Effects of E-cigs vs Pouches on Cigarette Smoking and Addiction

Study Overview
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Brief Summary
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The study will recruit an anticipated 256 adults who currently smoke cigarettes and report a willingness to try switching to alternative, non-combustible products. Participants will be randomized to receive either e-cigarettes or nicotine pouches for a duration of 4 weeks and to 1 of 4 possible regulatory scenarios within products where flavor availability is either menthol and tobacco/unflavored available or tobacco/unflavored only available, and nicotine concentration is either higher (5% e-cig, 6mg pouch) or lower (2.4% e-cig, 3mg pouch). Participants will return for bi-weekly research visits (in person or remote videocall) to complete measures for study aims. Participants will complete a final follow-up at Week 6 to assess maintenance of cigarette reduction and willingness to continue using products once they are no longer provided. The investigators expect to observe which products and constituents lead to greater smoking reduction.

Detailed Description
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The study includes 5 visit and assessments over 6 weeks. The intake visit will take approximately 60 minutes and subsequent visits will take approximately 30 minutes. The study is proposed to run for 5 years.

Official Title
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Evaluating The Effects Of E-cigarettes Versus Oral Nicotine Pouches and Product Constituents (Menthol Flavor, Nicotine Concentration) On Adult Cigarette Smoking and Addiction

Conditions
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Smoking, Smoking Behaviors, Nicotine Dependence

Intervention / Treatment
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* Behavioral: E-cigarette with 2.4% Nicotine with Menthol and Tobacco Flavors
* Behavioral: E-cigarette with 2.4% Nicotine with Tobacco Flavor Only
* Behavioral: E-cigarette with 5% Nicotine with Menthol and Tobacco Flavors
* Behavioral: E-cigarette with 5% Nicotine with Tobacco Flavor Only
* Behavioral: Tobacco Pouches with 3mg Nicotine with Menthol and Tobacco Flavors
* Behavioral: Tobacco Pouches with 3mg Nicotine with Tobacco Flavor Only
* Behavioral: Tobacco Pouches with 6mg Nicotine with Menthol and Tobacco Flavors
* Behavioral: Tobacco Pouches with 6mg Nicotine with Tobacco Flavor Only


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 21+ years old English literate Currently smoking cigarettes, biochemically confirmed Not planning a smoking cessation attempt or to use smoking cessation pharmacotherapies (NRT, bupropion, varenicline) in the next month. Exclusion Criteria: Currently using any smoking cessation services and/or pharmacotherapies Currently pregnant or breastfeeding Significant current medical or psychiatric condition Known hypersensitivity to propylene glycol.

Ages Eligible for Study
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Minimum Age: 21 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: E-cigarettes<br>Adults who smoke cigarettes will be randomized to receive e-cigarettes for a duration of 4 weeks and to 1 of 4 possible regulatory scenarios within products where flavor availability is either menthol and tobacco/unflavored available or tobacco/unflavored only available, and nicotine concentration is either higher (5% e-cig) or lower (2.4% e-cig). Participants will return for bi-weekly research visits (in person or remote videocall) to complete measures for study aims. They will complete a final follow-up at Week 6 to assess maintenance of cigarette reduction and willingness to continue using products once they are no longer provided. | Behavioral: E-cigarette with 2.4% Nicotine with Menthol and Tobacco Flavors<br>* Flavor availability is menthol and tobacco/unflavored with lower nicotine concentration.<br>Behavioral: E-cigarette with 2.4% Nicotine with Tobacco Flavor Only<br>* Flavor availability is tobacco/unflavored only with lower nicotine concentration.<br>Behavioral: E-cigarette with 5% Nicotine with Menthol and Tobacco Flavors<br>* Flavor availability is menthol and tobacco/unflavored with higher nicotine concentration.<br>Behavioral: E-cigarette with 5% Nicotine with Tobacco Flavor Only<br>* Flavor availability is tobacco/unflavored only with higher nicotine concentration.<br>|
| Experimental: Nicotine Pouches<br>Adults who smoke cigarettes will be randomized to receive nicotine pouches for a duration of 4 weeks and to 1 of 4 possible regulatory scenarios within products where flavor availability is either menthol and tobacco/unflavored available or tobacco/unflavored only available, and nicotine concentration is either higher (6mg pouch) or lower (3mg pouch). Participants will return for bi-weekly research visits (in person or remote videocall) to complete measures for study aims. They will complete a final follow-up at Week 6 to assess maintenance of cigarette reduction and willingness to continue using products once they are no longer provided. | Behavioral: Tobacco Pouches with 3mg Nicotine with Menthol and Tobacco Flavors<br>* Flavor availability is menthol and tobacco/unflavored with lower nicotine concentration.<br>Behavioral: Tobacco Pouches with 3mg Nicotine with Tobacco Flavor Only<br>* Flavor availability is tobacco/unflavored only with lower nicotine concentration.<br>Behavioral: Tobacco Pouches with 6mg Nicotine with Menthol and Tobacco Flavors<br>* Flavor availability is menthol and tobacco/unflavored with higher nicotine concentration.<br>Behavioral: Tobacco Pouches with 6mg Nicotine with Tobacco Flavor Only<br>* Flavor availability is tobacco/unflavored only with higher nicotine concentration.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aim 1: Average number of cigarettes smoked per day | Participants will report the total number of cigarettes consumed each day using a well-validated timeline follow-back (TLFB) interview method to assess number of cigarettes smoked per day continuously over the 4-week observational period for each product condition. | From baseline to week 4 | 
| Aim 2: Percent of days using non-combustible product | Participants will report daily use of e-cigarettes or nicotine pouches using a well-validated timeline follow-back (TLFB) interview method continuously over the 4-week observational period to determine the total percent days use of the non-combustible product for each product condition. | From baseline to week 4 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Aim 1: Percent of days abstinent from cigarettes | Participants will report the total number of cigarettes consumed each day using a well-validated timeline follow-back (TLFB) interview method to assess number of cigarettes smoked per day continuously over the 4-week observational period to determine the total percent days abstinent (smoke-free) for each product condition. | From baseline to week 4 | 
| Aim 1: Biochemically verified 7 day point-prevalent abstinence from cigarettes | Complete switching from cigarettes will be assessed at the end of the study period using self-reported TLFB methods and biochemical verification with expired breath carbon monoxide (CO) testing (CO < 5ppm) to determine rates of 7-day point-prevalent abstinence | Week 4 | 
| Aim 1: Cigarette Dependence | Cigarette dependence will be measured using the 4-item PROMIS® Short Form v1.0 - Smoking Nicotine Dependence for All Smokers 4a. Each item is scored from 1-5 with the range of scores from 4-20 with higher scores representing greater cigarette dependence. | From baseline to week 4 | 
| Aim 2: Average use of non-combustible products per day | Participants will report daily e-cigarette and nicotine pouch quantity and frequency consumed using a well-validated timeline follow-back (TLFB) interview method to use continuously over the 4-week observational period for each product condition. | From baseline to week 4 | 
| Aim 2: Continued use of non-combustible products | Participants will report daily use of e-cigarettes or nicotine pouches using a well-validated timeline follow-back (TLFB) interview method to determine the total percent days use of the non-combustible product for each product condition during the follow-up period. | Week 4 to 6 |