The ESTxENDS Trial: Pulmonary Function Substudy (PulmENDS)
Substudy of Efficacy, Safety and Toxicology of Electronic Nicotine Delivery Systems as an Aid for Smoking Cessation (ESTxENDS): Pulmonary Function Substudy (PulmENDS)
--> This is a substudy of the main ESTxENDS trial (NCT03589989). Pulmonary function 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, e-cigarette 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. The inhaled ENDS aerosol appears safe in laboratory conditions, its long-term effects on pulmonary function remains unknown. This study will therefore investigate the impact of ENDS on lung function in smokers, who attempt to quit using ENDS compared with smokers, receiving only smoking cessation counseling with nicotine replacement therapy (NRT).
Multiple breath washout (MBW) is an established technique for assessment of peripheral airway function in pediatrics and its use is emerging in adult medicine, as it offers a better sensitivity to assess small airway disease before large airway involvement can be detected using conventional pulmonary function tests (PFT - spirometry, body plethysmography and diffusing capacity test). Preliminary evidence from limited studies suggest MBW parameters (LCI, Scond, Sacin) can be impaired in smokers with normal lung function and improve after smoking abstinence.
Primary objective of this substudy is to assess changes in LCI from baseline to 6 months post target quit date (TQD) in cigarette smokers randomized to the intervention group compared to the control group.
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 standard of care, i.e. smoking cessation counseling and encouragement to use NRT. Smoking cessation counseling will be provided in person at the first clinical visit and then over the phone at the target quit date and again at week 1, 2, 4 and 8 after the target quit date. Participants in the control group will receive only standard of care. All participants will be followed over a 6-month period. After 6 months, participants will be asked to come to a final clinical visit.
Study Overview
Status
Conditions
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
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Bern, Switzerland, 3010
- University Clinic for General Internal Medicine, Bern University Hospital
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Bern, Switzerland
- Department of Pneumology
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
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)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
|---|---|
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Experimental: Intervention group
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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 standards of care, i.e. smoking cessation counseling and encouragement to use NRT. Smoking cessation counseling will be provided in person at the first clinical visit and then over the phone at the target quit date and again at week 1, 2, 4 and 8 after the target quit date. All participants will be followed over a 6-month period. After 6 months, participants will be asked to come to a final clinical visit. PFT and MBW will be performed at baseline and after the 6 months follow-up period in all participants of the substudy. |
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Active Comparator: Control group
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Participants in the control group will receive standard of care only, i.e. i.e. smoking cessation counseling and encouragement to use NRT. Smoking cessation counseling will be provided in person at the first clinical visit and then over the phone at the target quit date and again at week 1, 2, 4 and 8 after the target quit date. All participants will be followed over a 6-month period. After 6 months, participants will be asked to come to a final clinical visit. PFT and MBW will be performed at baseline and after the 6 months follow-up period in all participants of the substudy. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Changes in Lung Clearance Index (LCI)
Time Frame: Change from baseline to 6 months post quit date
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Measured by multiple breath washout (MBW) of a tracer gas (N2).
LCI is defined as the cumulative expired volume/functional residual capacity (CEV/FRC) at 5% and 2.5% tracer gas concentration in the exhaled breath.
An LCI with a z-score < + 1.645 (upper limit of normal according to Singer F et al, PLoS One.
2012;7(4):e36083) is considered normal.
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Change from baseline to 6 months post quit date
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
|---|---|---|
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Lung Clearance Index (LCI)
Time Frame: 6 months post quit date
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Measured by multiple breath washout (MBW) of a tracer gas (N2).
LCI is defined as the cumulative expired volume/functional residual capacity (CEV/FRC) at 5% and 2.5% tracer gas concentration in the exhaled breath.
An LCI with a z-score < + 1.645 (upper limit of normal according to Singer F et al, PLoS One.
2012;7(4):e36083) is considered normal.
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6 months post quit date
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Changes in Scond and Sacin
Time Frame: Change from baseline to 6 months post quit date
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Measured by multiple breath washout (MBW).
MBW assesses ventilation of the peripheral airways.
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Change from baseline to 6 months post quit date
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Scond and Sacin
Time Frame: 6 months post quit date
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Measured by multiple breath washout (MBW).
MBW assesses ventilation of the peripheral airways.
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6 months post quit date
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Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: 6 months post quit date
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Measured by spirometry.
Spirometry is a conventional pulmonary function test measuring airflow.
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6 months post quit date
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Changes in Forced Expiratory Volume in 1 Second (FEV1)
Time Frame: Change from baseline to 6 months post quit date
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Measured by spirometry.
Spirometry is a conventional pulmonary function test measuring airflow.
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Change from baseline to 6 months post quit date
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Forced Expiratory Volume in 1 Second/Functional Vital Capacity Ratio (FEV1/FVC)
Time Frame: 6 months post quit date
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Measured by spirometry.
Spirometry is a conventional pulmonary function test measuring airflow.
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6 months post quit date
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Changes in Forced Expiratory Volume in 1 Second/Functional Vital Capacity Ratio (FEV1/FVC)
Time Frame: Change from baseline to 6 months post quit date
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Measured by spirometry.
Spirometry is a conventional pulmonary function test measuring airflow.
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Change from baseline to 6 months post quit date
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Total Lung Capacity (TLC)
Time Frame: 6 months post quit date
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Measured by body plethysmography.
Body plethysmography is a conventional pulmonary function test measuring lung volumes.
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6 months post quit date
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Changes in Total Lung Capacity (TLC)
Time Frame: Change from baseline to 6 months post quit date
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Measured by body plethysmography.
Body plethysmography is a conventional pulmonary function test measuring lung volumes.
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Change from baseline to 6 months post quit date
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Residual Volume (RV)
Time Frame: 6 months post quit date
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Measured by body plethysmography.
Body plethysmography is a conventional pulmonary function test measuring lung volumes.
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6 months post quit date
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Changes in Residual Volume (RV)
Time Frame: Change from baseline to 6 months post quit date
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Measured by body plethysmography.
Body plethysmography is a conventional pulmonary function test measuring lung volumes.
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Change from baseline to 6 months post quit date
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Residual Volume to Total Lung Capacity (RV/TLC)
Time Frame: 6 months post quit date
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Measured by body plethysmography.
Body plethysmography is a conventional pulmonary function test measuring lung volumes.
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6 months post quit date
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Changes in Residual Volume to Total Lung Capacity (RV/TLC)
Time Frame: Change from baseline to 6 months post quit date
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Measured by body plethysmography.
Body plethysmography is a conventional pulmonary function test measuring lung volumes.
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Change from baseline to 6 months post quit date
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Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)
Time Frame: 6 months post quit date
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Measured by diffusing capacity test.
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6 months post quit date
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Changes in Diffusing Capacity of the Lungs for Carbon Monoxide (DLCO)
Time Frame: Change from baseline to 6 months post quit date
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Measured by diffusing capacity test.
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Change from baseline to 6 months post quit date
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Fraction of exhaled nitric oxide (FeNO)
Time Frame: 6 months post quit date
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Measured by the levels of nitric oxide in the exhaled breath.
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6 months post quit date
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Changes in Fraction of exhaled nitric oxide (FeNO)
Time Frame: Change from baseline to 6 months post quit date
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Measured by the levels of nitric oxide in the exhaled breath.
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Change from baseline to 6 months post quit date
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Manuela Funke-Chambour, PD Dr. med., Inselspital Universität Bern
- Study Director: Reto Auer, Prof.Dr.med, Berner Institut für Hausarztmedizin; Universität Bern
Publications and helpful links
General Publications
- 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.
- Robinson PD, Latzin P, Verbanck S, Hall GL, Horsley A, Gappa M, Thamrin C, Arets HG, Aurora P, Fuchs SI, King GG, Lum S, Macleod K, Paiva M, Pillow JJ, Ranganathan S, Ratjen F, Singer F, Sonnappa S, Stocks J, Subbarao P, Thompson BR, Gustafsson PM. Consensus statement for inert gas washout measurement using multiple- and single- breath tests. Eur Respir J. 2013 Mar;41(3):507-22. doi: 10.1183/09031936.00069712. Epub 2013 Feb 8. Erratum In: Eur Respir J. 2013 Nov;42(5):1432. Ranganathan, Sarah [corrected to Ranganathan, Sarath].
- Subbarao P, Milla C, Aurora P, Davies JC, Davis SD, Hall GL, Heltshe S, Latzin P, Lindblad A, Pittman JE, Robinson PD, Rosenfeld M, Singer F, Starner TD, Ratjen F, Morgan W. Multiple-Breath Washout as a Lung Function Test in Cystic Fibrosis. A Cystic Fibrosis Foundation Workshop Report. Ann Am Thorac Soc. 2015 Jun;12(6):932-9. doi: 10.1513/AnnalsATS.201501-021FR. Erratum In: Ann Am Thorac Soc. 2017 Jan;14(1):145.
- Jetmalani K, Thamrin C, Farah CS, Bertolin A, Chapman DG, Berend N, Salome CM, King GG. Peripheral airway dysfunction and relationship with symptoms in smokers with preserved spirometry. Respirology. 2018 May;23(5):512-518. doi: 10.1111/resp.13215. Epub 2017 Nov 15.
- Verbanck S, Schuermans D, Meysman M, Paiva M, Vincken W. Noninvasive assessment of airway alterations in smokers: the small airways revisited. Am J Respir Crit Care Med. 2004 Aug 15;170(4):414-9. doi: 10.1164/rccm.200401-037OC. Epub 2004 May 6.
- Verbanck S, Schuermans D, Paiva M, Meysman M, Vincken W. Small airway function improvement after smoking cessation in smokers without airway obstruction. Am J Respir Crit Care Med. 2006 Oct 15;174(8):853-7. doi: 10.1164/rccm.200603-422OC. Epub 2006 Jun 23.
- Singer F, Houltz B, Latzin P, Robinson P, Gustafsson P. A realistic validation study of a new nitrogen multiple-breath washout system. PLoS One. 2012;7(4):e36083. doi: 10.1371/journal.pone.0036083. Epub 2012 Apr 27.
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 2017-02332h
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
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