The ESTxENDS Trial- Substudy on the Effects of Using Electronic Nicotine Delivery Systems (ENDS/Vaporizer/E-cig) on Respiratory Symptoms (ESTxENDS)

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

--> This is a substudy of the main ESTxENDS trial (NCT03589989). Respiratory symptoms 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. Cigarette smoking eventually kills one in two smokers, mostly through cancer, heart disease and respiratory failure. 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.

Studies suggest that ENDS use improves health outcomes, such as reducing respiratory symptoms, and presents only minimal respiratory risks, such as mild throat irritation and dry cough.

In a prospective 6-month randomized, controlled trial evaluating smoking reduction/abstinence in 300 smokers not intending to quit experimenting two different nicotine strengths of a e-cigarette model compared to its non-nicotine choice, respiratory symptoms similarly improved in all three study groups. One study compared the short-term effects of cigarette smoking to ENDS use and found that cigarette smoking led to an acute reduction in lung function, which was not observed with ENDS. Findings on short-term airway resistance is conflicting. Short term increase in resistance in ENDS users might be caused by aerosolizing the liquid, and not by the same substances that harm lung function in cigarette smokers. Smokers who shifted from tobacco cigarettes to ENDS have offered anecdotes of dramatically improved lung function, but animal models suggest that ENDS liquids can increase markers of asthma. No large randomized trials have tested the effect of ENDS on respiratory symptoms.

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-months period. Respiratory symptoms such as chronic obstructive pulmonary disease (COPD), asthma and dyspnea will be assessed by means of questionnaires at baseline and at 6-, 12- and 24-months follow up. This trial will provide useful data on changes in respiratory symptoms in a large sample of participants.

Study Overview

• Status: Completed
• Conditions: Smoking Cessation; Respiratory Disease
• 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: 16 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 respiratory symptoms (Chronic obstructive pulmonary disease (COPD)_1	Measured using COPD assessment test (CAT). The COPD Assessment Test (CAT) is a questionnaire for people with COPD. It is designed to measure the impact of COPD on a person's life, and how this changes over time. The CAT has 8 items and the scaling of each item is from 1 to 5. Range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD on a patient's life.	6 months post quit date
Assessment of respiratory symptoms (Chronic obstructive pulmonary disease (COPD)_2	Measured using COPD assessment test (CAT). The COPD Assessment Test (CAT) is a questionnaire for people with COPD. It is designed to measure the impact of COPD on a person's life, and how this changes over time. The CAT has 8 items and the scaling of each item is from 1 to 5. Range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD on a patient's life.	12 months post quit date
Assessment of respiratory symptoms (Chronic obstructive pulmonary disease (COPD)_3	Measured using COPD assessment test (CAT). The COPD Assessment Test (CAT) is a questionnaire for people with COPD. It is designed to measure the impact of COPD on a person's life, and how this changes over time. The CAT has 8 items and the scaling of each item is from 1 to 5. Range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD on a patient's life.	24 months post quit date
Assessment of respiratory symptoms (Dyspnea)_1	Measured using mMRC- Dyspnea scale. The mMRC Dyspnea Scale quantifies disability attributable to breathlessness, and is useful for characterizing baseline dyspnea in patients with respiratory diseases. The severity of dyspnea is rated on a scale of 0 to 4.	6 months post quit date
Assessment of respiratory symptoms (Dyspnea)_2	Measured using mMRC- Dyspnea scale. The mMRC Dyspnea Scale quantifies disability attributable to breathlessness, and is useful for characterizing baseline dyspnea in patients with respiratory diseases. The severity of dyspnea is rated on a scale of 0 to 4.	12 months post quit date
Assessment of respiratory symptoms (Dyspnea)_3	Measured using mMRC- Dyspnea scale. The mMRC Dyspnea Scale quantifies disability attributable to breathlessness, and is useful for characterizing baseline dyspnea in patients with respiratory diseases. The severity of dyspnea is rated on a scale of 0 to 4.	24 months post quit date
Assessment of respiratory symptoms (Asthma)_1	Measured using the Asthma Control Test ACT and questions from the European community respiratory health survey ECRHS. The ACT is self-administered tool with 5-items assessing the frequency of shortness of breath and general asthma symptoms, use of rescue medications, the effect of asthma on daily functioning, and overall self-assessment of asthma control. The scaling of items is on a 5-point scale. The scores range from 5 to 25, with higher scores reflecting greater asthma control.	6 months post quit date
Assessment of respiratory symptoms (Asthma)_2	Measured using the Asthma Control Test ACT and questions from the European community respiratory health survey ECRHS. The ACT is self-administered tool with 5-items assessing the frequency of shortness of breath and general asthma symptoms, use of rescue medications, the effect of asthma on daily functioning, and overall self-assessment of asthma control. The scaling of items is on a 5-point scale. The scores range from 5 to 25, with higher scores reflecting greater asthma control.	12 months post quit date
Assessment of respiratory symptoms (Asthma)_3	Measured using the Asthma Control Test ACT and questions from the European community respiratory health survey ECRHS. The ACT is self-administered tool with 5-items assessing the frequency of shortness of breath and general asthma symptoms, use of rescue medications, the effect of asthma on daily functioning, and overall self-assessment of asthma control. The scaling of items is on a 5-point scale. The scores range from 5 to 25, with higher scores reflecting greater asthma control.	24 months post quit date

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in respiratory symptoms (Chronic obstructive pulmonary disease (COPD)	Measured using COPD assessment test (CAT). The COPD Assessment Test (CAT) is a questionnaire for people with COPD. It is designed to measure the impact of COPD on a person's life, and how this changes over time. The CAT has 8 items and the scaling of each item is from 1 to 5. Range of CAT scores from 0-40. Higher scores denote a more severe impact of COPD on a patient's life.	Change from baseline to 6,12, 24 months post quit date
Change in respiratory symptoms (Dyspnea)	Measured using mMRC- Dyspnea scale. The mMRC Dyspnea Scale quantifies disability attributable to breathlessness, and is useful for characterizing baseline dyspnea in patients with respiratory diseases. The severity of dyspnea is rated on a scale of 0 to 4.	Change from baseline to 6,12, 24 months post quit date
Change in respiratory symptoms (Asthma)	Measured using the Asthma Control Test ACT and questions from the European community respiratory health survey ECRHS. The ACT is self-administered tool with 5-items assessing the frequency of shortness of breath and general asthma symptoms, use of rescue medications, the effect of asthma on daily functioning, and overall self-assessment of asthma control. The scaling of items is on a 5-point scale. The scores range from 5 to 25, with higher scores reflecting greater asthma control.	Change from baseline to 6,12, 24 months post quit date
Assessment of adverse respiratory effects due to ENDS use	Adverse respiratory effects due to ENDS use are assessed using questionnaires or over the phone.	1 week post quit date
Assessment of adverse respiratory effects due to ENDS use	Adverse respiratory effects due to ENDS use are assessed using questionnaires or over the phone.	2 weeks post quit date
Assessment of adverse respiratory effects due to ENDS use	Adverse respiratory effects due to ENDS use are assessed using questionnaires or over the phone.	4 weeks post quit date
Assessment of adverse respiratory effects due to ENDS use	Adverse respiratory effects due to ENDS use are assessed using questionnaires or over the phone.	8 weeks post quit date
Assessment of adverse respiratory effects due to ENDS use	Adverse respiratory effects due to ENDS use are assessed using questionnaires or over the phone.	6,12, 24 months post quit date
Assessment of adverse respiratory effects due tobacco cigarette use	Adverse respiratory effects due to tobacco cigarette use use are assessed using questionnaires or over the phone.	Baseline
Assessment of adverse respiratory effects due tobacco cigarette use	Adverse respiratory effects due to tobacco cigarette use use are assessed using questionnaires or over the phone.	1 week post quit date
Assessment of adverse respiratory effects due tobacco cigarette use	Adverse respiratory effects due to tobacco cigarette use use are assessed using questionnaires or over the phone.	2 weeks post quit date
Assessment of adverse respiratory effects due tobacco cigarette use	Adverse respiratory effects due to tobacco cigarette use use are assessed using questionnaires or over the phone.	4 weeks post quit date
Assessment of adverse respiratory effects due tobacco cigarette use	Adverse respiratory effects due to tobacco cigarette use use are assessed using questionnaires or over the phone.	8 weeks post quit date
Assessment of adverse respiratory effects due tobacco cigarette use	Adverse respiratory effects due to tobacco cigarette use use are assessed using questionnaires or over the phone.	6,12, 24 months post quit date
Assessment of adverse respiratory effects due tobacco cigarette use	Adverse respiratory effects due to tobacco cigarette use use are assessed using questionnaires or over the phone.	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; Universität Bern

Publications and helpful links

General Publications

• Caponnetto P, Campagna D, Cibella F, Morjaria JB, Caruso M, Russo C, Polosa R. EffiCiency and Safety of an eLectronic cigAreTte (ECLAT) as tobacco cigarettes substitute: a prospective 12-month randomized control design study. PLoS One. 2013 Jun 24;8(6):e66317. doi: 10.1371/journal.pone.0066317. Print 2013. Erratum In: PLoS One. 2014;9(1). doi:10.1371/annotation/e12c22d3-a42b-455d-9100-6c7ee45d58d0.
• Farsalinos KE, Polosa R. Safety evaluation and risk assessment of electronic cigarettes as tobacco cigarette substitutes: a systematic review. Ther Adv Drug Saf. 2014 Apr;5(2):67-86. doi: 10.1177/2042098614524430.
• Flouris AD, Chorti MS, Poulianiti KP, Jamurtas AZ, Kostikas K, Tzatzarakis MN, Wallace Hayes A, Tsatsakis AM, Koutedakis Y. Acute impact of active and passive electronic cigarette smoking on serum cotinine and lung function. Inhal Toxicol. 2013 Feb;25(2):91-101. doi: 10.3109/08958378.2012.758197.
• Lim HB, Kim SH. Inhallation of e-Cigarette Cartridge Solution Aggravates Allergen-induced Airway Inflammation and Hyper-responsiveness in Mice. Toxicol Res. 2014 Mar;30(1):13-8. doi: 10.5487/TR.2014.30.1.013.
• Vardavas CI, Anagnostopoulos N, Kougias M, Evangelopoulou V, Connolly GN, Behrakis PK. Short-term pulmonary effects of using an electronic cigarette: impact on respiratory flow resistance, impedance, and exhaled nitric oxide. Chest. 2012 Jun;141(6):1400-1406. doi: 10.1378/chest.11-2443. Epub 2011 Dec 22.
• Jha P, Ramasundarahettige C, Landsman V, Rostron B, Thun M, Anderson RN, McAfee T, Peto R. 21st-century hazards of smoking and benefits of cessation in the United States. N Engl J Med. 2013 Jan 24;368(4):341-50. doi: 10.1056/NEJMsa1211128.

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: June 25, 2018
• First Submitted That Met QC Criteria: August 14, 2018
• First Posted (Actual): August 15, 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: Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory
• Other Study ID Numbers: 2017-02332a

Drug and device information, study documents

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