Nicotine Dependence
Conditions
Keywords
nicotine, pharmacokinetics, pharmacodynamics
Brief summary
Comparison of the pharmacokinetics and pharmacodynamics of two different nicotine salt concentrations and free-base nicotine using an open vape pod system
Detailed description
On each study day, one puff will be taken with the assigned product every 30 seconds (total of 10 puffs). Blood samples will be collected to measure nicotine 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff. Heart rate and blood pressure will be measured 15 minutes before and 2, 10, 15, 30, 60, 120, and 180 minutes after the last puff. Post-use withdrawal, craving, reward, and satisfaction will be assessed 10 minutes and 1 and 3 hours after the last puff using the modified Minnesota Nicotine Withdrawal Scale (MNWS), the Tiffany Questionnaire on Smoking Urges (QSU), and the Positive and Negative Affect Schedule (PANAS) questionnaires. Respiratory symptoms will be assessed at baseline and 5 minutes after the last puff. Ten minutes post-use, the direct effects of the assigned product (e.g. satisfying, calming, pleasant, vape another one right now) will also be assessed using visual analog scales.
Interventions
OTHERstandardized vaping protocol
The following questionnaires will first be completed: Modified Minnesota Nicotine Withdrawal Scale, Tiffany Questionnaire on Smoking Urges-Brief total (global) craving score, Positive and Negative Affect Schedule. The assigned product will then be given to the participant, and one puff will be taken every 30 seconds (total of 10 puffs). Blood samples will be collected 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff. Heart rate and blood pressure will be measured 15 minutes before and 2, 10, 15, 30, 60, 120, and 180 minutes after the last puff. Post-use withdrawal, craving, reward, and satisfaction will be assessed 10 minutes and 1 and 3 hours after the last puff. Respiratory Symptoms will be assessed at baseline and 5 minutes after the last puff. Ten minutes post-use, the direct effects will also be assessed.
Sponsors
University of Bern
Insel Gruppe AG, University Hospital Bern
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
Masking description
Vaping of high and low concentration nicotine salt and free-base nicotine will be double-blinded.
Intervention model description
Participants will be switched in a within-subject crossover design among the three product types.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
Yes
Inclusion criteria
* Men or women, age 18 or older at screening, who have used electronic cigarettes and/or smoked at least 5 cigarettes per day in the past 30 days * Saliva cotinine of \> 50 ng/mL at screening * No clinically significant findings on the physical examination at screening * Ability to communicate well with the investigator and to understand and comply with the requirements of the study * Women of child-bearing age: willingness of using a reliable contraception method during the study * Signed informed consent
Exclusion criteria
* Known hypersensitivity/allergy to a content of the e-liquid * Pregnancy or breast feeding * BMI \< 18 or \> 28 kg/m2 at screening * History or clinical evidence of alcoholism or drug abuse within the 3-year period prior to screening * Loss of ≥ 250 ml of blood within 3 months prior to screening, including blood donation * Treatment with an investigational drug within 30 days prior to screening * Treatment with prescribed or over-the-counter (OTC) medications with potential influence on CYP2A6 function within 1 week prior to screening (with the exception of contraception) * History or clinical evidence of any disease (e.g. gastrointestinal tract-disease) and/or existence of any surgical or medical condition, which in the opinion of the investigator might interfere with the absorption, distribution, metabolism or excretion of the study drugs, or which might increase the risk for toxicity * Legal incapacity or limited legal capacity at screening * Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nicotine Peak Plasma Concentration (Cmax) | Blood samples collection: 15 minutes before and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff | Comparison of nicotine Cmax between groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Time at which the Cmax is observed (Tmax) | Blood samples collection: 15 minutes before and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff | Comparison of the nicotine Tmax between groups |
| Elimination half-life (t1/2) | Blood samples collection: 15 minutes before and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff | Comparison of t1/2 between groups |
| Genotyping of the hepatic cytochrome P450 enzyme CYP2A6 | Blood sample collection during first session | CYP2A6 genotype (allele variants) |
| Nicotine metabolite ratio (NMR) | Assessed at screening visit | Nicotine clearance assessed using 3'-hydroxycotinine/cotinine ratios |
| Modified Minnesota Nicotine Withdrawal Scale (MNWS) | Baseline, 10 minutes and 1 and 3 hours after the last puff | Excluding items relating to sleep disturbance and constipation, including eight items (angry/irritable/frustrated, anxious/nervous, depressed mood/sad, desire or craving to smoke, difficulty concentrating, increased appetite/hungry, restless and impatient), rated on a 0=none to 4=severe scale |
| Tiffany Questionnaire on Smoking Urges-Brief (QSU) total (global) craving score | Baseline, 10 minutes and 1 and 3 hours after the last puff | Mean of ten items, rated on a 1=strongly disagree to 7=strongly agree scale |
| Area under the plasma concentration versus time curve (AUC) | Blood samples collection: 15 minutes before and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff | Comparison of the nicotine AUC between groups |
| Respiratory symptoms | At baseline and 5 minutes after the last puff | Yes/no: shortness of breath, wheezing, cough, phlegm |
| Direct effects | Ten minutes post-use | E.g. satisfying, calming, pleasant, vape another one right now, assessed using visual analog scales (0-100 mm) with a single word scored from left (not at all) to right (extremely) |
| Heart rate | 15 minutes before and 2, 10, 15, 30, 60, 120, and 180 minutes after the last puff | Heart rate measurements (bpm) |
| Systolic blood pressure | 15 minutes before and 2, 10, 15, 30, 60, 120, and 180 minutes after the last puff | Systolic blood pressure measurements (mmHg) |
| Diastolic blood pressure | 15 minutes before and 2, 10, 15, 30, 60, 120, and 180 minutes after the last puff | Diastolic blood pressure measurements (mmHg) |
| Positive and Negative Affect Schedule (PANAS) | Baseline, 10 minutes and 1 and 3 hours after the last puff | Including items assigned as Positive or Negative Affect (each score is the sum of ten items, rated on a 1=very slightly/not at all to 5=extremely scale) |
Countries
Switzerland
Outcome results
None listed