Pharmacokinetics and Pharmacodynamics of Nicotine With Use of Standardized Research Electronic Cigarette (SREC)

Study Overview
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Brief Summary
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This is a crossover study that will examine use behaviors, chemical exposures, and biological effects of Standardized Research Electronic Cigarette (SREC) compared to usual brand e-cigarette use in natural or synthetic nicotine users.

Detailed Description
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OBJECTIVES: I. To characterize nicotine delivery, systemic exposure and effects from SREC in comparison with usual to usual nicotine brand use. II. To assess aspects of harm of SREC use compared to usual nicotine brand use. OUTLINE: Eligible participants will be assigned to one of two treatment conditions for the initial assessment which will take place in a hospital setting. The participant will then be assigned to the second condition within 2 weeks after the initial assessment which will also take place in a hospital setting to repeat the same procedures.

Official Title
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Comparative Pharmacokinetics and Pharmacodynamics of Nicotine With Use of NIDA Standardized Research Electronic Cigarette (SREC) vs Usual Brand E-cigarette

Conditions
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Nicotine Dependence, Tobacco Toxicity, Cardiovascular Risk Factors

Intervention / Treatment
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* Other: Standardized Research E-Cigarette (SREC)
* Other: Over the Counter E-Cigarette (EC)
* Behavioral: Biological Samples
* Other: Smoking-related Questionnaires


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- 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. Body Mass Index <= 38.0. Current regular user of electronic cigarettes (EC) EC device use at least 15 or more days in the past 30 days (with e- liquid >= 3mg/ml) No restriction on flavor or type of e-cigarette used Saliva cotinine >= 50 ng/ml and/or NicAlert = 6 Age >= 21 years old <= 70 years old Willingness to abstain from drug use for the duration of the study Exclusion Criteria: The following unstable medical conditions: 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) 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 (Example: nicotine patch, lozenge, gum). Any stimulant medications (example: Adderall) generally given for attention deficit hyperactivity disorder (ADHD) treatment. Other/Misc. Health Conditions Oral thrush Fainting (within the last 30 days) Other life threatening illnesses as per principal investigator and/or study physician's discretion Pregnancy Pregnancy (self-reported and urine pregnancy test) Breastfeeding (determined by self-report) Women of childbearing potential must be using an acceptable method of contraception Concurrent participation in another clinical trial. Inability to read and write in English Planning to quit smoking or vaping within the next 60 days A known propylene glycol/vegetable glycerin allergy Uncomfortable with getting blood drawn Recent onset or change (worsening) in cough, fever and/or abdominal symptoms (vomiting or pain) in the past two weeks

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: Participants will be randomized to the starting condition using a Latin square design
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Usual Brand E-Cigarette (EC) then SREC<br>Participants will be admitted to hospital research ward within 32 hours of the orientation visit and begin a standardized session of product use using the usual brand of e-cigarette that participants utilize for nicotine use, and will provide expired carbon dioxide samples, pharmacokinetic (PK) blood samples, urine samples, and have cardiovascular and vital signs monitored. Participants will also be asked to complete nicotine-related questionnaires. Participants will then return within 2 weeks to repeat the procedures using the SREC. | Other: Standardized Research E-Cigarette (SREC)<br>* Standardized Research E-Cigarette (SREC) will be obtained through NJOY, LLC and provided at the hospital stay.<br>Other: Over the Counter E-Cigarette (EC)<br>* Usual brand e-cigarettes will be provided at the hospital stay.<br>* Other names: Usual Brand E-Cigarette (EC);Behavioral: Biological Samples<br>* Blood, urine, and expired carbon dioxide will be obtained during the course of the study.<br>* Other names: Biological Specimens;Other: Smoking-related Questionnaires<br>* Nicotine and Smoking behavior and dependence questionnaires will be administered at screening, before and during hospital stays.<br>* Other names: Behavioral Questionnaires;|
| Experimental: SREC then Usual Brand E-Cigarette (EC)<br>Participants will be admitted to hospital research ward within 32 hours of the orientation visit and begin a standardized session of product use using the SREC, and will provide expired carbon dioxide samples, pharmacokinetic (PK) blood samples, urine samples, and have cardiovascular and vital signs monitored. Participants will also be asked to complete nicotine-related questionnaires. Participants will then return within 2 weeks to repeat the procedures using the usual brand of e-cigarette that participants utilize for nicotine use. | Other: Standardized Research E-Cigarette (SREC)<br>* Standardized Research E-Cigarette (SREC) will be obtained through NJOY, LLC and provided at the hospital stay.<br>Other: Over the Counter E-Cigarette (EC)<br>* Usual brand e-cigarettes will be provided at the hospital stay.<br>* Other names: Usual Brand E-Cigarette (EC);Behavioral: Biological Samples<br>* Blood, urine, and expired carbon dioxide will be obtained during the course of the study.<br>* Other names: Biological Specimens;Other: Smoking-related Questionnaires<br>* Nicotine and Smoking behavior and dependence questionnaires will be administered at screening, before and during hospital stays.<br>* Other names: Behavioral Questionnaires;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean Peak Nicotine Concentration | The investigators will compare peak nicotine concentrations between SREC vs. EC use | Collected 2, 5, 7, 10, 15, 30, 45, 60, 75, 90, and 120 minutes post end vaping session | 
| Mean Time of Peak Nicotine Concentration | Compare peak nicotine concentration between SREC vs. EC use. | Collected 2, 5, 7, 10, 15, 30, 45, 60, 75, 90, and 120 minutes post end vaping session | 
| Area Under the plasma nicotine concentration-time Curve (AUC) at 120 minutes | Compare peak nicotine concentration between SREC vs. EC | Collected 2, 5, 7, 10, 15, 30, 45, 60, 75, 90, and 120 minutes post end vaping session | 
| Mean overall systemic nicotine exposure | Descriptive statistics will be used to examine systemic nicotine exposure from use of SREC and compare to EC | during the 3 hr of ad libitum use | 
| Mean inter-puff interval | The patterns of SREC puffing and EC use will be examined looking at the average and variability (SD) of inter-puff interval during the 3 hr of ad libitum use. | during the 3 hr of ad libitum use | 
| Change in Mean score on the Modified Cigarette Evaluation Questionnaire (mCEQ) | The mCEQ use three multi-item domains (subscales) and two single items: Smoking Satisfaction, Psychological Reward, Aversion, Enjoyment of Respiratory Tract Sensations and Craving Reduction. Scores for each subscale are calculated as the average of its individual item responses of The items are rated on a seven-point scale ranging from 1 (not at all) to 7 (extremely). Higher scores indicate greater intensity of each smoking effect with, for example, greater satisfaction or psychological reward after smoking. Scores will be compared between SREC and EC use. | Up to 1 month | 
| Change in Mean score on the Minnesota Tobacco Withdrawal Scale-Revised (MTWS-R) | The MTWS-R features two separate measures for examining the severity of nicotine withdrawal symptoms in a participant: a self-report scale and an observer scale. The observer scale asks the scale-taker to rate the severity of four symptoms in someone the they know who is experiencing nicotine withdrawal: angry/irritable/frustrated, anxious/tense, depressed, and restless/impatient. The self-report version asks for rankings of the severity of those same four symptoms, plus eleven others that cannot be observed by outsiders (including such things as desire or craving to smoke, insomnia, sleep problems, awakening at night, or dizziness). Both scales use a Likert-type scale for the severity ratings, ranging from 0 (not at all) to 4 (severe). These scores are tallied to calculate an a total withdrawal discomfort score and will be compared between SREC and EC use | Up to 1 month | 
| Change in Mean score on the Questionnaire on Smoking Urges (QSU-Brief) | The QSU-Brief consists of 10 statements about the respondent's feelings and thoughts about the participants desire to smoke cigarettes as the participant is completing the questionnaire (i.e., right now). Each response is scored a number ranging from 1 (strongly disagree) to 7 (strongly agree) and total scores are calculated by summing the item scores to compare craving between SREC and EC use | Up to 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Mean acrolein levels within participants | Urine excretion of mercapturic acid metabolites of volatile organic compounds (VOCs), with a particular focus on acrolein will be measured and compared between SREC and EC use | Up to 1 month | 
| Mean propylene oxide levels within participants | Urine excretion of mercapturic acid metabolites of VOCs, with a particular focus on propylene oxide will be measured and compared between SREC and EC use | Up to 1 month | 
| Median benzene levels within participants | Urine excretion of mercapturic acid metabolites of VOCs, with a particular focus on benzene will be measured and compared between SREC and EC use | Up to 1 month | 
| Mean heart rate within participants | The cardiovascular effects of e-cigarette use as measured by heart rate will be compared between SREC and EC use | Up to 1 month | 
| Mean blood pressure (both systolic and diastolic) within participants | The cardiovascular effects of e-cigarette use as measured by blood pressure will be compared between SREC and EC use | Up to 1 month | 
| Mean plasma epinephrine within participants | The cardiovascular effects of e-cigarette use as measured by plasma epinephrine will be compared between SREC and EC use | Up to 1 month | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Nicotine Pharmacokinetics, Nicotine Pharmacodynamics, Electronic Cigarettes, E-Cigarettes