Short-Term Cardiovascular Effects of E-Cigarettes: Influence of Device Power (TCORS-1)

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.

Study Overview

• Status: Completed
• Conditions: Cardiovascular Risk Factor; Nicotine Dependence
• Intervention / Treatment: Other: Electronic Cigarette

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • California
    • San Francisco, California, United States, 94143
      • University of California, San Francisco
    • San Francisco, California, United States, 94110
      • Zuckerberg San Francisco General Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of California, San Francisco
• Collaborators: National Cancer Institute (NCI); National Institutes of Health (NIH); Food and Drug Administration (FDA)
• Investigators: Principal Investigator: Gideon St. Helen, PhD, University of California, San Francisco

Study record dates

Study Major Dates

• Study Start (Actual): March 26, 2019
• Primary Completion (Actual): December 31, 2021
• Study Completion (Actual): December 31, 2021

Study Registration Dates

• First Submitted: January 24, 2019
• First Submitted That Met QC Criteria: February 11, 2019
• First Posted (Actual): February 15, 2019

Study Record Updates

• Last Update Posted (Actual): February 24, 2022
• Last Update Submitted That Met QC Criteria: February 22, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Keywords: Vaping; E-Cigarettes; E-Cig Mods
• Additional Relevant MeSH Terms: Mental Disorders; Chemically-Induced Disorders; Substance-Related Disorders; Tobacco Use Disorder
• Other Study ID Numbers: 1723965; 2U54CA180890-06 (U.S. NIH Grant/Contract); NCI-2021-01564 (Registry Identifier: NCI Clinical Trials Reporting Program (CTRP))

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No