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

Study Overview
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Brief Summary
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--> 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.

Official Title
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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

Conditions
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Smoking Cessation, Olfactory Disorder

Intervention / Treatment
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* Other: ENDS (vaporizer/e-cig) and smoking cessation counseling
* Other: Smoking cessation counseling


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Intervention group<br> | Other: ENDS (vaporizer/e-cig) and smoking cessation counseling<br>* 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.<br>|
| Active Comparator: Control group<br> | Other: Smoking cessation counseling<br>* 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.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 
| 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 |