<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/NCT03839745</url>
  </required_header>
  <id_info>
    <org_study_id>1723965</org_study_id>
    <secondary_id>2U54CA180890-06</secondary_id>
    <secondary_id>NCI-2021-01564</secondary_id>
    <nct_id>NCT03839745</nct_id>
  </id_info>
  <brief_title>Short-Term Cardiovascular Effects of E-Cigarettes: Influence of Device Power</brief_title>
  <acronym>TCORS-1</acronym>
  <official_title>Short-Term Cardiovascular Effects of E-Cigarettes: Influence of Device Power</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of California, San Francisco</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Food and Drug Administration (FDA)</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Cancer Institute (NCI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will examine the short-term cardiovascular (CV) effects of e-cigarette device&#xD;
      power in a randomized, crossover clinical and behavioral pharmacology study of experienced&#xD;
      adult e-cigarette users (N=21). The specific aim is to determine the impact of e-cigarette&#xD;
      power on nicotine pharmacology, systemic exposure to toxic volatile organic compounds (VOCs),&#xD;
      and short-term cardiovascular effects.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a single-site, randomized, crossover study of experienced adult e-cigarette users to&#xD;
      assess nicotine exposure, toxicant exposure, and the short-term CV effects of e-cigarette&#xD;
      power. Three power levels will be assessed on all participants: 10, 15, and 20 watts.&#xD;
&#xD;
      Hypothesis 1a: Systemic nicotine exposure and subjective measures of sensation in the throat,&#xD;
      reward, and satisfaction will increase with increasing power in the e-cigarette device.&#xD;
&#xD;
      Hypothesis 1b: Mercapturic acid metabolites of volatile organic compounds (VOCs),&#xD;
      particularly acrolein, will increase with e-cigarette power.&#xD;
&#xD;
      Hypothesis 1c: CV effects increase with higher power, and are manifested as changes in&#xD;
      hemodynamic parameters, hormonal release, and biomarkers of endothelial function, platelet&#xD;
      activation, inflammation, and oxidative stress.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 26, 2019</start_date>
  <completion_date type="Actual">December 31, 2021</completion_date>
  <primary_completion_date type="Actual">December 31, 2021</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Crossover Assignment</intervention_model>
    <intervention_model_description>Crossover Assignment</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Nicotine Exposure</measure>
    <time_frame>Day 1 of each Arm</time_frame>
    <description>Concentration of plasma nicotine (ng/ml) will be used to assess differences across the three power levels.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Subjective Effects: Withdrawal</measure>
    <time_frame>Days 1-2 of each Arm</time_frame>
    <description>We will compile a score for the subjective effect of withdrawal using the sum of points scored on the Minnesota Nicotine Withdrawal Scale (MNWS), where a higher score (score range from 0 points to 60 points) indicates a higher intensity of the indicated subjective effect.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Subjective Effects: Craving</measure>
    <time_frame>Days 1-2 of each Arm</time_frame>
    <description>We will compile a score for the subjective effect of craving using the sum of points scored in the two subscales (intention and desire to engage in smoking behavior that is anticipated as pleasant, and anticipation of relief from negative affect through smoking) of the Questionnaire of Smoking Urges (QSU-Brief), where a higher score (score range from 10 points to 70 points) indicates a higher intensity of the indicated subjective effect.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Subjective Effects: Reward</measure>
    <time_frame>Days 1-2 of each Arm</time_frame>
    <description>We will compile a score for the subjective effect of reward using the sum of points scored in the five subscales (Smoking Satisfaction - score range from 1 point to 7 points; Psychological Reward - score range from 5 points to 35 points; Aversion - score range from 2 points to 14 points; Enjoyment of Respiratory Tract Sensations - score range from 2 points to 14 points; and Craving Reduction - score range from 1 point to 7 points) of the modified Cigarette Evaluation Scale (mCES), where a higher score indicates a higher intensity of the indicated subjective effect.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Volatile Organic Compounds (VOC) Exposure</measure>
    <time_frame>Day 2 of each Arm</time_frame>
    <description>We will examine differences in 24-hour urine mercapturic acid metabolites of VOCs, particularly 3HPMA, the metabolite of acrolein across power settings</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cardiovascular Effects: Heart Rate</measure>
    <time_frame>Days 1-3 of each Arm</time_frame>
    <description>Participant heart rate will be measured in beats per minute throughout the inpatient stay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cardiovascular Effects: Blood Pressure</measure>
    <time_frame>Day 2 of each Arm</time_frame>
    <description>Participant systolic and diastolic blood pressure will be taken for 24 hours during ad-lib e-cigarette use.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cardiovascular Effects: Epinephrine Excretion</measure>
    <time_frame>Days 1-2 of each Arm</time_frame>
    <description>Assays will be performed on participant urine samples to measure the presence of epinephrine metabolites in the form of catecholamines, in ng/ml.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cardiovascular Effects: Biomarkers of Oxidative Stress</measure>
    <time_frame>Days 1-2 of each Arm</time_frame>
    <description>Assays will be performed on participant urine samples to measure oxidative stress-related constituents F2-isoprostane and 11-dTXB2 in ng/ml.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cardiovascular Effects: Biomarkers of Inflammation</measure>
    <time_frame>Day 1-2 of each Arm</time_frame>
    <description>Assays will be performed on participant blood samples to measure cardiovascular inflammation-related constituents Interleukin 6 (IL-6), Vascular endothelial growth factor (VEGF), and Soluble intercellular adhesion molecule-1 (sICAM-1) in ng/ml.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Vaping Topography: Puff Number</measure>
    <time_frame>Day 1 of each Arm</time_frame>
    <description>Vaping topography measures will be obtained from frame by frame analysis of high definition videos during the ad libitum sessions and measured as puffs per minute.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vaping Topography: Puff Duration</measure>
    <time_frame>Day 1 of each Arm</time_frame>
    <description>Vaping topography measures will be obtained from frame by frame analysis of high definition videos during the ad libitum sessions and measured as seconds per puff.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Vaping Topography: Inter-Puff Interval</measure>
    <time_frame>Day 1 of each Arm</time_frame>
    <description>Vaping topography measures will be obtained from frame by frame analysis of high definition videos during the ad libitum sessions and measured as seconds/minutes between puffs.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">16</enrollment>
  <condition>Cardiovascular Risk Factor</condition>
  <condition>Nicotine Dependence</condition>
  <arm_group>
    <arm_group_label>Power level 10, 15, or 20 watts</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Using an electronic cigarette, the patient will participate in a standardized vaping session using 1 of 3 assigned battery power levels</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1 of the other 2 remaining power levels</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Using an electronic cigarette, the patient will participate in a standardized vaping session using 1 of the other 2 remaining power levels</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Remaining power level</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Using an electronic cigarette, the patient will participate in a standardized vaping session using the remaining power level</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Electronic Cigarette</intervention_name>
    <description>E-cigarette Device: The delivery device will be a variable wattage all-in-one device with operating wattage of 7.0 - 75.0 W, which is inclusive of the three power levels we intend to study.</description>
    <arm_group_label>1 of the other 2 remaining power levels</arm_group_label>
    <arm_group_label>Power level 10, 15, or 20 watts</arm_group_label>
    <arm_group_label>Remaining power level</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Use e-cigarettes on at least 25 days in the past 30 for at least 3 months and have not&#xD;
             used another tobacco product in the past 30 days&#xD;
&#xD;
          -  Healthy on the basis of medical history and limited physical examination (screening&#xD;
             visit), as described below:&#xD;
&#xD;
          -  Heart rate &lt; 105 beats per minute (BPM)*&#xD;
&#xD;
          -  Systolic Blood Pressure &lt; 160 and &gt; 90*&#xD;
&#xD;
          -  Diastolic Blood Pressure &lt; 100 and &gt; 50*&#xD;
&#xD;
          -  Body Mass Index (BMI) ≤ 38.0 (at investigator's discretion for higher BMI if no other&#xD;
             concurrent health issues)&#xD;
&#xD;
             *Considered out of range if both machine and manual readings are above/below these&#xD;
             thresholds.&#xD;
&#xD;
          -  Any race/ethnicity&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Used tobacco products other than e-cigarettes in past 30 days&#xD;
&#xD;
          -  Expired carbon monoxide of over 5 ppm at screening&#xD;
&#xD;
          -  The following unstable medical conditions:&#xD;
&#xD;
          -  Heart disease&#xD;
&#xD;
          -  Uncontrolled hypertension&#xD;
&#xD;
          -  Thyroid disease (not hypo or hyper, controlled with medication)&#xD;
&#xD;
          -  Diabetes&#xD;
&#xD;
          -  Hepatitis B or C or Liver disease&#xD;
&#xD;
          -  Glaucoma&#xD;
&#xD;
          -  Prostatic hypertrophy&#xD;
&#xD;
          -  Psychiatric conditions:&#xD;
&#xD;
          -  Current or past schizophrenia, and/or current or past bipolar disorder&#xD;
&#xD;
          -  Adult onset attention deficit hyperactivity disorder (ADHD) (if being treated)&#xD;
&#xD;
          -  Participants with current or past depression and/or anxiety disorders will be reviewed&#xD;
             by the study physician and considered for inclusion&#xD;
&#xD;
          -  Psychiatric hospitalizations are not exclusionary, but study participation will be&#xD;
             determined as per study physician's approval&#xD;
&#xD;
          -  Drug/Alcohol Dependence:&#xD;
&#xD;
          -  Alcohol or illicit drug dependence within the past 12 months with the exception of&#xD;
             those who have recently completed an alcohol/drug treatment program&#xD;
&#xD;
          -  Positive toxicology test at the screening visit (THC &amp; prescribed medications okay)&#xD;
&#xD;
          -  Opioid replacement therapy&#xD;
&#xD;
          -  Positive urine cannabis is not exclusionary but participant must report use of&#xD;
             cannabis in any form on not more than 2 times per week to be eligible&#xD;
&#xD;
          -  Psychiatric medications:&#xD;
&#xD;
          -  Current regular use of any psychiatric medications with the exception of Selective&#xD;
             Serotonin Reuptake Inhibitor (SSRI) and serotonin-norepinephrine reuptake Inhibitor&#xD;
             (SNRIs) and current evaluation by the study physician that the participant is&#xD;
             otherwise healthy, stable, and able to participate.&#xD;
&#xD;
          -  Medications&#xD;
&#xD;
          -  Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6 (Example:&#xD;
             rifampicin, dexamethasone, phenobarbital, and other anticonvulsant drugs).&#xD;
&#xD;
          -  Concurrent use of nicotine-containing medications&#xD;
&#xD;
          -  Other/Misc. Chronic Health Conditions&#xD;
&#xD;
          -  Oral thrush&#xD;
&#xD;
          -  Fainting&#xD;
&#xD;
          -  Untreated thyroid disease&#xD;
&#xD;
          -  Other &quot;life threatening illnesses&quot; as per study physician's discretion&#xD;
&#xD;
          -  Pregnancy&#xD;
&#xD;
          -  Pregnancy (self-reported and urine pregnancy test)&#xD;
&#xD;
          -  Breastfeeding (determined by self-report)&#xD;
&#xD;
          -  Concurrent participation in another clinical trial&#xD;
&#xD;
          -  Inability to communicate in English&#xD;
&#xD;
          -  Planning to quit smoking or vaping within the next 60 days&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gideon St. Helen, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of California, San Francisco</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Zuckerberg San Francisco General Hospital</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94110</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of California, San Francisco</name>
      <address>
        <city>San Francisco</city>
        <state>California</state>
        <zip>94143</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>January 2022</verification_date>
  <study_first_submitted>January 24, 2019</study_first_submitted>
  <study_first_submitted_qc>February 11, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 15, 2019</study_first_posted>
  <last_update_submitted>February 22, 2022</last_update_submitted>
  <last_update_submitted_qc>February 22, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">February 24, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>E-Cigarettes</keyword>
  <keyword>Vaping</keyword>
  <keyword>E-Cig Mods</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tobacco Use Disorder</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>December 10, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/45/NCT03839745/Prot_002.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>November 19, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/45/NCT03839745/ICF_004.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <!-- 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/NCT03839745
org study id: 1723965
secondary id: 2U54CA180890-06
secondary id: NCI-2021-01564
nct id: NCT03839745
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
This study will examine the short-term cardiovascular (CV) effects of e-cigarette device
      power in a randomized, crossover clinical and behavioral pharmacology study of experienced
      adult e-cigarette users (N=21). The specific aim is to determine the impact of e-cigarette
      power on nicotine pharmacology, systemic exposure to toxic volatile organic compounds (VOCs),
      and short-term cardiovascular effects.
This is a single-site, randomized, crossover study of experienced adult e-cigarette users to
      assess nicotine exposure, toxicant exposure, and the short-term CV effects of e-cigarette
      power. Three power levels will be assessed on all participants: 10, 15, and 20 watts.

      Hypothesis 1a: Systemic nicotine exposure and subjective measures of sensation in the throat,
      reward, and satisfaction will increase with increasing power in the e-cigarette device.

      Hypothesis 1b: Mercapturic acid metabolites of volatile organic compounds (VOCs),
      particularly acrolein, will increase with e-cigarette power.

      Hypothesis 1c: CV effects increase with higher power, and are manifested as changes in
      hemodynamic parameters, hormonal release, and biomarkers of endothelial function, platelet
      activation, inflammation, and oxidative stress.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Nicotine Exposure
time frame: Day 1 of each Arm
description: Concentration of plasma nicotine (ng/ml) will be used to assess differences across the three power levels.
measure: Subjective Effects: Withdrawal
time frame: Days 1-2 of each Arm
description: We will compile a score for the subjective effect of withdrawal using the sum of points scored on the Minnesota Nicotine Withdrawal Scale (MNWS), where a higher score (score range from 0 points to 60 points) indicates a higher intensity of the indicated subjective effect.
measure: Subjective Effects: Craving
time frame: Days 1-2 of each Arm
description: We will compile a score for the subjective effect of craving using the sum of points scored in the two subscales (intention and desire to engage in smoking behavior that is anticipated as pleasant, and anticipation of relief from negative affect through smoking) of the Questionnaire of Smoking Urges (QSU-Brief), where a higher score (score range from 10 points to 70 points) indicates a higher intensity of the indicated subjective effect.
measure: Subjective Effects: Reward
time frame: Days 1-2 of each Arm
description: We will compile a score for the subjective effect of reward using the sum of points scored in the five subscales (Smoking Satisfaction - score range from 1 point to 7 points; Psychological Reward - score range from 5 points to 35 points; Aversion - score range from 2 points to 14 points; Enjoyment of Respiratory Tract Sensations - score range from 2 points to 14 points; and Craving Reduction - score range from 1 point to 7 points) of the modified Cigarette Evaluation Scale (mCES), where a higher score indicates a higher intensity of the indicated subjective effect.
measure: Volatile Organic Compounds (VOC) Exposure
time frame: Day 2 of each Arm
description: We will examine differences in 24-hour urine mercapturic acid metabolites of VOCs, particularly 3HPMA, the metabolite of acrolein across power settings
measure: Cardiovascular Effects: Heart Rate
time frame: Days 1-3 of each Arm
description: Participant heart rate will be measured in beats per minute throughout the inpatient stay.
measure: Cardiovascular Effects: Blood Pressure
time frame: Day 2 of each Arm
description: Participant systolic and diastolic blood pressure will be taken for 24 hours during ad-lib e-cigarette use.
measure: Cardiovascular Effects: Epinephrine Excretion
time frame: Days 1-2 of each Arm
description: Assays will be performed on participant urine samples to measure the presence of epinephrine metabolites in the form of catecholamines, in ng/ml.
measure: Cardiovascular Effects: Biomarkers of Oxidative Stress
time frame: Days 1-2 of each Arm
description: Assays will be performed on participant urine samples to measure oxidative stress-related constituents F2-isoprostane and 11-dTXB2 in ng/ml.
measure: Cardiovascular Effects: Biomarkers of Inflammation
time frame: Day 1-2 of each Arm
description: Assays will be performed on participant blood samples to measure cardiovascular inflammation-related constituents Interleukin 6 (IL-6), Vascular endothelial growth factor (VEGF), and Soluble intercellular adhesion molecule-1 (sICAM-1) in ng/ml.
measure: Vaping Topography: Puff Number
time frame: Day 1 of each Arm
description: Vaping topography measures will be obtained from frame by frame analysis of high definition videos during the ad libitum sessions and measured as puffs per minute.
measure: Vaping Topography: Puff Duration
time frame: Day 1 of each Arm
description: Vaping topography measures will be obtained from frame by frame analysis of high definition videos during the ad libitum sessions and measured as seconds per puff.
measure: Vaping Topography: Inter-Puff Interval
time frame: Day 1 of each Arm
description: Vaping topography measures will be obtained from frame by frame analysis of high definition videos during the ad libitum sessions and measured as seconds/minutes between puffs.
arm group label: Power level 10, 15, or 20 watts
arm group type: Other
description: Using an electronic cigarette, the patient will participate in a standardized vaping session using 1 of 3 assigned battery power levels
arm group label: 1 of the other 2 remaining power levels
arm group type: Other
description: Using an electronic cigarette, the patient will participate in a standardized vaping session using 1 of the other 2 remaining power levels
arm group label: Remaining power level
arm group type: Other
description: Using an electronic cigarette, the patient will participate in a standardized vaping session using the remaining power level
intervention type: Other
intervention name: Electronic Cigarette
description: E-cigarette Device: The delivery device will be a variable wattage all-in-one device with operating wattage of 7.0 - 75.0 W, which is inclusive of the three power levels we intend to study.
arm group label: 1 of the other 2 remaining power levels
arm group label: Power level 10, 15, or 20 watts
arm group label: Remaining power level
criteria: 
gender: All
minimum age: 21 Years
maximum age: N/A
healthy volunteers: Accepts Healthy Volunteers
last name: Gideon St. Helen, PhD
role: Principal Investigator
affiliation: University of California, San Francisco
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Tobacco Use Disorder
sharing ipd: No
provided document: 
provided document: 