Evaluating the Comparative Pharmacokinetics of Nicotine After Administration Via JUUL or Tobacco Cigarettes

Study Overview
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Brief Summary
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This is an observational, crossover design that will examine the pharmacokinetics and pharmacodynamics of impact of smoking tobacco cigarettes or vaping the JUUL electronic cigarette.

Detailed Description
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The goal of this study is to better understand the pharmacokinetic and pharmacodynamics responses produced by the JUUL e-cigarette, compared to tobacco cigarettes, in e-cigarette and tobacco cigarette smokers. Specific Aim #1- To categorize the nicotine pharmacokinetic (PK) profile (maximum plasma concentration; time to maximum plasma concentration and area under the concentration-time curve) and compare when using the JUUL e-cigarette vs. a tobacco cigarette in a standardized manner. Specific Aim #2- To categorize the nicotine PK profile (maximum plasma concentration; time to maximum plasma concentration and area under the concentration-time curve(AUC)) and compare when using the JUUL e-cigarette vs a tobacco cigarette when using the product ad libitum. Specific Aim #3- To evaluate various outcomes following JUUL e-cigarette or tobacco cigarette use, both with standardized and ad lib use including: heart rate, plasma catecholamines, pulmonary function testing. Specific Aim #4- To evaluate and compare the effects on craving, reward and satisfaction when using the JUUL e-cigarette vs. tobacco cigarette.

Official Title
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Evaluating the Comparative Pharmacokinetics of Nicotine After Administration Via JUUL or Tobacco Cigarettes

Conditions
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E-cigarettes, Nicotine Administration & Dosage, Vaping, E-Liquid, Tobacco Smoking

Intervention / Treatment
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* Other: JUUL
* Other: Tobacco


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) - - Considered out of range if both machine and manual readings are above/below these thresholds. - Systolic Blood Pressure < 160 and > 90* - Diastolic Blood Pressure < 100 and > 50* Age: >= 21 & <=70 years old Body Mass Index (BMI) <= 38.0 (at PI's discretion for higher BMI if no other concurrent health issues) Willingness to avoid combusted marijuana up to 48 hours before each study visit Nicotine strength of e-liquid of usual e-cigarette > 0 mg/ml Group 1 Experienced E-cigarette users - Current use of tobacco cigarettes (<5 cigarettes per day) - Current e-cigarette use at least 15 days out of the past 30 days of a non-mod e-cigarette Group 2 Primary Tobacco cigarette users: - Currently smoking >= 5 cigarettes per day - Current e-cigarette use must be < 5 times per month Saliva cotinine >=50 ng/ml or urine cotinine and/or NicAlert=6 Must have a smart phone, computer, or tablet and internet access (for remote procedures) 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 principal investigator (PI) and/or medical monitor and considered for inclusion - History of psychiatric hospitalizations are not exclusionary, but study participation will be determined as per PI's or medical monitor'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 (Tetrahydrocannabinol (THC) & prescribed medications okay) - Opioid replacement therapy (including methadone, buprenorphine, or other) Psychiatric medications - Current regular use of any psychiatric medications is exclusionary, with the exception of Selective Serotonin Reuptake Inhibitor (SSRI) and serotonin-norepinephrine reuptake Inhibitor (SNRI) and current evaluation by the PI and/or medical monitor that the participant is otherwise healthy, stable, and able to participate Medications - Use of sympatholytic medications for cardiovascular conditions including hypertension (Example: beta and alpha-blockers) - Use of medications that are inducers of nicotine metabolizing enzyme CYP2A6 (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 Other Tobacco Products (OTP) - Any of the following products in combination more than 15 times in the past month - - smokeless tobacco (snus, oral snuff, chewing tobacco) - - pipes - - cigars, cigarillos, little cigars - - blunts, spliffs - - hookah Other/Misc. Chronic Health Conditions Fainting (within the last 30 days) Other life threatening illnesses as per PI's or medical monitor's discretion Pregnancy - Pregnancy (self-reported and urine pregnancy test) - Breastfeeding (determined by self-report) Concurrent participation in another clinical trial (at PI's discretion) Inability to read and write in English Planning to quit smoking or vaping within the next 60 days Recent onset or change (worsening) in cough, fever and/or abdominal symptoms (vomiting or pain) in the past two weeks Diagnosis of pneumonia in the past 3 months Uncomfortable with blood draws Known allergy to propylene glycol or vegetable glycerin

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 |
| --- | --- |
| Experimental: Electronic Cigarette<br>The participants will participate in a standardized vaping session using a JUUL E-cigarette device with a JUUL e-liquid pod. | Other: JUUL<br>* Electronic Cigarette<br>|
| Experimental: Tobacco Cigarette<br>The participants will participate in a standardized smoking session using commercial tobacco cigarettes. | Other: Tobacco<br>* Tobacco Cigarette<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Nicotine Exposure | Plasma nicotine area under the concentrated time curve (AUC) (ng/ml*h) | Plasma collected at baseline (prior to any product use) and at 2, 5, 7, 10, 15, 30, 60, 90, and 118 minutes after end of standardized session. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Overall Mean Heart Rate Over Time | Participant heart rate will be measured in beats per minute (bpm) at baseline (before any use of products) and at 2, 5, 7, 10, 15, 30, 45, 60, 75, 90, 100,and 118 minutes after the standardized sessions of e-cigarette and tobacco cigarette use. The mean of each time point will be averaged over time. | Up to 118 minutes after end of standardized session. | 
| Mean Systolic Blood Pressure Over Time | Participant systolic blood pressure will be taken at Baseline (prior to use of any product) and at 5, 10, 15, 30, 45, 60, 75, 90, 100, and 118 minutes after the standardized sessions of e-cigarette and/or tobacco cigarette use on each arm. The mean of each time point will be averaged over time. | Up to 118 minutes after end of standardized session. | 
| Mean Diastolic Blood Pressure Over Time | Participant diastolic blood pressure will be taken at Baseline (prior to use of any product) and at 5, 10, 15, 30, 45, 60, 75, 90, 100, and 118 minutes after the standardized session during e-cigarette and/or tobacco cigarette use on each arm. The mean of each time point will be averaged over time. | Up to 118 minutes after end of standardized session. | 
| Mean Questionnaire of Smoking Urges (QSU) and Modified for E-cigarettes (mQSU) Score Over Time | The QSU (Questionnaire of Smoking Urges) is a self-report survey, modified to replace cigarette with e-cigarette and smoking with vaping for use during both the tobacco cigarette and the E-cigarette Arm. This instrument is composed of 10 items; 5 items measuring desire/intention to smoke/vape with smoking/vaping perceived as rewarding (Factor 1), and 5 items measuring anticipation of relief from negative affect with an urgent desire to smoke/vape (Factor 2). Scores for each factor (1 and 2) range from 5-35 with higher scores indicating more severe craving. The mean and standard deviation will be reported. | Up to 118 minutes after end of standardized session | 
| Mean Minnesota Nicotine Withdrawal Scale (MNWS) Score Over Time | The Minnesota Nicotine Withdrawal Scale is an 15-item self -report scale designed to measure the severity of craving and withdrawal symptoms experienced during smoking cessation. Each item is on a scale of 0 to 4 with 0=none to 4=Severe. The responses to each item are summed to produce a total withdrawal summary score with a possible range between 0 and 60, with higher scores indicating greater withdrawal symptom severity with greater scores indicating a higher level of severity in nicotine withdrawal symptoms overall. The mean and standard deviation will be reported. | Up to 118 minutes after end of standardized session. | 
| Mean Cigarette Evaluation Scale (CES) and Modified for E-cigarettes (mCES) Score Over Time | The CES is a self-report survey measuring smoking/vaping satisfaction, psychological reward, aversion, sensations, and craving reduction. This 12-item instrument has a total score range from 12 to 84, with higher scores indicating higher perception of the above factors. The mean and standard deviation will be reported. | Up to 240 minutes after end of standardized session |