ESTxENDS Trial- Oxidative Stress Induced by Electronic Nicotine Delivery Systems (ENDS/Vaporizer/E-cig) Measured in EBC (ESTxENDS)

• ClinicalTrials.gov Identifier: NCT03612453
• Recruitment Status: Completed
• First Posted: August 2, 2018
• Last Update Posted: February 14, 2022
• Sponsor: University of Bern
• Collaborators: University of Lausanne; University of Geneva, Switzerland; Swiss National Science Foundation
• Information provided by (Responsible Party): University of Bern

Study Description

Brief Summary:

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 exhaled breath condensates: 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 exhaled breath condensates (EBC).

For this trial, 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 6-month period. Measures of oxidative stress by means of exhaled breath condensates and urine samples will be assessed at baseline and at 6- months' follow-up by asking to breathe for 20 minutes in a vial kept frozen at -10°C to collect around 2 mL of EBC.

Condition or disease	Intervention/treatment	Phase
Smoking Cessation; Oxidative Stress	Other: ENDS (vaporizer/e-cig) and smoking cessation counseling; Other: Smoking cessation counseling	Not Applicable

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 155 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Masking Description: Statisticians and laboratory personnel will be blinded to group allocation
• Primary Purpose: Prevention
• Official Title: Efficacy, Safety and Toxicology of Electronic Nicotine Delivery Systems as an Aid for Smoking Cessation (ESTxENDS Trial)
• Actual Study Start Date: April 3, 2019
• Actual Primary Completion Date: February 1, 2022
• Actual Study Completion Date: February 1, 2022

Arms and Interventions

Arm	Intervention/treatment
Experimental: Intervention group	Other: ENDS (vaporizer/e-cig) and smoking cessation counseling; 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 6-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 months, participants will be asked to come to a final clinical visit.
Active Comparator: Control group	Other: Smoking cessation counseling; 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 6-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 months, participants will be asked to come to a final clinical visit.

Outcome Measures

Primary Outcome Measures :

1. Oxidative stress assessment (8-OHdG) [ Time Frame: 6 months post quit date ]
   Oxidative stress assessed by 8-OHdG in exhaled breath condensate (EBC)
2. Oxidative stress assessment (8-isoprostane) [ Time Frame: 6 months post quit date ]
   Oxidative stress assessed by 8-isoprostane concentrations in exhaled breath condensate (EBC)

Secondary Outcome Measures :

1. Change in oxidative stress (8-OHdG) [ Time Frame: Change from baseline to 6 months post quit date ]
   Change in oxidative stress assessed by measuring 8-OHdG in exhaled breath condensate (EBC)
2. Change in oxidative stress (8-isoprostane) [ Time Frame: Change from baseline to 6 months post quit date ]
   Change in oxidative stress assessed by measuring 8-isoprostane in exhaled breath condensate (EBC)

Eligibility Criteria

• Ages Eligible for Study: 18 Years and older (Adult, Older Adult)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

Switzerland

Unisanté, Centre universitaire de médecine générale et santé publique, Université de Lausanne

Lausanne, Vaud, Switzerland, 1011

Sponsors and Collaborators

University of Bern

University of Lausanne

University of Geneva, Switzerland

Swiss National Science Foundation

Investigators

• Study Director: Reto Auer, Prof.Dr.med; Berner Institut für Hausarztmedizin; Universität Bern

More Information

Publications:

van der Vaart H, Postma DS, Timens W, ten Hacken NH. Acute effects of cigarette smoke on inflammation and oxidative stress: a review. Thorax. 2004 Aug;59(8):713-21. Review.

Pryor WA, Stone K. Oxidants in cigarette smoke. Radicals, hydrogen peroxide, peroxynitrate, and peroxynitrite. Ann N Y Acad Sci. 1993 May 28;686:12-27; discussion 27-8. Review.

Yamaguchi Y, Nasu F, Harada A, Kunitomo M. Oxidants in the gas phase of cigarette smoke pass through the lung alveolar wall and raise systemic oxidative stress. J Pharmacol Sci. 2007 Mar;103(3):275-82. Epub 2007 Mar 2.

Haswell LE, Papadopoulou E, Newland N, Shepperd CJ, Lowe FJ. A cross-sectional analysis of candidate biomarkers of biological effect in smokers, never-smokers and ex-smokers. Biomarkers. 2014 Aug;19(5):356-67. doi: 10.3109/1354750X.2014.912354. Epub 2014 May 22.

Lowe FJ, Gregg EO, McEwan M. Evaluation of biomarkers of exposure and potential harm in smokers, former smokers and never-smokers. Clin Chem Lab Med. 2009;47(3):311-20. doi: 10.1515/CCLM.2009.069.

Basu S. F2-isoprostanes in human health and diseases: from molecular mechanisms to clinical implications. Antioxid Redox Signal. 2008 Aug;10(8):1405-34. doi: 10.1089/ars.2007.1956. Review.

Morrow JD, Roberts LJ 2nd. The isoprostanes. Current knowledge and directions for future research. Biochem Pharmacol. 1996 Jan 12;51(1):1-9. Review.

Seet RC, Lee CY, Loke WM, Huang SH, Huang H, Looi WF, Chew ES, Quek AM, Lim EC, Halliwell B. Biomarkers of oxidative damage in cigarette smokers: which biomarkers might reflect acute versus chronic oxidative stress? Free Radic Biol Med. 2011 Jun 15;50(12):1787-93. doi: 10.1016/j.freeradbiomed.2011.03.019. Epub 2011 Mar 17.

Wu LL, Chiou CC, Chang PY, Wu JT. Urinary 8-OHdG: a marker of oxidative stress to DNA and a risk factor for cancer, atherosclerosis and diabetics. Clin Chim Acta. 2004 Jan;339(1-2):1-9. Review.

Lowe FJ, Luettich K, Gregg EO. Lung cancer biomarkers for the assessment of modified risk tobacco products: an oxidative stress perspective. Biomarkers. 2013 May;18(3):183-95. doi: 10.3109/1354750X.2013.777116. Epub 2013 Mar 27. Review.

• Responsible Party: University of Bern
• ClinicalTrials.gov Identifier: NCT03612453
• Other Study ID Numbers: 2017-02332d
• First Posted: August 2, 2018
• Last Update Posted: February 14, 2022
• Last Verified: February 2022

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No