Short-Term Cardiovascular Effects of E-Cigarettes: Influence of E-Liquid pH (TCORS-2)

October 11, 2023 updated by: University of California, San Francisco
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.

Study Overview

Status

Recruiting

Intervention / Treatment

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-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.

Study Type

Interventional

Enrollment (Estimated)

21

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

    • California
      • San Francisco, California, United States, 94143
        • Recruiting
        • University of California, San Francisco
        • Contact:
        • Principal Investigator:
          • Gideon St. Helen, PhD
      • San Francisco, California, United States, 94110
        • Recruiting
        • Zuckerberg San Francisco General Hospital
        • Contact:
        • Principal Investigator:
          • Gideon St. Helen, PhD

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

21 years to 70 years (Adult, Older Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  • 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

  • Use e-cigarettes on at least 15 days in the past 30 for at least 3 months
  • Smoke 10 or fewer cigarettes/tobacco products per day in the last 30 days
  • Willing to use mod e-cigarette
  • Willing to abstain from tobacco product use for night before study
  • Age: > 21 years old and < 70 years old
  • Using e-liquid > 0mg/ml nicotine
  • Saliva cotinine of ≥ 30 ng/ml or NicAlert=6 (in cases where lab turn around time will delay study procedure)

Exclusion Criteria:

  • Seizures
  • Cancer
  • Hepatitis B or C or Liver Disease
  • Oral Thrush
  • Heart disease
  • Glaucoma
  • Kidney disease or urinary retention
  • Diabetes
  • High Blood Pressure (taking sympatholytic medications such as alpha and beta blockers)
  • History of stroke
  • An ulcer in the past year
  • Thyroid disease (okay if controlled with medication)
  • Active use of an inhaler for asthma or Chronic Obstructive Pulmonary Disease (COPD)
  • Psychiatric conditions
  • Current or past schizophrenia, and/or current or past bipolar disorder
  • Major depression, current or within the past year
  • Major personality disorder
  • Participants with current or past minor or moderate depression and/or anxiety disorders will be reviewed by the study physician and considered for inclusion.
  • History of psychiatric hospitalizations are not exclusionary, but study participation will be determined as per study physician's approval
  • Recent onset or change in cough, fever and/or abdominal symptoms (vomiting or pain) in the past two weeks. (If yes, participant can re-screen when symptoms resolve).
  • 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 (including methadone, buprenorphine, or other)
  • Positive urine cannabis is not exclusionary but participant must report use of cannabis and agree to abstain from cannabis use for the duration of the study
  • 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 CYP2A4 (Example: rifampicin, carbamazepine, phenobarbital, and other anticonvulsant drugs).
  • Concurrent use of nicotine-containing medications
  • Any stimulant medications (example: Adderall) generally given for Attention deficit hyperactivity disorder (ADHD) treatment
  • Use of sympatholytic medications that affect cardiovascular conditions including hypertension, (Example: beta and alpha-blockers)
  • Other/Misc. Chronic Health Conditions
  • Fainting (within the last 30 days)
  • 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 vaping within the next 60 days
  • Uncomfortable with getting blood drawn

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Other: E-liquid pH 5, 7, or 9
Using an electronic cigarette, the patient will participate in a standardized vaping session using 1 of 3 assigned e-liquid pH.
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.
Other: 1 of the other 2 remaining e-liquid pH
Using an electronic cigarette, the patient will participate in a standardized vaping session using 1 of the other 2 assigned e-liquid pH.
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.
Other: Remaining e-liquid pH
Using an electronic cigarette, the patient will participate in a standardized vaping session using the remaining assigned e-liquid pH.
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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Nicotine Exposure: Blood Nicotine
Time Frame: Day 1 of each Arm
Concentration of plasma nicotine (ng/ml) will be used to assess differences across the three e-liquid pH levels.
Day 1 of each Arm
Nicotine Exposure: Saliva pH
Time Frame: Day 1 of each Arm
Participant saliva pH will be measured before and during outpatient stay.
Day 1 of each Arm
Subjective Effects: Withdrawal
Time Frame: Day 1 of each Arm
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.
Day 1 of each Arm
Subjective Effects: Craving
Time Frame: Day 1 of each Arm
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.
Day 1 of each Arm
Subjective Effects: Reward
Time Frame: Day 1 of each Arm
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.
Day 1 of each Arm
Cardiovascular Effects: Heart Rate
Time Frame: Day 1 of each Arm
Participant heart rate will be measured in beats per minute throughout the outpatient stay.
Day 1 of each Arm
Cardiovascular Effects: Skin Blood Flow
Time Frame: Day 1 of each Arm
Participant skin blood flow will be measured by product of average blood cell velocity and concentration in mL/min during outpatient stay.
Day 1 of each Arm

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Vaping Topography: Puff Number
Time Frame: Day 1 of each Arm
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
Time Frame: Day 1 of each Arm
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
Time Frame: Day 1 of each Arm
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

This is where you will find people and organizations involved with this study.

Investigators

  • Principal Investigator: Gideon St. Helen, PhD, University of California, San Francisco

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 4, 2021

Primary Completion (Estimated)

August 31, 2024

Study Completion (Estimated)

August 31, 2024

Study Registration Dates

First Submitted

June 24, 2020

First Submitted That Met QC Criteria

June 24, 2020

First Posted (Actual)

June 26, 2020

Study Record Updates

Last Update Posted (Actual)

October 12, 2023

Last Update Submitted That Met QC Criteria

October 11, 2023

Last Verified

October 1, 2023

More Information

Terms related to this study

Other Study ID Numbers

  • 20-30597
  • 2U54CA180890-06 (U.S. NIH Grant/Contract)
  • U54HL147127 (U.S. NIH Grant/Contract)

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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