NicotineNCT07348224
Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine and Nicotine Analogues
A study testing Vaping of synthetic S-nicotine, Vaping of racemic nicotine (S-/R-nicotine) and Vaping of 6-methylnicotine in people with Nicotine and Vaping, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Nicotine, Vaping, Synthetic Nicotine
- What is being tested?
- Vaping of synthetic S-nicotine, Vaping of racemic nicotine (S-/R-nicotine) and Vaping of 6-methylnicotine
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 24 participants
- Where
- 1 siteSwitzerland
- Study dates
- 5 Aug 2026to 31 Dec 2026
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Show all 12Show fewer
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Switzerland1 site, 1 recruiting
- Recruiting
Inselspital
Bern
Evangelia Liakoni, Prof., +41 31 632 54 61, evangelia.liakoni@insel.ch
About this study
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.
Read the 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.
- Conditions
- Nicotine, Vaping, Synthetic Nicotine, Nicotine Analogues
- Being tested
- Vaping of synthetic S-nicotine, Vaping of racemic nicotine (S-/R-nicotine), Vaping of 6-methylnicotine
- Keywords
- synthetic nicotine, nicotine analogues, vaping
- Medical subject headings
- Vaping
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Vaping of synthetic S-nicotineOther
Vaping of e-liquids containing synthetic S-nicotine
Vaping of racemic nicotine (S-/R-nicotine)Other
Vaping of e-liquids containing synthetic racemic nicotine (S-/R-nicotine)
Vaping of 6-methylnicotineOther
Vaping of e-liquids containing the nicotine analogue 6-methylnicotine (6MN)
| Study group | Role | What they receive |
|---|---|---|
| Synthetic S-Nicotine | Other | Vaping of e-liquids contanining synthetic S-nicotine Receives: Other: Vaping of synthetic S-nicotine |
| Racemic nicotine (S-/R-nicotine) | Other | Vaping of e-liquids contanining synthetic racemic nicotine (containing both the S- and R-nicotine enantiomers) Receives: Other: Vaping of racemic nicotine (S-/R-nicotine) |
| 6-methylnicotine | Other | Vaping of e-liquids contanining the nicotine analogue 6-methylnicotine (6MN) Receives: Other: Vaping of 6-methylnicotine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Maximum total nicotine concentrations (Cmax)
Comparison of the maximum total nicotine (i.e. sum of both enantiomers) in blood concentrations (Cmax) between groups
Measured: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
Secondary outcomes (23)
Maximum concentration (Cmax) of 6-methylnicotine
Maximum concentration of 6-methylnicotine in blood
Measured: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
Maximum concentration (Cmax) of 6-methylnicotine's metabolites
Maximum concentration of 6-methylnicotine's metabolites in blood
Measured: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
AUC (area under the concentration-time curve) nicotine enantiomers
Area under the concentration-time curve (AUC) of nicotine enantiomers in blood
Measured: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
AUC (area under the concentration-time curve) 6-methylnicotine
Area under the concentration-time curve (AUC) of 6-methylnicotine in blood
Measured: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
AUC (area under the concentration-time curve) 6-methylnicotine's metabolites
Area under the concentration-time curve (AUC) of 6-methylnicotine's metabolites in blood
Measured: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
Tmax (time of Cmax) nicotine enantiomers
Tmax of nicotine enantiomers in blood
Measured: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
Tmax (time of Cmax) 6-methylnicotine
Tmax of 6-methylnicotine in blood
Measured: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
Tmax (time of Cmax) 6-methylnicotine's metabolites
Tmax of 6-methylnicotine's metabolites in blood
Measured: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
T1/2 (elimination half-life) nicotine enantiomers
Elimination half-life (T1/2) of nicotine enantiomers in blood
Measured: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
T1/2 (elimination half-life) 6-methylnicotine
Elimination half-life (T1/2) of 6-methylnicotine in blood
Measured: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
T1/2 (elimination half-life) 6-methylnicotine's metabolites
Elimination half-life (T1/2) of 6-methylnicotine's metabolites in blood
Measured: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
Blood nicotine metabolite ratio (NMR)
Nicotine clearance assessed using the 3'-hydroxycotinine/cotinine ratio (i.e. nicotine metabolite ratio (NMR)
Measured: 15 minutes before vaping
Saliva nicotine metabolite ratio (NMR)
Nicotine clearance assessed using the 3'-hydroxycotinine/cotinine ratio (i.e. nicotine metabolite ratio (NMR)
Measured: At baseline
Heart rate
bpm
Measured: 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)
Blood pressure
mmHg
Measured: 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)
Modified Minnesota Nicotine Withdrawal Scale (MNWS)
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.
Measured: Baseline, 10 minutes, 1 hour and 3 hours after last puff
Tiffany Questionnaire on Smoking Urges-Brief (QSU) total (global) craving score
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).
Measured: Baseline, 10 minutes, 1 hour and 3 hours after last puff
Positive and Negative Affect Schedule (PANAS)
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).
Measured: Baseline, 10 minutes, 1 hour and 3 hours after last puff
Respiratory symptoms
Questions regarding shortness of breath, wheezing, cough, phlegm; posisble answers: yes/no
Measured: Baseline and 5 minutes after last puff
Direct effects
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).
Measured: 10 minutes post-use
Modified e-cigarette evaluation questionnaire (mCEQ)
Questionnaire asssessing subjective effects
Measured: Following 4 days ad libitum use of each product
Urinary total nicotine equivalents (TNE) concentrations
Molar sum of urinary total (parent and glucuronide) nicotine, cotinine and 3'-hydroxycotinine
Measured: Following 4 days ad libitum use of each product
Urinary volatile organic compounds (VOC) concentrations
VOC in urine
Measured: Following 4 days ad libitum use of each product
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Jan 2026
- Study start5 Aug 2026
- Primary completion31 Dec 2026 (estimated)
- Study completion31 Dec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for NicotineStudies of the same condition, open and under way.
- More trials run by Insel Gruppe AG, University Hospital BernThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind
- Who is masked
- Participant, Investigator
- Enrolment
- 24 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Insel Gruppe AG, University Hospital Bern
- Sponsor type
- University, hospital or other
- Collaborators
- Swiss Tobacco Prevention Funds
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07348224
- Sponsor's protocol ID
- BASEC-ID 2025-01893
- Status last verified
- Aug 2026
- First submitted
- 24 Nov 2025
- Last updated
- 30 Sep 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 30 Sep 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine and Nicotine Analogues
- ClinicalTrials.gov ID
- NCT07348224
- Acronym / sponsor ID
- BASEC-ID 2025-01893
- Conditions
- Nicotine, Vaping, Synthetic Nicotine, Nicotine Analogues
- Keywords
- synthetic nicotine, nicotine analogues, vaping
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 24 participants (estimated)
- Lead sponsor
- Insel Gruppe AG, University Hospital BernUniversity, hospital or other
- Collaborators
- Swiss Tobacco Prevention Funds
- Study start
- 5 Aug 2026 (actual)
- Primary completion
- 31 Dec 2026 (estimated)
- Study completion
- 31 Dec 2026 (estimated)
- First posted
- 16 Jan 2026 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Double blind (participant, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Synthetic S-Nicotine | Other | Other: Vaping of synthetic S-nicotineVaping of e-liquids contanining synthetic S-nicotine |
| Racemic nicotine (S-/R-nicotine) | Other | Other: Vaping of racemic nicotine (S-/R-nicotine)Vaping of e-liquids contanining synthetic racemic nicotine (containing both the S- and R-nicotine enantiomers) |
| 6-methylnicotine | Other | Other: Vaping of 6-methylnicotineVaping of e-liquids contanining the nicotine analogue 6-methylnicotine (6MN) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- 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
Key exclusion criteria (12 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Vaping of synthetic S-nicotineVaping of e-liquids containing synthetic S-nicotine | Other | Synthetic S-Nicotine |
| Vaping of racemic nicotine (S-/R-nicotine)Vaping of e-liquids containing synthetic racemic nicotine (S-/R-nicotine) | Other | Racemic nicotine (S-/R-nicotine) |
| Vaping of 6-methylnicotineVaping of e-liquids containing the nicotine analogue 6-methylnicotine (6MN) | Other | 6-methylnicotine |
Primary outcome
Maximum total nicotine concentrations (Cmax)
Time frame: 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
23 secondary outcomes
Maximum concentration (Cmax) of 6-methylnicotine
Time frame: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
Maximum concentration (Cmax) of 6-methylnicotine's metabolites
Time frame: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
AUC (area under the concentration-time curve) nicotine enantiomers
Time frame: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
AUC (area under the concentration-time curve) 6-methylnicotine
Time frame: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
AUC (area under the concentration-time curve) 6-methylnicotine's metabolites
Time frame: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
Tmax (time of Cmax) nicotine enantiomers
Time frame: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
Tmax (time of Cmax) 6-methylnicotine
Time frame: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
Tmax (time of Cmax) 6-methylnicotine's metabolites
Time frame: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
T1/2 (elimination half-life) nicotine enantiomers
Time frame: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
T1/2 (elimination half-life) 6-methylnicotine
Time frame: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
T1/2 (elimination half-life) 6-methylnicotine's metabolites
Time frame: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff
Blood nicotine metabolite ratio (NMR)
Time frame: 15 minutes before vaping
Saliva nicotine metabolite ratio (NMR)
Time frame: At baseline
Heart rate
Time frame: 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)
Blood pressure
Time frame: 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)
Modified Minnesota Nicotine Withdrawal Scale (MNWS)
Time frame: Baseline, 10 minutes, 1 hour and 3 hours after last puff
Tiffany Questionnaire on Smoking Urges-Brief (QSU) total (global) craving score
Time frame: Baseline, 10 minutes, 1 hour and 3 hours after last puff
Positive and Negative Affect Schedule (PANAS)
Time frame: Baseline, 10 minutes, 1 hour and 3 hours after last puff
Respiratory symptoms
Time frame: Baseline and 5 minutes after last puff
Direct effects
Time frame: 10 minutes post-use
Modified e-cigarette evaluation questionnaire (mCEQ)
Time frame: Following 4 days ad libitum use of each product
Urinary total nicotine equivalents (TNE) concentrations
Time frame: Following 4 days ad libitum use of each product
Urinary volatile organic compounds (VOC) concentrations
Time frame: Following 4 days ad libitum use of each product
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 30 Sep 2026.
- Individual participant dataSharing planned: Undecided
Related trials for Nicotine
Enrolling by invitationObservational study
Using Smartwatches to Monitor Smoking in Real-life Situations
Smoking
Not yet recruitingPhase 1/2
Acute Nicotine Gum and Auditory Brain Responses in Adults With Chronic Tinnitus
Tinnitus, Chronic Subjective Tinnitus
RecruitingPhase 3
Trial Investigating the Efficacy and Safety of Weekly Lonapegsomatropin Compared to Daily Somatropin in Children and Adolescents With Short Stature or Growth Failure Due to Growth Hormone Sufficient Disorders
Turner Syndrome, Short Stature Homeobox Gene Mutation
RecruitingObservational study
Longitudinal Prospective Study of Maternal and Child Nutrition in Arkansas
Maternal Nutrition, Infant Nutrition
Recruiting
Young Adult Tobacco/Nicotine and Cannabis Co-use
Tobacco Use Disorder, Nicotine Dependence
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Vaping of synthetic S-nicotine, Vaping of racemic nicotine (S-/R-nicotine) and Vaping of 6-methylnicotine in people with Nicotine and Vaping, run by Insel Gruppe AG, University Hospital Bern at 1 site in Switzerland.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 5 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 30 Sep 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Switzerland. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Evangelia Liakoni, Prof. (+41 31 632 54 61, evangelia.liakoni@insel.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Maximum total nicotine concentrations (Cmax) (time frame: 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 30 Sep 2026.