Effect of E-Liquid Flavor on Respiratory Symptoms in People Using Electronic Nicotine Delivery Systems

Study Overview
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Brief Summary
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This is a randomized, parallel-group open-label trial to evaluate respiratory symptoms in ENDS users switching from banned flavors to a non-banned flavor (tobacco) or 'tobacco free' nicotine pouches.

Official Title
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A Randomized, Parallel-group Open-label Trial of ENDS Users Switching From Flavors of Potentially High-toxicity Profile to Flavors of Potentially Low-toxicity Profile (CRoFT_3.2)

Conditions
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Electronic Cigarette Use

Intervention / Treatment
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* Other: E-cigarette Flavor
* Other: Tobacco Free Nicotine Pouch


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: ENDS users as determined by: (a) using banned flavored ENDS with nicotine such as fruit, candy, dessert flavors, and/or any product that indicates such flavors (b) using ENDS daily, regularly for the past 6 months (self-reported). No smoking tobacco or using smokeless tobacco for the past 6 months. Subjects should be free of acute respiratory illness within the proceeding 30 days prior to recruitment (self-reported). Participant must understand the investigational nature of this study and sign an Independent Ethics Committee/Institutional Review Board approved written informed consent form prior to receiving any study related procedure. After receiving information regarding the NYS flavor ban individuals must not want to quit vaping or stop using their flavored product for the next 90 days. Exclusion Criteria: Individuals with health conditions and therapies that may affect immune responses and levels of inflammatory markers, including allergic rhinitis, aspirin/NSAID therapy, asthma, immunodeficiency (HIV or other), Guillain-Barre Syndrome, COPD, or fever/respiratory illness within 30 days prior to entry into study (self-reported). Pregnant or nursing female participants (self-reported on telephone screener, pregnancy test on Visit#1) Unable to communicate in English. Unable or unwilling to follow protocol requirements. Self-report having active, untreated medical/psychiatric conditions. History of serious side effects from nicotine or from any nicotine replacement therapies. Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection, symptomatic congestive heart failure, unstable angina pectoris, cardiac arrhythmia, or psychiatric illness/social situations that would limit compliance with study requirements Vulnerable populations, such as cognitively impaired adults, individuals who are not yet adults, pregnant women, and prisoners. Any condition which in the Investigator's opinion deems the participant an unsuitable candidate to receive study drug. After receiving information about the NYS flavor ban, participants who report that they are thinking about quitting or stop using their flavor within the next 90 days.

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 55 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: Use Own Brand of Flavored Product<br>Participants will use their current flavor of e cigarettes for 90 days | Other: E-cigarette Flavor<br>* Participants use an electronic nicotine delivery system with an assigned tobacco-flavored e-liquid<br>|
| Experimental: Use Provided Tobacco Flavor<br>Participants will use a new assigned flavor for 90 days | Other: E-cigarette Flavor<br>* Participants use an electronic nicotine delivery system with an assigned tobacco-flavored e-liquid<br>|
| Active Comparator: Vaping Abstinence - use Tobacco Free Nicotine Pouches<br>Participants will be asked to stop vaping for 90 days and instead only use the provided 'tobacco free' nicotine pouches. | Other: Tobacco Free Nicotine Pouch<br>* participants will use tobacco free oral nicotine pouches<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Risk biomarkers of inflammation and oxidative stress as measured by ELISA | Oxidative stress and inflammation in plasma using ELISA . A quantitative measure of expression (units:pg/mg) will be produced. | Up to 90 days | 
| Respiratory tract inflammation activity | Exhaled Nitric Oxide (FeNo)l be measured in participants' breath using a FDA cleared monitor NIOX VERO (Aerocrine) according to ATS guidelines. FeNO has been used to monitor airway inflammation to account for persistent and/or high allergen exposure as a factor associated with higher levels of FeNO | Up to 90 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Amount of recent flavored product use | Assessed using the PhenX Toolkit which tracks tobacco use and asks subjects to retrospectively estimate product use, | UP to 90 days | 
| Flavor Preference questionnaire | Personal flavor questionnaire to determine flavor preference when using ENDS. | Up to 90 days | 
| Frequency of flavored product use | Questions from Wave 1 Adult PATH Survey to measure use and regularity of use flavored products | Up to 90 days |