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

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 Olfactory Function Substudy of ESTxENDS

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04617444
• Other study ID #: 2017-02332j
• Status: Completed
• Phase: N/A
• Start date: September 7, 2020
• 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). Olfactory function outcomes should be considered secondary outcomes of the main smoking cessation outcome formulated in NCT03589989.

Up to one in five people have suffered loss or impairment of their sense of smell, limiting their available information about the environment, including possible hazards (e.g. gas or smoke). An impaired sense of smell is strongly associated with smoking, but its prevalence in smokers has yet to be established. Since only a few prospective cohort studies among smokers have compared change in olfactory function in smokers, it is not known how much or how fast smoking may impair olfactory function. Some studies describe improvement in olfactory function among quitters, supporting anecdotal evidence from ex-smokers who say they regained their sense of smell over time. As far as the investigators know, no randomized controlled trial has tested the effects of a smoking cessation intervention on olfactory function.

A reliable and validated olfactory function test is the Burghart Sniffin' Sticks 16-item Identification-test, which is quick and easy to administer. 16 familiar odours will be presented to the participants, each for 3-4 seconds. After each odour the participant is asked to select the correct answer from 4 possible answers.

With increasing popularity of e-cigarettes, their effect on the olfactory function also needs to be assessed. It is known, that e-cigarettes produce toxic compounds such as carbonyl and aldehydes, what could impair the sense of smell - especially if the liquid-level is too low or the temperature on the coil is too hot. This is the source of a phenomenon called "dry-hit", which is said to leave a burnt taste or smell to be recognized by users. However, it is unclear if e-cigarettes users with an olfactory dysfunction can adequately recognize a "dry-hit". Therefore, the goal is to investigate the effects of smoking cessation and use of ENDS on olfactory function and the recognition of a "dry-hit" from a test e-cigarette.

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. The primary objective is to assess changes in olfactory function from baseline to 6 months post target quit date (TQD) in cigarette smokers randomized to the intervention group compared to the control group.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 389
• 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 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

Related Conditions & MeSH terms

• Olfactory Disorder
• 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 (15)

Ajmani GS, Suh HH, Wroblewski KE, Pinto JM. Smoking and olfactory dysfunction: A systematic literature review and meta-analysis. Laryngoscope. 2017 Aug;127(8):1753-1761. doi: 10.1002/lary.26558. Epub 2017 May 31. — View Citation

Dinc AS, Sengezer T, Cayonu M, Sahin MM. Smoking cessation improves olfactory functions. Laryngoscope. 2020 Feb;130(2):E35-E38. doi: 10.1002/lary.27992. Epub 2019 Apr 5. — View Citation

Doty RL, Kamath V. The influences of age on olfaction: a review. Front Psychol. 2014 Feb 7;5:20. doi: 10.3389/fpsyg.2014.00020. eCollection 2014. — View Citation

Farsalinos KE, Gillman G. Carbonyl Emissions in E-cigarette Aerosol: A Systematic Review and Methodological Considerations. Front Physiol. 2018 Jan 11;8:1119. doi: 10.3389/fphys.2017.01119. eCollection 2017. — View Citation

Farsalinos KE, Voudris V, Poulas K. E-cigarettes generate high levels of aldehydes only in 'dry puff' conditions. Addiction. 2015 Aug;110(8):1352-6. doi: 10.1111/add.12942. Epub 2015 May 20. — View Citation

Frye RE, Schwartz BS, Doty RL. Dose-related effects of cigarette smoking on olfactory function. JAMA. 1990 Mar 2;263(9):1233-6. — View Citation

Hummel T, Kobal G, Gudziol H, Mackay-Sim A. Normative data for the "Sniffin' Sticks" including tests of odor identification, odor discrimination, and olfactory thresholds: an upgrade based on a group of more than 3,000 subjects. Eur Arch Otorhinolaryngol. 2007 Mar;264(3):237-43. doi: 10.1007/s00405-006-0173-0. Epub 2006 Sep 23. — View Citation

Jung HJ, Shin IS, Lee JE. Olfactory function in mild cognitive impairment and Alzheimer's disease: A meta-analysis. Laryngoscope. 2019 Feb;129(2):362-369. doi: 10.1002/lary.27399. Epub 2018 Nov 22. — View Citation

Mullol J, Alobid I, Marino-Sanchez F, Quinto L, de Haro J, Bernal-Sprekelsen M, Valero A, Picado C, Marin C. Furthering the understanding of olfaction, prevalence of loss of smell and risk factors: a population-based survey (OLFACAT study). BMJ Open. 2012 Nov 6;2(6):e001256. doi: 10.1136/bmjopen-2012-001256. Print 2012. — View Citation

Neuland C, Bitter T, Marschner H, Gudziol H, Guntinas-Lichius O. Health-related and specific olfaction-related quality of life in patients with chronic functional anosmia or severe hyposmia. Laryngoscope. 2011 Apr;121(4):867-72. doi: 10.1002/lary.21387. Epub 2011 Feb 4. — View Citation

Rumeau C, Nguyen DT, Jankowski R. How to assess olfactory performance with the Sniffin' Sticks test((R)). Eur Ann Otorhinolaryngol Head Neck Dis. 2016 Jun;133(3):203-6. doi: 10.1016/j.anorl.2015.08.004. Epub 2015 Sep 4. — View Citation

Schubert CR, Cruickshanks KJ, Fischer ME, Huang GH, Klein BE, Klein R, Pankow JS, Nondahl DM. Olfactory impairment in an adult population: the Beaver Dam Offspring Study. Chem Senses. 2012 May;37(4):325-34. doi: 10.1093/chemse/bjr102. Epub 2011 Nov 1. — View Citation

Siegel JK, Wroblewski KE, McClintock MK, Pinto JM. Olfactory dysfunction persists after smoking cessation and signals increased cardiovascular risk. Int Forum Allergy Rhinol. 2019 Sep;9(9):977-985. doi: 10.1002/alr.22357. Epub 2019 Jul 31. — View Citation

Vennemann MM, Hummel T, Berger K. The association between smoking and smell and taste impairment in the general population. J Neurol. 2008 Aug;255(8):1121-6. doi: 10.1007/s00415-008-0807-9. Epub 2008 Jul 28. — View Citation

Whitcroft KL, Hummel T. Clinical Diagnosis and Current Management Strategies for Olfactory Dysfunction: A Review. JAMA Otolaryngol Head Neck Surg. 2019 Sep 1;145(9):846-853. doi: 10.1001/jamaoto.2019.1728. — View Citation

* Note: There are 15 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Assessment of olfactory function- Baseline	Assessment of olfactory function with the Burghart Sniffin' Sticks 16-item Identification-test. The highest possible score is 16; the cut-off for hyposmia is 11 and cut-off for anosmia is 8.	Baseline
Primary	Assessment of olfactory function- follow-up	Assessment of olfactory function with the Burghart Sniffin' Sticks 16-item Identification-test. The highest possible score is 16; the cut-off for hyposmia is 11 and cut-off for anosmia is 8.	6 months post quit date]
Secondary	Assessment of change of olfactory function	Assessment of change of olfactory function with the Burghart Sniffin' Sticks 16-item Identification-test. The highest possible score is 16; the cut-off for hyposmia is 11 and cut-off for anosmia is 8.	change from baseline to 6 months post quit date
Secondary	Assessment of dry-hit recognition	Assessment of dry-hit recognition. Participants will be given 2 ENDS to have them assess the probability of a dry-hit. The participants will be asked to rate the probability of a dry-hit in both ENDS as follows: Definitely (3 points); Probably (2 points); Probably not (1 points); Definitely not (0 points) 2 or 3 points will be interpreted as correctly identifying the ENDS generating a dry-hit.	6 months post quit date