Short-Term Cardiovascular Effects of E-Cigarettes: Influence of E-Liquid pH

Nicotine Dependence Clinical Trial

— TCORS-2  

Official title:

Short-Term Cardiovascular Effects of E-Cigarettes: Influence of E-Liquid pH

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04449510
• Other study ID #: 20-30597
• Secondary ID: 2U54CA180890-06U
• Status: Recruiting
• Phase: N/A
• Start date: January 4, 2021
• Est. completion date: August 31, 2024

Study information

• Verified date: October 2023
• Source: University of California, San Francisco
• Contact: Lisa Lawrence
• Phone: (415) 608-4864
• Email: Lisa.Lawrence[@]ucsf.edu
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 21
• Est. completion date: August 31, 2024
• Est. primary completion date: August 31, 2024
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 21 Years to 70 Years

Eligibility

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

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. The device will be set at 10 watts for the study visits.

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 (5)

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

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Nicotine Exposure: Blood Nicotine	Concentration of plasma nicotine (ng/ml) will be used to assess differences across the three e-liquid pH levels.	Day 1 of each Arm
Primary	Nicotine Exposure: Saliva pH	Participant saliva pH will be measured before and during outpatient stay.	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.	Day 1 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.	Day 1 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.	Day 1 of each Arm
Primary	Cardiovascular Effects: Heart Rate	Participant heart rate will be measured in beats per minute throughout the outpatient stay.	Day 1 of each Arm
Primary	Cardiovascular Effects: Skin Blood Flow	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	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