The ESTxENDS Trial- Substudy on the Effects of Using Electronic Nicotine Delivery Systems (ENDS) on Depression (ESTxENDS)

Efficacy, Safety and Toxicology of Electronic Nicotine Delivery Systems as an Aid for Smoking Cessation (ESTxENDS Trial)- the Depression Substudy of ESTxENDS

--> This is a substudy of the main ESTxENDS trial (NCT03589989). Depression 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. Smoking and depression are strongly associated. Individuals with depression are twice as likely to be smokers than persons without a depression. Studies have shown that attempts to quit tobacco smoking are more likely to fail for individuals with depression than without. Depressive symptoms are common in prolonged nicotine withdrawal and individuals with depression are more nicotine dependent and more likely to suffer depressive symptoms during nicotine withdrawal compared to smokers in the general population.

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. ENDS with nicotine containing e-liquids may be effective in assisting with tobacco smoking cessation without suffering depressive symptoms.

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 such as depression 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. Presence and severity of depression will be assessed using the 9-question depression scale from the patient health questionnaire (PHQ-9) at baseline and at 6, 12 and 24 months' follow-up.

Study Overview

• Status: Completed
• Conditions: Depression; Smoking Cessation
• Intervention / Treatment: Other: ENDS (vaporizer/e-cig) and smoking cessation counseling; Other: Smoking cessation counseling

• Study Type: Interventional
• Enrollment (Actual): 1246
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Switzerland
  • Bern, Switzerland, 3010
    • University Clinic for General Internal Medicine, Bern University Hospital
  • Geneva, Switzerland, 1211
    • Département de médecine interne, Hôpitaux universitaires de Genève
  • Saint Gallen, Switzerland
    • Lungenzentrum, Klinik für Pneumologie und Schlafmedizin, Kantonsspital St. Gallen
  • Zürich, Switzerland
    • Epidemiology, Biostatistics and Prevention Institute (EBPI), University of Zurich
  • Vaud
    • Lausanne, Vaud, Switzerland, 1011
      • Unisanté, Centre universitaire de médecine générale et santé publique, Université de Lausanne

Participation Criteria

Eligibility Criteria

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

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / 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 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.
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 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of severity of self-reported symptoms of depression_1	Measured using the 9-question depression scale from the patient health questionnaire (PHQ-9). The PHQ-9 is it is used to monitor the severity of depression. The PHQ-9 is the depression module, which scores each of the nine DSM-IV criteria as "0" (not at all) to "3" (nearly every day).	6 months post quit date
Assessment of severity of self-reported symptoms of depression_2	Measured using the 9-question depression scale from the patient health questionnaire (PHQ-9). The PHQ-9 is it is used to monitor the severity of depression. The PHQ-9 is the depression module, which scores each of the nine DSM-IV criteria as "0" (not at all) to "3" (nearly every day).	12 months post quit date
Assessment of severity of self-reported symptoms of depression_3	Measured using the 9-question depression scale from the patient health questionnaire (PHQ-9). The PHQ-9 is it is used to monitor the severity of depression. The PHQ-9 is the depression module, which scores each of the nine DSM-IV criteria as "0" (not at all) to "3" (nearly every day).	24 months post quit date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Assessment of change of severity of self-reported symptoms of depression	Measured using the 9-question depression scale from the patient health questionnaire (PHQ-9). The PHQ-9 is it is used to monitor the severity of depression. The PHQ-9 is the depression module, which scores each of the nine DSM-IV criteria as "0" (not at all) to "3" (nearly every day).	Change from baseline to 6,12, 24 months post quit date

Collaborators and Investigators

• Sponsor: University of Bern
• Collaborators: University of Zurich; Swiss National Science Foundation; University of Lausanne; University of Geneva, Switzerland; State Hospital, St. Gallen; Krebsforschung Schweiz, Bern, Switzerland; Federal Office of Public Health, Switzerland
• Investigators: Study Director: Reto Auer, Prof.Dr.med, Berner Institut für Hausarztmedizin (BIHAM)

Publications and helpful links

General Publications

• Lasser K, Boyd JW, Woolhandler S, Himmelstein DU, McCormick D, Bor DH. Smoking and mental illness: A population-based prevalence study. JAMA. 2000 Nov 22-29;284(20):2606-10. doi: 10.1001/jama.284.20.2606.
• Glassman AH. Cigarette smoking: implications for psychiatric illness. Am J Psychiatry. 1993 Apr;150(4):546-53. doi: 10.1176/ajp.150.4.546.
• Gierisch JM, Bastian LA, Calhoun PS, McDuffie JR, Williams JW Jr. Smoking cessation interventions for patients with depression: a systematic review and meta-analysis. J Gen Intern Med. 2012 Mar;27(3):351-60. doi: 10.1007/s11606-011-1915-2. Epub 2011 Oct 26.
• Kalman D, Morissette SB, George TP. Co-morbidity of smoking in patients with psychiatric and substance use disorders. Am J Addict. 2005 Mar-Apr;14(2):106-23. doi: 10.1080/10550490590924728.
• Hall SM, Humfleet GL, Munoz RF, Reus VI, Robbins JA, Prochaska JJ. Extended treatment of older cigarette smokers. Addiction. 2009 Jun;104(6):1043-52. doi: 10.1111/j.1360-0443.2009.02548.x. Epub 2009 Apr 9. Erratum In: Addiction. 2011 Jun;106(6):1204.
• Ziedonis D, Hitsman B, Beckham JC, Zvolensky M, Adler LE, Audrain-McGovern J, Breslau N, Brown RA, George TP, Williams J, Calhoun PS, Riley WT. Tobacco use and cessation in psychiatric disorders: National Institute of Mental Health report. Nicotine Tob Res. 2008 Dec;10(12):1691-715. doi: 10.1080/14622200802443569.
• Weinberger AH, Pilver CE, Desai RA, Mazure CM, McKee SA. The relationship of major depressive disorder and gender to changes in smoking for current and former smokers: longitudinal evaluation in the US population. Addiction. 2012 Oct;107(10):1847-56. doi: 10.1111/j.1360-0443.2012.03889.x. Epub 2012 May 17.
• Bolam B, West R, Gunnell D. Does smoking cessation cause depression and anxiety? Findings from the ATTEMPT cohort. Nicotine Tob Res. 2011 Mar;13(3):209-14. doi: 10.1093/ntr/ntq244. Epub 2011 Feb 17.
• Weinberger AH, Mazure CM, Morlett A, McKee SA. Two decades of smoking cessation treatment research on smokers with depression: 1990-2010. Nicotine Tob Res. 2013 Jun;15(6):1014-31. doi: 10.1093/ntr/nts213. Epub 2012 Oct 25.

Study record dates

Study Major Dates

• Study Start (Actual): July 16, 2018
• Primary Completion (Actual): August 31, 2023
• Study Completion (Actual): August 31, 2023

Study Registration Dates

• First Submitted: July 2, 2018
• First Submitted That Met QC Criteria: July 26, 2018
• First Posted (Actual): July 27, 2018

Study Record Updates

• Last Update Posted (Actual): November 15, 2023
• Last Update Submitted That Met QC Criteria: November 13, 2023
• Last Verified: November 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Behavioral Symptoms; Mental Disorders; Mood Disorders; Depression; Depressive Disorder
• Other Study ID Numbers: 2017-02332f

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No