Concentration Impact Nicotine Salt

Study Overview
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Brief Summary
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Double-blind (for the two active arms), randomized, three-arm (two active and one control) clinical trial investigating factors (e.g. nicotine concentration) influencing the success of smoking cessation strategies and possible health risks related to nicotine salt vaping.

Detailed Description
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At the clinic screening visit demographics, smoking (including the Fagerström Test for Cigarette Dependence (FTCD) Questionnaire) and medical history, concomitant medication, vital signs, body mass index (BMI) and exhaled carbon monoxide (CO) will be assessed, and a physical examination will be performed. Saliva samples will be collected for cotinine and nicotine metabolite ratio (NMR) measurement, urine samples for urinary anabasine, 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanol (NNAL), nicotine metabolites, tobacco-specific nitrosamines (TSNA), and VOC, and blood samples for genotyping, steroid levels, blood lipids, creatinine, and glucose. After randomization the open system vape device and the nicotine salt e-liquids will be distributed to the participants of the two active arms. Use of e-liquids in the active arms will be ad libitum during three months and will be monitored by returned empty e-liquid bottles. All groups will receive smoking cessation counseling at baseline, week 1, and week 4. Visits at the center at baseline, week 4, and 3 months will include questionnaires regarding TC and EC use, respiratory symptoms, liking, and adverse events, measurement of heart rate, blood pressure, BMI, blood steroid levels, HDL, LDL, creatinine and glucose, and measurement of urinary TSNA, VOC and nicotine metabolites. For participants self-reporting TC abstinence, exhaled CO validation and urinary anabasine and NNAL will be collected to verify tobacco abstinence. A follow-up visit also assessing TC abstinence will take place at 6 months.

Official Title
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Impact of the Nicotine Concentration on the Efficacy of a Nicotine Salt Vape Pod System as Smoking Cessation Tool

Conditions
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Smoking Cessation, Vaping

Intervention / Treatment
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* Procedure: Smoking cessation counseling
* Other: Open system vape device and nicotine salt e-liquids


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult (≥ 18 years old) smokers (at least 5 TC per day for at least 12 months) Motivated to quit smoking as evidenced by signing the informed consent form at trial enrolment specifying that a target quit date will be set Exhaled CO ≥ 10 ppm or saliva cotinine of > 30 ng/ml (in case of borderline CO measurement of 6-10 ppm) at screening Willing to participate in the trial even if allocated to the control group Ability to communicate well with the investigator and to understand and comply with the requirements of the study Signed informed consent form Exclusion Criteria: Known hypersensitivity/allergy to a content of the e-liquid Pregnancy or breast feeding Intention to become pregnant during the course of the study Current regular use of EC or tobacco heating systems Use of NRT, varenicline, or bupropion in the month prior to the screening visit People who smoke tobacco combined with marijuana and do not currently want to quit marijuana use Participation in an interventional trial within 30 days prior to the screening visit 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

Ages Eligible for Study
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Minimum Age: 18 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active arm, low concentration (18 mg/mL) nicotine salt e-liquids<br> | Procedure: Smoking cessation counseling<br>* Smoking cessation counseling at baseline, week 1, and week 4.<br>Other: Open system vape device and nicotine salt e-liquids<br>* Ad libitum use of nicotine salt e-liquids during three months.<br>|
| Active Comparator: Active arm, high concentration (59 mg/mL) nicotine salt e-liquids<br> | Procedure: Smoking cessation counseling<br>* Smoking cessation counseling at baseline, week 1, and week 4.<br>Other: Open system vape device and nicotine salt e-liquids<br>* Ad libitum use of nicotine salt e-liquids during three months.<br>|
| Other: Control group<br>Receive only smoking cessation counseling | Procedure: Smoking cessation counseling<br>* Smoking cessation counseling at baseline, week 1, and week 4.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-day point prevalence tobacco abstinence (in terms of non-inferiority) | Defined as no smoking, i.e. not a puff, self-reported and confirmed by exhaled carbon monoxide (<10 ppm) and urinary anabasine levels (<3 ng/mL) when using low vs. high nicotine salt concentration e-liquids. | 1 month | 
| Volume of e-liquid used (in terms of superiority) | Volume of e-liquid used when using low vs. high nicotine salt concentration e-liquids. | 1 month | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 7-day point prevalence tobacco cigarette abstinence | Same as primary outcome using a less strict definition of tobacco cigarette abstinence, i.e. self-report of smoking no more than 5 cigarettes | 1 month | 
| Continuous tobacco cigarette abstinence | Self-reported continuous abstinence at 1 month (confirmed by exhaled carbon monoxide and urinary anabasine) using the stricter, i.e. not a puff and the less strict, i.e. no more than 5 cigarettes definition | 1 month | 
| 7-day point prevalence tobacco cigarette abstinence | Self-reported 7-day point prevalence abstinence at 3 and 6 months (confirmed by exhaled carbon monoxide and urinary anabasine) using the stricter, i.e. not a puff and the less strict, i.e. no more than 5 cigarettes definition | 3 and 6 months | 
| Continuous tobacco cigarette abstinence | Self-reported continuous abstinence at 3 and 6 months (confirmed by exhaled carbon monoxide and urinary anabasine) using the stricter, i.e. not a puff and the less strict, i.e. no more than 5 cigarettes definition, and when allowing a 2-week grace period from the target quit date | 3 and 6 months | 
| Number of drop-outs |  | Through study completion | 
| Time of dropping out |  | Through study completion | 
| Urinary volatile organic compounds (VOC) | Change of non-nicotine toxicants (VOC) from baseline to 1 month and 3 months of nicotine salt use | 1 and 3 months | 
| Tobacco-specific nitrosamines (TSNA) | Change of non-nicotine toxicants (TSNA) from baseline to 1 month and 3 months of nicotine salt use | 1 and 3 months | 
| Liking/rating of trial product (active arms) | Questions regarding helpfulness in refraining from smoking, how satisfying and how good the e-cigarette tastes compared to the tobacco cigarettes, if they would recommend the assigned trial product to another smoker, and any potential practical problems they might have with the handling. | 1 and 3 months | 
| Respiratory symptoms | Checklist with specific questions regarding shortness of breath, wheezing, cough or phlegm | Up to 6 months | 
| Adverse events | Checklist with specific questions regarding presence or absence of nausea, sleep disturbance, throat/mouth irritation or other | Up to 6 months | 
| Total nicotine amount vaped |  | 1 and 3 months | 
| Total volume of e-liquid consumed |  | 1 and 3 months | 
| Steroid profiles | Steroid profiles in saliva, blood and urine | Baseline, 1, 3 and 6 months | 
| Number of cigarettes smoked per day among those who fail to quit |  | Through study completion |