Clinical trial NCT03612544: The ESTxENDS Trial- Substudy on the Effect on Toxins From Using Electronic Nicotine Delivery Systems (ENDS/Vaporizer/E-cig)
Official title: Substudy of Efficacy, Safety and Toxicology of Electronic Nicotine Delivery Systems as an Aid for Smoking Cessation (ESTxENDS Trial)- the Toxins Substudy of ESTxENDS
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Smoking Cessation
Toxicity
Lead sponsor: University of Bern
Sponsor class: OTHER
Collaborators: name: University of Lausanne
name: University of Geneva, Switzerland
name: University of Zurich
name: State Hospital, St. Gallen
name: Swiss National Science Foundation
name: Krebsforschung Schweiz, Bern, Switzerland
name: Federal Office of Public Health, Switzerland
First posted: 2018-08-02
Enrollment: 1246
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: --\> 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.


Eligibility criteria: 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

Primary outcomes:
measure: Concentrations of urinary NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol)_1
timeFrame: 6 months post quit date
measure: Concentrations of urinary NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol)_2
timeFrame: 12 months post quit date
measure: Concentrations of urinary NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol)_3
timeFrame: 24 months post quit date
measure: Concentrations of urinary NNN (N-nitrosonornicotine)_1
timeFrame: 6 months post quit date
measure: Concentrations of urinary NNN (N-nitrosonornicotine)_2
timeFrame: 12 months post quit date
measure: Concentrations of urinary NNN (N-nitrosonornicotine)_3
timeFrame: 24 months post quit date
measure: Concentrations of urinary NNK (nicotine-derived nitrosamine ketone)_1
timeFrame: 6 months post quit date
measure: Concentrations of urinary NNK (nicotine-derived nitrosamine ketone)_2
timeFrame: 12 months post quit date
measure: Concentrations of urinary NNK (nicotine-derived nitrosamine ketone)_3
timeFrame: 24 months post quit date
measure: Concentrations of urinary metabolites of VOCs (volatile organic compounds)_1
timeFrame: 6 months post quit date
measure: Concentrations of urinary metabolites of VOCs (volatile organic compounds)_2
timeFrame: 12 months post quit date
measure: Concentrations of urinary metabolites of VOCs (volatile organic compounds)_3
timeFrame: 24 months post quit date
measure: Concentrations of urinary PAHs (Polycyclic aromatic hydrocarbons)_1
timeFrame: 6 months post quit date
measure: Concentrations of urinary PAHs (Polycyclic aromatic hydrocarbons)_2
timeFrame: 12 months post quit date
measure: Concentrations of urinary PAHs (Polycyclic aromatic hydrocarbons)_3
timeFrame: 24 months post quit date
measure: Concentrations of urinary heavy metals_1
timeFrame: 6 months post quit date
measure: Concentrations of urinary heavy metals_2
timeFrame: 12 months post quit date
measure: Concentrations of urinary heavy metals_3
timeFrame: 24 months post quit date
measure: Concentrations of urinary nicotine metabolites_1
timeFrame: 6 months post quit date
measure: Concentrations of urinary nicotine metabolites_2
timeFrame: 12 months post quit date
measure: Concentrations of urinary nicotine metabolites_3
timeFrame: 24 months post quit date
Secondary outcomes:
measure: Change in concentrations of urinary NNAL (4-(Methylnitrosamino)-1-(3-pyridyl)-1-butanol)
timeFrame: Change from baseline to 6,12, 24 months post quit date
measure: Change in concentrations of urinary NNN (N-nitrosonornicotine)
timeFrame: Change from baseline to 6,12, 24 months post quit date
measure: Change in concentrations of urinary NNK (nicotine-derived nitrosamine ketone)
timeFrame: Change from baseline to 6,12, 24 months post quit date
measure: Change in concentrations of urinary VOCs (volatile organic compounds)
timeFrame: Change from baseline to 6,12, 24 months post quit date
measure: Change in concentrations of urinary PAHs (Polycyclic aromatic hydrocarbons)
timeFrame: Change from baseline to 6,12, 24 months post quit date
measure: Change in concentrations of urinary heavy metals
timeFrame: Change from baseline to 6,12, 24 months post quit date
measure: Change in concentrations of urinary nicotine metabolites
timeFrame: Change from baseline to 6,12, 24 months post quit date
Other outcomes:
Locations:
city: Lausanne
country: Switzerland
facility: Unisanté, Centre universitaire de médecine générale et santé publique, Université de Lausanne
state: Vaud
city: Bern
country: Switzerland
facility: University Clinic for General Internal Medicine, Bern University Hospital
city: Geneva
country: Switzerland
facility: Département de médecine interne, Hôpitaux universitaires de Genève
city: Saint Gallen
country: Switzerland
facility: Lungenzentrum, Klinik für Pneumologie und Schlafmedizin, Kantonsspital St. Gallen
city: Zürich
country: Switzerland
facility: Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich
Study officials:
affiliation: Berner Institut für Hausarztmedizin; Universität Bern
name: Reto Auer, Prof.Dr.med
role: STUDY_DIRECTOR
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