Nicotine, Nicotine Analogues, Synthetic Nicotine, Vaping
Conditions
Keywords
synthetic nicotine, nicotine analogues, vaping
Brief summary
Electronic cigarettes are battery-operated devices that can produce an aerosol by heating a liquid which commonly contains nicotine. In recent years, products containing synthetically produced nicotine and nicotine analogues have entered the market. However, it remains unclear whether these types of nicotine have the same effects as conventional nicotine derived from the tobacco plant. The aim of this study is to investigate the effects of these nicotine types and to gain a better understanding of their respective mechanisms of action.
Detailed description
In the first part of the study, participants will use electronic cigarettes containing synthetic nicotine or nicotine analogs at three sessions in the hospital, following a specific schedule. In the second part, each product will be used for four days outside the hospital. The study is double-blind, meaning neither the participants nor the study team will know which product is being used. The study comprises a total of seven appointments at the hospital. During these appointments, participants will be asked questions about their electronic cigarette and tobacco use, and samples of saliva, urine, and blood will be collected.
Interventions
OTHERVaping of synthetic S-nicotine
Vaping of e-liquids containing synthetic S-nicotine
OTHERVaping of racemic nicotine (S-/R-nicotine)
Vaping of e-liquids containing synthetic racemic nicotine (S-/R-nicotine)
OTHERVaping of 6-methylnicotine
Vaping of e-liquids containing the nicotine analogue 6-methylnicotine (6MN)
Sponsors
Insel Gruppe AG, University Hospital Bern
Swiss Tobacco Prevention Funds
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
OTHER
Masking
DOUBLE (Subject, Investigator)
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 EC with nicotine during at least 10 of the past 30 days * Saliva cotinine concentration of \> 30 ng/mL 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 engaging in sexual activities which can lead to pregnancy: willingness of using a reliable/hormonal contraception method during the study (hormonal, e.g. pill, intrauterine devices, or mechanical method, e.g. condom, diaphragm) * Signed informed consent form
Exclusion criteria
* Known hypersensitivity/allergy to a content of the e-liquids * Smoking of more than 5 cigarettes per day in the past 30 days * Pregnant or lactating women * Intention to become pregnant during the course of the study * BMI \< 18 or \> 30 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 medications with known 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 of 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 |
|---|---|---|
| Maximum total nicotine concentrations (Cmax) | 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff | Comparison of the maximum total nicotine (i.e. sum of both enantiomers) in blood concentrations (Cmax) between groups |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Maximum concentration (Cmax) of 6-methylnicotine | 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff | Maximum concentration of 6-methylnicotine in blood |
| Maximum concentration (Cmax) of 6-methylnicotine's metabolites | 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff | Maximum concentration of 6-methylnicotine's metabolites in blood |
| AUC (area under the concentration-time curve) nicotine enantiomers | 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff | Area under the concentration-time curve (AUC) of nicotine enantiomers in blood |
| AUC (area under the concentration-time curve) 6-methylnicotine | 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff | Area under the concentration-time curve (AUC) of 6-methylnicotine in blood |
| AUC (area under the concentration-time curve) 6-methylnicotine's metabolites | 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff | Area under the concentration-time curve (AUC) of 6-methylnicotine's metabolites in blood |
| Tmax (time of Cmax) nicotine enantiomers | 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff | Tmax of nicotine enantiomers in blood |
| Tmax (time of Cmax) 6-methylnicotine | 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff | Tmax of 6-methylnicotine in blood |
| Tmax (time of Cmax) 6-methylnicotine's metabolites | 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff | Tmax of 6-methylnicotine's metabolites in blood |
| T1/2 (elimination half-life) nicotine enantiomers | 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff | Elimination half-life (T1/2) of nicotine enantiomers in blood |
| T1/2 (elimination half-life) 6-methylnicotine | 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff | Elimination half-life (T1/2) of 6-methylnicotine in blood |
| T1/2 (elimination half-life) 6-methylnicotine's metabolites | 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff | Elimination half-life (T1/2) of 6-methylnicotine's metabolites in blood |
| Blood nicotine metabolite ratio (NMR) | 15 minutes before vaping | Nicotine clearance assessed using the 3'-hydroxycotinine/cotinine ratio (i.e. nicotine metabolite ratio (NMR) |
| Saliva nicotine metabolite ratio (NMR) | At baseline | Nicotine clearance assessed using the 3'-hydroxycotinine/cotinine ratio (i.e. nicotine metabolite ratio (NMR) |
| Heart rate | Baseline, 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff, at study completion (2.5-6.5 weeks after screening) | bpm |
| Blood pressure | Baseline, 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff, at study completion (2.5-6.5 weeks after screening) | mmHg |
| Modified Minnesota Nicotine Withdrawal Scale (MNWS) | Baseline, 10 minutes, 1 hour and 3 hours after last puff | Score/questionnaire asssessing withdrawal: The Modified Minnesota Nicotine Withdrawal Scale (MNWS) (excluding items related 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, 1 hour and 3 hours after last puff | Score/questionnaire asssessing craving: The Tiffany Questionnaire on Smoking Urges-Brief (QSU) total (global) craving score as the average of all responses (mean of ten items, rated on a 1=strongly disagree to 7=strongly agree scale). |
| Positive and Negative Affect Schedule (PANAS) | Baseline, 10 minutes, 1 hour and 3 hours after last puff | Score/questionnaire asssessing satisfaction: The Positive and Negative Affect Schedule (PANAS) 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). |
| Respiratory symptoms | Baseline and 5 minutes after last puff | Questions regarding shortness of breath, wheezing, cough, phlegm; posisble answers: yes/no |
| Direct effects | 10 minutes post-use | Questions regarding e.g. satisfying, calming, pleasant, vape another one right now, using visual analog scales (0-100 mm) with a single word scored from left (not at all) to right (extremely). |
| Modified e-cigarette evaluation questionnaire (mCEQ) | Following 4 days ad libitum use of each product | Questionnaire asssessing subjective effects |
| Urinary total nicotine equivalents (TNE) concentrations | Following 4 days ad libitum use of each product | Molar sum of urinary total (parent and glucuronide) nicotine, cotinine and 3'-hydroxycotinine |
| Urinary volatile organic compounds (VOC) concentrations | Following 4 days ad libitum use of each product | VOC in urine |
Countries
Switzerland
Contacts
CONTACTEvangelia Liakoni, Prof.
Outcome results
None listed