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

NCT03612375 | Completed DMC

• 1 other identifier: 2017-02332c
• Study Type: interventional
• Target: 1,246
• Locations: 1 country
• Sites: 5

Brief 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.

Conditions

Smoking Cessation; Oxidative Stress

Outcome Measures

Primary Outcomes (6)

• 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 Outcomes (2)

• Change in urinary 8-OHdG concentrations to asses oxidative stress

  Change from baseline to 6,12, 24 months post quit date

• Change in urinary 8-isoprostane concentrations to asses oxidative stress

  Change from baseline to 6,12, 24 months post quit date

Study Arms (2)

Intervention group

EXPERIMENTAL

Other: ENDS (vaporizer/e-cig) and smoking cessation counseling

Control group

ACTIVE COMPARATOR

Other: smoking cessation counseling

Interventions

ENDS (vaporizer/e-cig) and smoking cessation counseling OTHER

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.

Intervention group

smoking cessation counseling OTHER

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.

Control group

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University of Bern: lead
• University of Lausanne: collaborator
• University of Geneva, Switzerland: collaborator
• University of Zurich: collaborator
• State Hospital, St. Gallen: collaborator
• Swiss National Science Foundation: collaborator
• Krebsforschung Schweiz, Bern, Switzerland: collaborator
• Federal Office of Public Health, Switzerland: collaborator

Study Sites (5)

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

Lausanne, Canton of Vaud, 1011, Switzerland

Location

University Clinic for General Internal Medicine, Bern University Hospital

Bern, 3010, Switzerland

Location

Département de médecine interne, Hôpitaux universitaires de Genève

Geneva, 1211, Switzerland

Location

Lungenzentrum, Klinik für Pneumologie und Schlafmedizin, Kantonsspital St. Gallen

Sankt Gallen, Switzerland

Location

Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich

Zurich, Switzerland

Location

Related Publications (12)

• 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.

  PMID: 15282395 BACKGROUND

• 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.

  PMID: 8512242 BACKGROUND

• 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.

  PMID: 17332694 BACKGROUND

• 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.

  PMID: 27622384 BACKGROUND

• 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.

  PMID: 21391783 BACKGROUND

• 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.

  PMID: 24854418 BACKGROUND

• 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.

  PMID: 19676143 BACKGROUND

• 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.

  PMID: 18522490 BACKGROUND

• 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.

  PMID: 8534261 BACKGROUND

• 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.

  PMID: 21420490 BACKGROUND

• 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.

  PMID: 14687888 BACKGROUND

• 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.

  PMID: 23530763 BACKGROUND

MeSH Terms

Conditions

Smoking Cessation

Condition Hierarchy (Ancestors)

Health Behavior; Behavior

Study Officials

• Reto Auer, Prof.Dr.med

  Berner Institut für Hausarztmedizin; Universität Bern

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Masking Details: Statisticians and laboratory personnel will be blinded to group allocation
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 2, 2018
• First Posted: August 2, 2018
• Study Start: July 16, 2018
• Primary Completion: August 31, 2023
• Study Completion: August 31, 2023
• Last Updated: November 15, 2023

Record last verified: 2023-11

Locations

CH (5)