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

Smoking Cessation Clinical Trial

— ESTxENDS  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03612375
• Other study ID #: 2017-02332c
• Status: Completed
• Phase: N/A
• Start date: July 16, 2018
• Est. completion date: August 31, 2023

Study information

• Verified date: November 2023
• Source: University of Bern
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

--> 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 1246
• Est. completion date: August 31, 2023
• Est. primary completion date: August 31, 2023
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Oxidative Stress
• Smoking Cessation

Intervention

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 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.
• 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 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.

Locations

Country	Name	City	State
Switzerland	University Clinic for General Internal Medicine, Bern University Hospital	Bern
Switzerland	Département de médecine interne, Hôpitaux universitaires de Genève	Geneva
Switzerland	Unisanté, Centre universitaire de médecine générale et santé publique, Université de Lausanne	Lausanne	Vaud
Switzerland	Lungenzentrum, Klinik für Pneumologie und Schlafmedizin, Kantonsspital St. Gallen	Saint Gallen
Switzerland	Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich	Zürich

Sponsors (8)

Lead Sponsor	Collaborator
University of Bern	Federal Office of Public Health, Switzerland, Krebsforschung Schweiz, Bern, Switzerland, State Hospital, St. Gallen, Swiss National Science Foundation, University of Geneva, Switzerland, University of Lausanne, University of Zurich

Country where clinical trial is conducted

Switzerland, 

References & Publications (12)

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. — View Citation

Campos C, Guzman R, Lopez-Fernandez E, Casado A. Urinary biomarkers of oxidative/nitrosative stress in healthy smokers. Inhal Toxicol. 2011 Feb;23(3):148-56. doi: 10.3109/08958378.2011.554460. — View Citation

Hartmann-Boyce J, McRobbie H, Bullen C, Begh R, Stead LF, Hajek P. Electronic cigarettes for smoking cessation. Cochrane Database Syst Rev. 2016 Sep 14;9(9):CD010216. doi: 10.1002/14651858.CD010216.pub3. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

Morrow JD, Roberts LJ 2nd. The isoprostanes. Current knowledge and directions for future research. Biochem Pharmacol. 1996 Jan 12;51(1):1-9. doi: 10.1016/0006-2952(95)02072-1. — View Citation

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. doi: 10.1111/j.1749-6632.1993.tb39148.x. No abstract available. — View Citation

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. — View Citation

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. doi: 10.1136/thx.2003.012468. — View Citation

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. doi: 10.1016/j.cccn.2003.09.010. — View Citation

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. doi: 10.1254/jphs.fp0061055. Epub 2007 Mar 2. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Urinary 8-OHdG concentrations to asses oxidative stress_1	Oxidative stress assessed by 8-OHdG concentrations in urine.	6 months post quit date
Primary	Urinary 8-OHdG concentrations to asses oxidative stress_2	Oxidative stress assessed by 8-OHdG concentrations in urine.	12 months post quit date
Primary	Urinary 8-OHdG concentrations to asses oxidative stress_3	Oxidative stress assessed by 8-OHdG concentrations in urine.	24 months post quit date
Primary	Urinary 8-isoprostane concentrations to asses oxidative stress_1	Oxidative stress assessed by 8-isoprostane concentrations in urine.	6 months post quit date
Primary	Urinary 8-isoprostane concentrations to asses oxidative stress_2	Oxidative stress assessed by 8-isoprostane concentrations in urine.	12 months post quit date
Primary	Urinary 8-isoprostane concentrations to asses oxidative stress_3	Oxidative stress assessed by 8-isoprostane concentrations in urine.	24 months post quit date
Secondary	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
Secondary	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