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

Study Overview
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Brief Summary
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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.

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-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.

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

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: 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

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 70 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: E-liquid pH 5, 7, or 9<br>Using an electronic cigarette, the patient will participate in a standardized vaping session using 1 of 3 assigned e-liquid pH. | 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. The device will be set at 10 watts for the study visits.<br>|
| Other: 1 of the other 2 remaining e-liquid pH<br>Using an electronic cigarette, the patient will participate in a standardized vaping session using 1 of the other 2 assigned e-liquid pH. | 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. The device will be set at 10 watts for the study visits.<br>|
| Other: Remaining e-liquid pH<br>Using an electronic cigarette, the patient will participate in a standardized vaping session using the remaining assigned e-liquid pH. | 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. The device will be set at 10 watts for the study visits.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| Nicotine Exposure: Saliva pH | Participant saliva pH will be measured before and during outpatient stay. | 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. | Day 1 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. | Day 1 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. | Day 1 of each Arm | 
| Cardiovascular Effects: Heart Rate | Participant heart rate will be measured in beats per minute throughout the outpatient stay. | Day 1 of each Arm | 
| 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 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