The ESTxENDS Trial- Substudy on the Effect on Toxins From Using Electronic Nicotine Delivery Systems (ENDS/Vaporizer/E-cig)

Study Overview
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Brief Summary
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--> This is a substudy of the main ESTxENDS trial (NCT03589989). Toxins outcomes should be considered secondary outcomes of the main smoking cessation outcome formulated in NCT03589989. Cigarette smoking is the leading cause of preventable death in Switzerland. Recently, electronic nicotine delivery systems (ENDS; also called vaporizer or electronic cigarette) have become popular with smokers who want to stop smoking or reduce their exposure to inhaled chemicals since ENDS use appears to be safer than tobacco smoking. Conventional cigarettes release toxic chemicals in tobacco smoke through thermochemical degradation and pyrolysis processes by combusting tobacco, but in ENDS toxicants can be released by heating up nicotine-containing e-liquids to produce vapor. The e-liquid in ENDS is mostly made of propylene glycol (PG) and vegetal glycerin (VG) in addition to nicotine, flavorings and sometimes alcohol as a conservation agent. The heating process of the e-liquid in ENDS, has been shown to release carcinogens such as some carbonyl and volatile organic compounds (i.e., formaldehyde, acetaldehyde and acrolein). Some devices might also release heavy metals such as cadmium, lead and mercury. The source of such metals may be the metal of the device or the e-liquids. Although unexpected from the composition of the e-liquids, some studies have also detected tobacco-specific nitrosamines (TNSAs) (N'-nitrosonornicotine (NNN) and 4-(methylnitrosoamino)-1-(3-pyridyl)-1-butanone (NNK)) and polycyclic aromatic hydrocarbons (PAHs) (1- and 2-Naphtol and 1-hydroxypyrene (1-OHP)). This study will therefore test the efficacy of ENDS for cigarette smoking cessation, the safety of ENDS on adverse events and the effect of ENDS on health-related outcomes and exposure to inhaled chemicals. For the main ESTxENDS trial (NCT03589989), cigarette smokers motivated to quit smoking cigarettes will be included. Participants in the intervention group will receive an ENDS and nicotine-containing e-liquids, which they will be allowed to use ad libitum. Additionally, they will receive smoking cessation counseling. Participants in the control group will receive smoking cessation counseling only. All participants will be followed over a 24-month period. Chemicals such as VOCs, PAHs, TSNAs, heavy metals, nicotine and nicotine degradation products will first be quantified in the aerosol produced by ENDS in laboratory conditions. These chemicals and their metabolites will then be measured at baseline and at 6-, 12- and 24- months' follow-up in urine samples from study participants.

Official Title
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Substudy of Efficacy, Safety and Toxicology of Electronic Nicotine Delivery Systems as an Aid for Smoking Cessation (ESTxENDS Trial)- the Toxins Substudy of ESTxENDS

Conditions
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Smoking Cessation, Toxicity

Intervention / Treatment
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* Other: ENDS (Vaporizer/e-cig) and smoking cessation counseling
* Other: Smoking cessation counseling


Participation Criteria
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Eligibility Criteria
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Inclusion criteria: Informed Consent as documented by signature Persons aged 18 or older Currently smoking 5 or more cigarettes a day for at least 12 months Willing to try to quit smoking within the next 3 months, Persons providing a valid phone number, a valid email address and/or a valid postal address. Exclusion criteria: Known hypersensitivity or allergy to contents of the e-liquid Participation in another study with investigational drug within the 30 days preceding the baseline visit and during the present study where interactions are to be expected Women who are pregnant or breast feeding Intention to become pregnant during the course of the scheduled study intervention, i.e. within the first 6-months of the study Persons having used ENDS or tobacco heating systems regularly in the 3 months preceding the baseline visit Persons having used nicotine replacement therapy (NRT) or other medications with demonstrated efficacy as an aid for smoking cessation such as varenicline or bupropion within the 3 months preceding the baseline visit Persons who cannot attend the 6- month follow-up visit for any reason Cannot understand instructions delivered in person or by phone, or otherwise unable to participate in study procedures

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: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br> | Other: ENDS (Vaporizer/e-cig) and smoking cessation counseling<br>* Participants in the intervention group will receive an ENDS and nicotine-containing e-liquids, which they will be allowed to use ad libitum. Additionally, they will receive smoking cessation counseling. Participants will be allowed to additionally use nicotine replacement therapy. All participants will be followed over a 24-month period. Smoking cessation counseling will be provided in person at the first clinical visit and then over the phone at the target quit date one week later and again at week 2, 4 and 8 after the target quit date. After 6, 12 and 24 months, participants will be asked to come to a clinical visit.<br>|
| Active Comparator: Control group<br> | Other: Smoking cessation counseling<br>* Participants in the control group will receive smoking cessation counseling only. Participants will be allowed to additionally use nicotine replacement therapy. All participants will be followed over a 24-month period. Smoking cessation counseling will be provided in person at the first clinical visit and then over the phone at the target quit date one week later and again at week 2, 4 and 8 after the target quit date. After 6, 12 and 24 months, participants will be asked to come to a clinical visit.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of urinary NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol)_1 | Measurement of NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol) in urine | 6 months post quit date | 
| Concentrations of urinary NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol)_2 | Measurement of NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol) in urine | 12 months post quit date | 
| Concentrations of urinary NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol)_3 | Measurement of NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol) in urine | 24 months post quit date | 
| Concentrations of urinary NNN (N-nitrosonornicotine)_1 | Measurement of NNN (N-nitrosonornicotine) in urine | 6 months post quit date | 
| Concentrations of urinary NNN (N-nitrosonornicotine)_2 | Measurement of NNN (N-nitrosonornicotine) in urine | 12 months post quit date | 
| Concentrations of urinary NNN (N-nitrosonornicotine)_3 | Measurement of NNN (N-nitrosonornicotine) in urine | 24 months post quit date | 
| Concentrations of urinary NNK (nicotine-derived nitrosamine ketone)_1 | Measurement of NNK (nicotine-derived nitrosamine ketone) in urine | 6 months post quit date | 
| Concentrations of urinary NNK (nicotine-derived nitrosamine ketone)_2 | Measurement of NNK (nicotine-derived nitrosamine ketone) in urine | 12 months post quit date | 
| Concentrations of urinary NNK (nicotine-derived nitrosamine ketone)_3 | Measurement of NNK (nicotine-derived nitrosamine ketone) in urine | 24 months post quit date | 
| Concentrations of urinary metabolites of VOCs (volatile organic compounds)_1 | Measurements of metabolites of VOCs in urine | 6 months post quit date | 
| Concentrations of urinary metabolites of VOCs (volatile organic compounds)_2 | Measurements of metabolites of VOCs in urine | 12 months post quit date | 
| Concentrations of urinary metabolites of VOCs (volatile organic compounds)_3 | Measurements of metabolites of VOCs in urine | 24 months post quit date | 
| Concentrations of urinary PAHs (Polycyclic aromatic hydrocarbons)_1 | Measurement of PAHs (Polycyclic aromatic hydrocarbons) in urine | 6 months post quit date | 
| Concentrations of urinary PAHs (Polycyclic aromatic hydrocarbons)_2 | Measurement of PAHs (Polycyclic aromatic hydrocarbons) in urine | 12 months post quit date | 
| Concentrations of urinary PAHs (Polycyclic aromatic hydrocarbons)_3 | Measurement of PAHs (Polycyclic aromatic hydrocarbons) in urine | 24 months post quit date | 
| Concentrations of urinary heavy metals_1 | Measurement of heavy metals in urine | 6 months post quit date | 
| Concentrations of urinary heavy metals_2 | Measurement of heavy metals in urine | 12 months post quit date | 
| Concentrations of urinary heavy metals_3 | Measurement of heavy metals in urine | 24 months post quit date | 
| Concentrations of urinary nicotine metabolites_1 | Measurement of nicotine metabolites in urine | 6 months post quit date | 
| Concentrations of urinary nicotine metabolites_2 | Measurement of nicotine metabolites in urine | 12 months post quit date | 
| Concentrations of urinary nicotine metabolites_3 | Measurement of nicotine metabolites in urine | 24 months post quit date | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in concentrations of urinary NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol) | Change of NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol) concentrations in urine from baseline to 6, 12, and 24 months post quit date. | Change from baseline to 6,12, 24 months post quit date | 
| Change in concentrations of urinary NNN (N-nitrosonornicotine) | Change of NNN (N-nitrosonornicotine) concentrations in urine from baseline to 6, 12, and 24 months post quit date. | Change from baseline to 6,12, 24 months post quit date | 
| Change in concentrations of urinary NNK (nicotine-derived nitrosamine ketone) | Change of NNK (nicotine-derived nitrosamine ketone) concentrations in urine from baseline to 6, 12, and 24 months post quit date. | Change from baseline to 6,12, 24 months post quit date | 
| Change in concentrations of urinary VOCs (volatile organic compounds) | Change of VOCs (volatile organic compounds) concentrations in urine from baseline to 6, 12, and 24 months post quit date. | Change from baseline to 6,12, 24 months post quit date | 
| Change in concentrations of urinary PAHs (Polycyclic aromatic hydrocarbons) | Change of PAHs (Polycyclic aromatic hydrocarbons) concentrations in urine from baseline to 6, 12, and 24 months post quit date. | Change from baseline to 6,12, 24 months post quit date | 
| Change in concentrations of urinary heavy metals | Change of heavy metals concentrations in urine from baseline to 6, 12, and 24 months post quit date. | Change from baseline to 6,12, 24 months post quit date | 
| Change in concentrations of urinary nicotine metabolites | Change of nicotine metabolites concentrations in urine from baseline to 6, 12, and 24 months post quit date. | Change from baseline to 6,12, 24 months post quit date |