ESTxENDS Trial-Substudy on Oxidative Stress Induced by Electronic Nicotine Delivery Systems (ENDS) Measured in Urine

Study Overview
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Brief Summary
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--> This is a substudy of the main ESTxENDS trial (NCT03589989). Oxidative stress 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 and still more than a quarter of the Swiss population smokes cigarettes. 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. Smoking induces inflammation leading to acute and chronic oxidative stress, both evidenced in in vitro and in vivo studies. Tobacco-smoke contains free reactive radicals that generate reactive oxygen species (ROS). Afterwards ROS in turn induce oxidative stress, which likely plays a key role in causing airways and related pathologies linked to tobacco-smoke exposure. Acute and chronic oxidative stress can be measured by quantifying two biomarkers in urine samples: 8-iso-prostaglandin F2α (8-isoprostane) and 8-Oxo-2'-deoxyguanosine (8-OHdG). 8-isoprostane, a marker of lipoperoxidation, results mainly from the non-enzymatic action of free radical attack on arachidonic fatty acids. 8-OHdG is a marker of DNA oxidation caused by ROS, and a predictor of lung cancer. Oxidative stress between smokers who quit (with or without ENDS) and those who use ENDS for a long time have not yet been assessed in the setting of a randomized controlled trial (RCT). This study will therefore test the efficacy of ENDS for cigarette smoking cessation, the safety of ENDS on adverse events, the exposure to inhaled chemicals and the effect of ENDS on health-related outcomes, in particular by measuring oxidative stress in urine samples. 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. Measures of oxidative stress by means of exhaled breath condensates and urine samples will be assessed at baseline and at 6-, 12- and 24- months' follow-up.

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 Oxidative Stress Substudy of ESTxENDS

Conditions
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Smoking Cessation, Oxidative Stress

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 study Persons having used ENDS regularly in the 3 months preceding the baseline visit Persons having used nicotine replacement therapy (NRT) or other drug therapy helping smokers quit (varenicline, bupropion) within the 3 months preceding the baseline visit Plans to move out of the country within the next 6 months, or 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 |
| --- | --- | --- |
| Urinary 8-OHdG concentrations to asses oxidative stress_1 | Oxidative stress assessed by 8-OHdG concentrations in urine. | 6 months post quit date | 
| Urinary 8-OHdG concentrations to asses oxidative stress_2 | Oxidative stress assessed by 8-OHdG concentrations in urine. | 12 months post quit date | 
| Urinary 8-OHdG concentrations to asses oxidative stress_3 | Oxidative stress assessed by 8-OHdG concentrations in urine. | 24 months post quit date | 
| Urinary 8-isoprostane concentrations to asses oxidative stress_1 | Oxidative stress assessed by 8-isoprostane concentrations in urine. | 6 months post quit date | 
| Urinary 8-isoprostane concentrations to asses oxidative stress_2 | Oxidative stress assessed by 8-isoprostane concentrations in urine. | 12 months post quit date | 
| Urinary 8-isoprostane concentrations to asses oxidative stress_3 | Oxidative stress assessed by 8-isoprostane concentrations in urine. | 24 months post quit date | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in urinary 8-OHdG concentrations to asses oxidative stress | Oxidative stress assessed by 8-OHdG concentrations in urine. | Change from baseline to 6,12, 24 months post quit date | 
| Change in urinary 8-isoprostane concentrations to asses oxidative stress | Oxidative stress assessed by 8-isoprostane concentrations in urine. | Change from baseline to 6,12, 24 months post quit date |