group A
other name: Electronic cigarette (nicotine/placebo)- Day 8
intervention type: Other
intervention name: Group B
description: On days 7 and 8, subjects will be asked to inhale 10 puffs of a Blu brand e-cigarette (90 minutes prior to bronchoscopy on day 8). If the subject has no adverse effect to the e-cigarette he/she will again be asked to inhale 10 puffs of the Blu e-cigarette an hour later (30 minutes prior to bronchoscopy on day 8).
arm group label: Group B
other name: Electronic cigarette (nicotine/placebo)- Days 7 and 8
intervention type: Other
intervention name: Group C
description: On days 6 through 8, subjects will be asked to inhale 10 puffs of a Blu brand e-cigarette (90 minutes prior to bronchoscopy on day 8). If the subject has no adverse effect to the e-cigarette he/she will again be asked to inhale 10 puffs of the Blu e-cigarette an hour later (30 minutes prior to bronchoscopy on day 8).
arm group label: Group C
other name: Electronic cigarette (nicotine/placebo) - Days 6 through 8
intervention type: Other
intervention name: Group D
description: On days 5 through 8, subjects will be asked to inhale 10 puffs of a Blu brand e-cigarette (90 minutes prior to bronchoscopy on day 8). If the subject has no adverse effect to the e-cigarette he/she will again be asked to inhale 10 puffs of the Blu e-cigarette an hour later (30 minutes prior to bronchoscopy on day 8).
arm group label: Group D
other name: Electronic cigarette (nicotine/placebo)- Days 5 through 8
intervention type: Other
intervention name: Group E
description: On days 4 through 8, subjects will be asked to inhale 10 puffs of a Blu brand e-cigarette (90 minutes prior to bronchoscopy on day 8). If the subject has no adverse effect to the e-cigarette he/she will again be asked to inhale 10 puffs of the Blu e-cigarette an hour later (30 minutes prior to bronchoscopy on day 8).
Exposure to e-cigarettes will be limited to the nicotine equivalent of 1/2 pack of cigarettes to mitigate the risk of addiction to nicotine.
arm group label: Group E
other name: Electronic cigarette (nicotine/placebo) - Days 4 through 8
criteria: 
gender: All
minimum age: 21 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ronald G Crystal, MD
role: Principal Investigator
affiliation: Weill Medical College of Cornell University
facility: 
country: United States
responsible party type: Sponsor
mesh term: Lung Diseases
mesh term: Nicotine
sharing ipd: Undecided