Pharmacokinetics and Pharmacodynamics of Synthetic Nicotine and Nicotine Analogues
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 24
- 试验地点
- 2
- 主要终点
- Maximum total nicotine concentrations (Cmax)
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Other
- 盲法
- Double (Participant, Investigator)
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •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
排除标准
- •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
研究组 & 干预措施
6-methylnicotine
Vaping of e-liquids contanining the nicotine analogue 6-methylnicotine (6MN)
干预措施: Vaping of 6-methylnicotine (Other)
Synthetic S-Nicotine
Vaping of e-liquids contanining synthetic S-nicotine
干预措施: Vaping of synthetic S-nicotine (Other)
Racemic nicotine (S-/R-nicotine)
Vaping of e-liquids contanining synthetic racemic nicotine (containing both the S- and R-nicotine enantiomers)
干预措施: Vaping of racemic nicotine (S-/R-nicotine) (Other)
结局指标
主要结局
Maximum total nicotine concentrations (Cmax)
时间窗: 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
次要结局
- 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 (Cmax) of 6-methylnicotine's metabolites(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(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(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(15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff)
- 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 (time of Cmax) 6-methylnicotine(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(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(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(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(15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff)
- Blood nicotine metabolite ratio (NMR)(15 minutes before vaping)
- Saliva nicotine metabolite ratio (NMR)(At baseline)
- Blood steroid hormone levels(At baseline, 15 minutes before vaping and 2, 5, 15, 30, 60, 120, and 180 minutes after the last puff during the first part of the study and following 4 days ad libitum use during the second part)
- Saliva steroid hormone levels(At baseline)
- Urine steroid hormone levels(At baseline and following 4 days ad libitum use of each product)
- 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))
- 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))
- Modified Minnesota Nicotine Withdrawal Scale (MNWS)(Baseline, 10 minutes, 1 hour and 3 hours after last puff)
- Tiffany Questionnaire on Smoking Urges-Brief (QSU) total (global) craving score(Baseline, 10 minutes, 1 hour and 3 hours after last puff)
- Positive and Negative Affect Schedule (PANAS)(Baseline, 10 minutes, 1 hour and 3 hours after last puff)
- Respiratory symptoms(Baseline and 5 minutes after last puff)
- Direct effects(10 minutes post-use)
- Modified e-cigarette evaluation questionnaire (mCEQ)(Following 4 days ad libitum use of each product)
- Urinary total nicotine equivalents (TNE) concentrations(Following 4 days ad libitum use of each product)
- Urinary volatile organic compounds (VOC) concentrations(Following 4 days ad libitum use of each product)