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

Nicotine Dependence Clinical Trial

— TCORS-1  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03839745
• Other study ID #: 1723965
• Secondary ID: 2U54CA180890-06N
• Status: Completed
• Phase: N/A
• Start date: March 26, 2019
• Est. completion date: December 31, 2021

Study information

• Verified date: January 2022
• Source: University of California, San Francisco
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: December 31, 2021
• Est. primary completion date: December 31, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Risk Factor
• Nicotine Dependence
• Tobacco Use Disorder

Intervention

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.

Locations

Country	Name	City	State
United States	University of California, San Francisco	San Francisco	California
United States	Zuckerberg San Francisco General Hospital	San Francisco	California

Sponsors (4)

Lead Sponsor	Collaborator
University of California, San Francisco	Food and Drug Administration (FDA), National Cancer Institute (NCI), National Institutes of Health (NIH)

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nicotine Exposure	Concentration of plasma nicotine (ng/ml) will be used to assess differences across the three power levels.	Day 1 of each Arm
Primary	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
Primary	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
Primary	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
Primary	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
Primary	Cardiovascular Effects: Heart Rate	Participant heart rate will be measured in beats per minute throughout the inpatient stay.	Days 1-3 of each Arm
Primary	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
Primary	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
Primary	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
Primary	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	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
Secondary	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
Secondary	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