<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/NCT04449510</url>
  </required_header>
  <id_info>
    <org_study_id>20-30597</org_study_id>
    <secondary_id>2U54CA180890-06</secondary_id>
    <secondary_id>U54HL147127</secondary_id>
    <nct_id>NCT04449510</nct_id>
  </id_info>
  <brief_title>Short-Term Cardiovascular Effects of E-Cigarettes: Influence of E-Liquid pH</brief_title>
  <acronym>TCORS-2</acronym>
  <official_title>Short-Term Cardiovascular Effects of E-Cigarettes: Influence of E-Liquid pH</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>
    <collaborator>
      <agency>National Heart, Lung, and Blood Institute (NHLBI)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>University of California, San Francisco</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <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-liquid pH in a&#xD;
      randomized, crossover clinical and behavioral pharmacology study of experienced adult&#xD;
      e-cigarette users (N=21). The specific aim of the study is to assess the impact of changes in&#xD;
      e-liquid pH on nicotine pharmacokinetics, cardiovascular, and subjective effects of&#xD;
      e-cigarettes.&#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-liquid pH.&#xD;
      Three e-liquid pH conditions will be assessed on all participants: 5, 7, and 9.&#xD;
&#xD;
      Hypothesis 2a: The rate of systemic nicotine absorption is inversely related to e-liquid pH&#xD;
      and results in lower peak blood nicotine levels at higher pH.&#xD;
&#xD;
      Hypothesis 2b: Heart rate acceleration will decrease and subjective measures of sensation in&#xD;
      the throat, reward, and satisfaction will increase with increasing e-liquid pH.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">January 4, 2021</start_date>
  <completion_date type="Anticipated">August 31, 2023</completion_date>
  <primary_completion_date type="Anticipated">August 31, 2023</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>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Nicotine Exposure: Blood Nicotine</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 e-liquid pH levels.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Nicotine Exposure: Saliva pH</measure>
    <time_frame>Day 1 of each Arm</time_frame>
    <description>Participant saliva pH will be measured before and during outpatient stay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Subjective Effects: Withdrawal</measure>
    <time_frame>Day 1 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>Day 1 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>Day 1 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>Cardiovascular Effects: Heart Rate</measure>
    <time_frame>Day 1 of each Arm</time_frame>
    <description>Participant heart rate will be measured in beats per minute throughout the outpatient stay.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Cardiovascular Effects: Skin Blood Flow</measure>
    <time_frame>Day 1 of each Arm</time_frame>
    <description>Participant skin blood flow will be measured by product of average blood cell velocity and concentration in mL/min during outpatient stay.</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="Anticipated">21</enrollment>
  <condition>Cardiovascular Risk Factor</condition>
  <condition>Nicotine Dependence</condition>
  <arm_group>
    <arm_group_label>E-liquid pH 5, 7, or 9</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 e-liquid pH.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>1 of the other 2 remaining e-liquid pH</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 assigned e-liquid pH.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Remaining e-liquid pH</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 assigned e-liquid pH.</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. The device will be set at 10 watts for the study visits.</description>
    <arm_group_label>1 of the other 2 remaining e-liquid pH</arm_group_label>
    <arm_group_label>E-liquid pH 5, 7, or 9</arm_group_label>
    <arm_group_label>Remaining e-liquid pH</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#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) &lt; 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;
          -  Use e-cigarettes on at least 15 days in the past 30 for at least 3 months&#xD;
&#xD;
          -  Smoke 10 or fewer cigarettes/tobacco products per day in the last 30 days&#xD;
&#xD;
          -  Willing to use mod e-cigarette&#xD;
&#xD;
          -  Willing to abstain from tobacco product use for night before study&#xD;
&#xD;
          -  Age: &gt; 21 years old and &lt; 70 years old&#xD;
&#xD;
          -  Using e-liquid &gt; 0mg/ml nicotine&#xD;
&#xD;
          -  Saliva cotinine of ≥ 30 ng/ml or NicAlert=6 (in cases where lab turn around time will&#xD;
             delay study procedure)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Seizures&#xD;
&#xD;
          -  Cancer&#xD;
&#xD;
          -  Hepatitis B or C or Liver Disease&#xD;
&#xD;
          -  Oral Thrush&#xD;
&#xD;
          -  Heart disease&#xD;
&#xD;
          -  Glaucoma&#xD;
&#xD;
          -  Kidney disease or urinary retention&#xD;
&#xD;
          -  Diabetes&#xD;
&#xD;
          -  High Blood Pressure (taking sympatholytic medications such as alpha and beta blockers)&#xD;
&#xD;
          -  History of stroke&#xD;
&#xD;
          -  An ulcer in the past year&#xD;
&#xD;
          -  Thyroid disease (okay if controlled with medication)&#xD;
&#xD;
          -  Active use of an inhaler for asthma or Chronic Obstructive Pulmonary Disease (COPD)&#xD;
&#xD;
          -  Psychiatric conditions&#xD;
&#xD;
          -  Current or past schizophrenia, and/or current or past bipolar disorder&#xD;
&#xD;
          -  Major depression, current or within the past year&#xD;
&#xD;
          -  Major personality disorder&#xD;
&#xD;
          -  Participants with current or past minor or moderate depression and/or anxiety&#xD;
             disorders will be reviewed by the study physician and considered for inclusion.&#xD;
&#xD;
          -  History of psychiatric hospitalizations are not exclusionary, but study participation&#xD;
             will be determined as per study physician's approval&#xD;
&#xD;
          -  Recent onset or change in cough, fever and/or abdominal symptoms (vomiting or pain) in&#xD;
             the past two weeks. (If yes, participant can re-screen when symptoms resolve).&#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 (including methadone, buprenorphine, or other)&#xD;
&#xD;
          -  Positive urine cannabis is not exclusionary but participant must report use of&#xD;
             cannabis and agree to abstain from cannabis use for the duration of the study&#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 CYP2A4 (Example:&#xD;
             rifampicin, carbamazepine, phenobarbital, and other anticonvulsant drugs).&#xD;
&#xD;
          -  Concurrent use of nicotine-containing medications&#xD;
&#xD;
          -  Any stimulant medications (example: Adderall) generally given for Attention deficit&#xD;
             hyperactivity disorder (ADHD) treatment&#xD;
&#xD;
          -  Use of sympatholytic medications that affect cardiovascular conditions including&#xD;
             hypertension, (Example: beta and alpha-blockers)&#xD;
&#xD;
          -  Other/Misc. Chronic Health Conditions&#xD;
&#xD;
          -  Fainting (within the last 30 days)&#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 vaping within the next 60 days&#xD;
&#xD;
          -  Uncomfortable with getting blood drawn&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>70 Years</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>
  <overall_contact>
    <last_name>Lisa Lawrence</last_name>
    <phone>(415) 608-4864</phone>
    <email>Lisa.Lawrence@ucsf.edu</email>
  </overall_contact>
  <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>
    <status>Recruiting</status>
    <contact>
      <last_name>Lisa Lawrence</last_name>
      <email>Lisa.Lawrence@ucsf.edu</email>
    </contact>
    <investigator>
      <last_name>Gideon St. Helen, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </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>
    <status>Recruiting</status>
    <contact>
      <last_name>Lisa Lawrence</last_name>
      <email>Lisa.Lawrence@ucsf.edu</email>
    </contact>
    <investigator>
      <last_name>Gideon St. Helen, PhD</last_name>
      <role>Principal Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>May 2023</verification_date>
  <study_first_submitted>June 24, 2020</study_first_submitted>
  <study_first_submitted_qc>June 24, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 26, 2020</study_first_posted>
  <last_update_submitted>May 22, 2023</last_update_submitted>
  <last_update_submitted_qc>May 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">May 24, 2023</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>
  <!-- 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/NCT04449510
org study id: 20-30597
secondary id: 2U54CA180890-06
secondary id: U54HL147127
nct id: NCT04449510
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study will examine the short-term cardiovascular (CV) effects of e-liquid pH in a
      randomized, crossover clinical and behavioral pharmacology study of experienced adult
      e-cigarette users (N=21). The specific aim of the study is to assess the impact of changes in
      e-liquid pH on nicotine pharmacokinetics, cardiovascular, and subjective effects of
      e-cigarettes.
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-liquid pH.
      Three e-liquid pH conditions will be assessed on all participants: 5, 7, and 9.

      Hypothesis 2a: The rate of systemic nicotine absorption is inversely related to e-liquid pH
      and results in lower peak blood nicotine levels at higher pH.

      Hypothesis 2b: Heart rate acceleration will decrease and subjective measures of sensation in
      the throat, reward, and satisfaction will increase with increasing e-liquid pH.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Nicotine Exposure: Blood Nicotine
time frame: Day 1 of each Arm
description: Concentration of plasma nicotine (ng/ml) will be used to assess differences across the three e-liquid pH levels.
measure: Nicotine Exposure: Saliva pH
time frame: Day 1 of each Arm
description: Participant saliva pH will be measured before and during outpatient stay.
measure: Subjective Effects: Withdrawal
time frame: Day 1 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: Day 1 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: Day 1 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: Cardiovascular Effects: Heart Rate
time frame: Day 1 of each Arm
description: Participant heart rate will be measured in beats per minute throughout the outpatient stay.
measure: Cardiovascular Effects: Skin Blood Flow
time frame: Day 1 of each Arm
description: Participant skin blood flow will be measured by product of average blood cell velocity and concentration in mL/min during outpatient stay.
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: E-liquid pH 5, 7, or 9
arm group type: Other
description: Using an electronic cigarette, the patient will participate in a standardized vaping session using 1 of 3 assigned e-liquid pH.
arm group label: 1 of the other 2 remaining e-liquid pH
arm group type: Other
description: Using an electronic cigarette, the patient will participate in a standardized vaping session using 1 of the other 2 assigned e-liquid pH.
arm group label: Remaining e-liquid pH
arm group type: Other
description: Using an electronic cigarette, the patient will participate in a standardized vaping session using the remaining assigned e-liquid pH.
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. The device will be set at 10 watts for the study visits.
arm group label: 1 of the other 2 remaining e-liquid pH
arm group label: E-liquid pH 5, 7, or 9
arm group label: Remaining e-liquid pH
criteria: 
gender: All
minimum age: 21 Years
maximum age: 70 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Gideon St. Helen, PhD
role: Principal Investigator
affiliation: University of California, San Francisco
last name: Lisa Lawrence
phone: (415) 608-4864
email: Lisa.Lawrence@ucsf.edu
facility: 
status: Recruiting
contact: 
investigator: 
facility: 
status: Recruiting
contact: 
investigator: 
country: United States
responsible party type: Sponsor
mesh term: Tobacco Use Disorder
sharing ipd: No