Vaping High vs. Low Nicotine E-Liquid

Study Overview
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Brief Summary
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This study will examine the effects of electronic cigarette e-liquid nicotine content in a randomized, crossover clinical and behavioral pharmacology study of experienced adult e-cigarette users (N=36). The specific aim is to determine the impact of nicotine content of e-liquid on nicotine pharmacology, systemic exposure to toxic volatile organic compounds, and short-term cardiovascular effects.

Detailed Description
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This is a within-subjects, crossover design of advanced electronic cigarette users in which we will examine nicotine pharmacokinetics, subjective effects, daily nicotine intake and nicotine titration, short-term cardiovascular effects, and toxicant exposure when participants are using low vs. high nicotine e-liquids. Hypothesis 1: E-cigarette users will titrate their intake of nicotine such that they will inhale fewer aerosol toxicants and suffer less harm to health when using higher vs. lower nicotine content e-liquids. Hypothesis 2: Compared to low nicotine, high nicotine e-liquid use will have similar cardiovascular effects throughout the day (due to compensatory behavioral changes), with similar effects on heart rate, blood pressure, and catecholamine release. Hypothesis 3: Exposure to volatile organic compounds (VOCs) will be lower when vaping high nicotine e-liquids compared to low nicotine e-liquids.

Official Title
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Vaping High vs. Low Nicotine E-Liquid

Conditions
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Nicotine Dependence, Cardiovascular Risk Factor

Intervention / Treatment
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* Other: Low Nicotine E-Liquid
* Other: Medium or High Nicotine E-Liquid


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy on the basis of medical history and limited physical examination, as described below: Heart rate < 105 beats per minute (BPM)* Systolic Blood Pressure < 160 and > 90* Diastolic Blood Pressure < 100 and > 50* *Considered out of range if both machine and manual readings are above/below these thresholds. Age: >= 21 years Age: <= 70 years Current regular user of open tank electronic cigarette (EC) (at least 20 times in the past 30 days) with e-liquid nicotine of 3-6 mg/mL. Non-smoker or non-daily cigarette smokers agreeing to abstain from cigarettes for the duration of the study. Saliva cotinine >50 ng/mL and/or NicAlert=6 Carbon monoxide >= 5 ppm or per discretion of Principal Investigator Exclusion Criteria: Medical Heart disease Seizures Cancer Thyroid disease (okay if controlled with medication) Diabetes Hepatitis B or C or Liver disease Glaucoma Kidney disease or urinary retention History of stroke An ulcer in the past year 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 PI and considered for inclusion History of psychiatric hospitalizations is not exclusionary, but study participation will be determined as per PI'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 for illicit drugs at the screening visit (THC & prescribed medications okay) Opioid replacement therapy (including methadone, buprenorphine, or other) Psychiatric medications Current regular use of any psychiatric medications with the exception of Selective Serotonin Reuptake Inhibitors (SSRIs) and serotonin-norepinephrine reuptake Inhibitors (SNRIs) and current evaluation by the PI 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, carbamazepine, phenobarbital, and other anticonvulsant drugs). Use of sympatholytic medications for cardiovascular conditions including hypertension (Example: beta and alpha-blockers) Concurrent use of nicotine-containing medications Any stimulant medications (example: Adderall) generally given for attention deficit hyperactivity disorder (ADHD) treatment Other/Misc. Chronic Health Conditions Oral thrush Fainting (within the last 30 days) Other life threatening illnesses as per PI's discretion Pregnancy Pregnancy (self-reported and urine pregnancy test) Breastfeeding (determined by self-report) Concurrent participation in another clinical trial Inability to read and write in English Planning to quit vaping within the next 60 days Concurrent regular use of marijuana (occasional users of these products may be enrolled if they agree to abstain from their use during the period of the study) Use of other tobacco products, smokeless tobacco, pipes, cigars/cigarillos, blunts/spliffs (no more than 10 times in the past month and must agree to abstain from their use during the period of the study)

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
Interventional Model Description: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Low Nicotine<br>Using an electronic cigarette, the patient will participate in a standardized vaping session using 3 mg/ml nicotine e-liquid. | Other: Low Nicotine E-Liquid<br>* Participants will vape e-liquid with nicotine concentration of 3 mg/ml.<br>|
| Other: Medium or High Nicotine<br>The patient will participate in a standardized vaping session using either an electronic cigarette with 18 mg/ml nicotine e-liquid or a JUUL device with a JUUL e-liquid pod. | Other: Medium or High Nicotine E-Liquid<br>* Participants will vape either e-liquid with nicotine concentration of 18 mg/ml or a JUUL device with JUUL pod of 59 mg/ml nicotine e-liquid.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Nicotine Exposure | Plasma nicotine area under curve (AUC) (ng/ml*h) | Day 1 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: Systolic Blood Pressure | Participant systolic blood pressure will be taken for 24 hours during ad-lib e-cigarette use. | Day 2 of each Arm | 
| Cardiovascular Effects: Diastolic Blood Pressure | Participant diastolic blood pressure will be taken for 24 hours during ad-lib e-cigarette use. | Day 2 of each Arm | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Vaping Topography: Puff Number | Vaping topography measures will be obtained from self-reported participant vaping log during the ad libitum sessions and measured as puffs per minute. | Days 1-3 of each Arm | 
| Vaping Topography: Puff Duration | Vaping topography measures will be obtained from self-reported participant vaping log during the ad libitum sessions and measured as seconds per puff. | Days 1-3 of each Arm | 
| Vaping Topography: Inter-Puff Interval | Vaping topography measures will be obtained from self-reported participant vaping log during the ad libitum sessions and measured as seconds/minutes between puffs. | Days 1-3 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, E-Liquid