Short-Term Cardiovascular Effects of E-Cigarettes: Influence of Device Power

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Short-Term Cardiovascular Effects of E-Cigarettes: Influence of Device Power

Conditions
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Cardiovascular Risk Factor, Nicotine Dependence

Intervention / Treatment
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* Other: Electronic Cigarette


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Use e-cigarettes on at least 25 days in the past 30 for at least 3 months and have not used another tobacco product in the past 30 days Healthy on the basis of medical history and limited physical examination (screening visit), as described below: Heart rate < 105 beats per minute (BPM)* Systolic Blood Pressure < 160 and > 90* Diastolic Blood Pressure < 100 and > 50* Body Mass Index (BMI) ≤ 38.0 (at investigator's discretion for higher BMI if no other concurrent health issues) *Considered out of range if both machine and manual readings are above/below these thresholds. Any race/ethnicity Exclusion Criteria: Used tobacco products other than e-cigarettes in past 30 days Expired carbon monoxide of over 5 ppm at screening The following unstable medical conditions: Heart disease Uncontrolled hypertension Thyroid disease (not hypo or hyper, controlled with medication) Diabetes Hepatitis B or C or Liver disease Glaucoma Prostatic hypertrophy Psychiatric conditions: Current or past schizophrenia, and/or current or past bipolar disorder Adult onset attention deficit hyperactivity disorder (ADHD) (if being treated) Participants with current or past depression and/or anxiety disorders will be reviewed by the study physician and considered for inclusion Psychiatric hospitalizations are not exclusionary, but study participation will be determined as per study physician's approval Drug/Alcohol Dependence: Alcohol or illicit drug dependence within the past 12 months with the exception of those who have recently completed an alcohol/drug treatment program Positive toxicology test at the screening visit (THC & prescribed medications okay) Opioid replacement therapy Positive urine cannabis is not exclusionary but participant must report use of cannabis in any form on not more than 2 times per week to be eligible Psychiatric medications: Current regular use of any psychiatric medications with the exception of Selective Serotonin Reuptake Inhibitor (SSRI) and serotonin-norepinephrine reuptake Inhibitor (SNRIs) and current evaluation by the study physician that the participant is otherwise healthy, stable, and able to participate. Medications Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6 (Example: rifampicin, dexamethasone, phenobarbital, and other anticonvulsant drugs). Concurrent use of nicotine-containing medications Other/Misc. Chronic Health Conditions Oral thrush Fainting Untreated thyroid disease Other life threatening illnesses as per study physician's discretion Pregnancy Pregnancy (self-reported and urine pregnancy test) Breastfeeding (determined by self-report) Concurrent participation in another clinical trial Inability to communicate in English Planning to quit smoking or vaping within the next 60 days

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Interventional Model Description: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Power level 10, 15, or 20 watts<br>Using an electronic cigarette, the patient will participate in a standardized vaping session using 1 of 3 assigned battery power levels | Other: Electronic Cigarette<br>* 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.<br>|
| Other: 1 of the other 2 remaining power levels<br>Using an electronic cigarette, the patient will participate in a standardized vaping session using 1 of the other 2 remaining power levels | Other: Electronic Cigarette<br>* 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.<br>|
| Other: Remaining power level<br>Using an electronic cigarette, the patient will participate in a standardized vaping session using the remaining power level | Other: Electronic Cigarette<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nicotine Exposure | Concentration of plasma nicotine (ng/ml) will be used to assess differences across the three power levels. | Day 1 of each Arm | 
| Subjective Effects: Withdrawal | 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. | Days 1-2 of each Arm | 
| Subjective Effects: Craving | 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. | Days 1-2 of each Arm | 
| Subjective Effects: Reward | 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. | Days 1-2 of each Arm | 
| Volatile Organic Compounds (VOC) Exposure | We will examine differences in 24-hour urine mercapturic acid metabolites of VOCs, particularly 3HPMA, the metabolite of acrolein across power settings | Day 2 of each Arm | 
| Cardiovascular Effects: Heart Rate | Participant heart rate will be measured in beats per minute throughout the inpatient stay. | Days 1-3 of each Arm | 
| Cardiovascular Effects: Blood Pressure | Participant systolic and diastolic blood pressure will be taken for 24 hours during ad-lib e-cigarette use. | Day 2 of each Arm | 
| Cardiovascular Effects: Epinephrine Excretion | Assays will be performed on participant urine samples to measure the presence of epinephrine metabolites in the form of catecholamines, in ng/ml. | Days 1-2 of each Arm | 
| Cardiovascular Effects: Biomarkers of Oxidative Stress | Assays will be performed on participant urine samples to measure oxidative stress-related constituents F2-isoprostane and 11-dTXB2 in ng/ml. | Days 1-2 of each Arm | 
| Cardiovascular Effects: Biomarkers of Inflammation | 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. | Day 1-2 of each Arm | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaping Topography: Puff Number | 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. | Day 1 of each Arm | 
| Vaping Topography: Puff Duration | 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. | Day 1 of each Arm | 
| Vaping Topography: Inter-Puff Interval | 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. | Day 1 of each Arm | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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E-Cigarettes, Vaping, E-Cig Mods