Effects of Novel E-cigarette Constituents on Adults TCORS 3.0

Study Overview
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Brief Summary
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This study is an examination of the influence of cooling components of WS-3 and menthol on the appeal and addiction potential of nicotine-containing e-liquids among adults.

Detailed Description
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The investigators will examine the influence of cooling components of WS-3 (a synthetic coolant) and menthol on the appeal and addiction potential of nicotine-containing e-liquids among adults. Participants will rate the flavor intensity, coolness, sweetness, and irritation/harshness, bitterness experienced using validated rating scales. 66 adult participants (18+ years of age) who are current e-cigarette users will participate in 3 laboratory sessions. Participants will receive 3 e-cigarette that contain cooling flavors and nicotine (59mg/ml nicotine salt) during the sessions. Participants will be randomized to receive one of the 3 menthol conditions (no-menthol, low menthol, high menthol) in combination three WS-3 conditions (no WS-3, low WS-3, high WS-3). All participants will be exposed to all nine conditions across 3 lab sessions.

Official Title
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Examining Appeal and Addiction Potential of Novel E-cigarette Constituents Among Adults

Conditions
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Nicotine Use Disorder

Intervention / Treatment
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* Other: E-liquid coolant (no WS-3) (1)
* Other: E-liquid coolant (Low WS-3) (1)
* Other: E-liquid coolant (High WS-3) (1)
* Other: E-liquid coolant (no WS-3) (2)
* Other: E-liquid coolant (Low WS-3) (2)
* Other: E-liquid coolant (High WS-3) (2)
* Other: E-liquid coolant (no WS-3) (3)
* Other: E-liquid coolant (Low WS-3) (3)
* Other: E-liquid coolant (High WS-3) (3)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: 18 years or older Able to read and write Some current e-cigarette use Willing to abstain from tobacco/nicotine use 2 hours prior to sessions Exclusion Criteria: Current use of non-prescription substances besides nicotine, marijuana, alcohol Any significant current medical or psychiatric condition Known hypersensitivity to propylene glycol Pregnant or lactating females Uncontrolled asthma Nut/e-liquid flavorant allergy Current marijuana (tetrahydrocannabinol) vaping + E-cigarette or vaping use Associated Lung Injury (EVALI) symptoms

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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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: Crossover Assignment
Interventional Model Description: All participants receive all 9 study conditions.
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Non-menthol, nicotine 59mg/ml (1)<br>Flavor without menthol with 59mg/ml nicotine | Other: E-liquid coolant (no WS-3) (1)<br>* Adult users of e-cigarette will be exposed to distinct e-liquid coolants without WS-3.<br>* Other names: Flavor type;|
| Experimental: Low menthol, nicotine 59mg/ml (1)<br>Flavor with low menthol concentration with 59mg/ml nicotine | Other: E-liquid coolant (Low WS-3) (1)<br>* Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.<br>* Other names: Flavor type;|
| Experimental: High menthol, nicotine 59mg/ml (1)<br>Flavor with high menthol concentration with 59mg/ml nicotine | Other: E-liquid coolant (High WS-3) (1)<br>* Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.<br>* Other names: Flavor type;|
| Experimental: Non-menthol, nicotine 59mg/ml (2)<br>Flavor without menthol with 59mg/ml nicotine | Other: E-liquid coolant (Low WS-3) (2)<br>* Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.<br>* Other names: Flavor type;|
| Experimental: Low menthol, nicotine 59mg/ml (2)<br>Flavor with low menthol concentration with 59mg/ml nicotine | Other: E-liquid coolant (no WS-3) (2)<br>* Adult users of e-cigarette will be exposed to distinct e-liquid coolants without WS-3.<br>* Other names: Flavor type;|
| Experimental: High menthol, nicotine 59mg/ml (2)<br>Flavor with high menthol concentration with 59mg/ml nicotine | Other: E-liquid coolant (Low WS-3) (3)<br>* Adult users of e-cigarette will be exposed to distinct e-liquid coolants with low WS-3 concentration.<br>* Other names: Flavor type;|
| Experimental: Non-menthol, nicotine 59mg/ml (3)<br>Flavor without menthol with 59mg/ml nicotine | Other: E-liquid coolant (High WS-3) (2)<br>* Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.<br>* Other names: Flavor type;|
| Experimental: Low menthol, nicotine 59mg/ml (3)<br>Flavor with low menthol concentration with 59mg/ml nicotine | Other: E-liquid coolant (High WS-3) (3)<br>* Adult users of e-cigarette will be exposed to distinct e-liquid coolants with high WS-3 concentration.<br>* Other names: Flavor type;|
| Experimental: High menthol, nicotine 59mg/ml (3)<br>Flavor with high menthol concentration with 59mg/ml nicotine | Other: E-liquid coolant (no WS-3) (3)<br>* Adult users of e-cigarette will be exposed to distinct e-liquid coolants without WS-3.<br>* Other names: Flavor type;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Liking: Score change in liking/wanting of each e-cigarette condition (3 conditions in total) | The Labeled Hedonic Scale will be used to ask about liking and wanting of the e-cigarette (one item Visual Analog Scale with ratings ranging from most disliked sensation imaginable to most liked sensation imaginable with higher values indicating greater liking). | Following administration of e-cigarette condition 1 (at 10 minutes), following administration of e-cigarette condition 2 (at 40 minutes), following administration of e-cigarette condition 3 (at 70 minutes) | 
| Reinforcing Efficacy: Score change in drug effects of each e-cigarette condition (3 conditions in total) | Difference between e-cigarette effects for each e-cigarette condition as measured by the computerized version of the Drug Effects Questionnaire (DEQ). Participants will self-report their responses using a computer mouse to indicate where on the scale response falls. A modified version of the Drug Effects Questionnaire (DEQ) will be used in which participants rate acute responses to the e-cigarette on a 0-100mm scale from not at all (0mm) to extremely (100mm). | Following administration of e-cigarette condition 1 (at 10 minutes), following administration of e-cigarette condition 2 (at 40 minutes), following administration of e-cigarette condition 3 (at 70 minutes) | 
| Irritation/Harshness: Score change in irritation of harshness of each e-cigarette condition (3 conditions in total) | Difference in irritation at each e-cigarette condition as measured by the computerized Generalized Labeled Magnitude Scale (gLMS). Participants will self-report their responses using a computer mouse to indicate where on the scale response falls. The Generalized Labeled Magnitude Scales (gLMS) are category ratio scales with seven semantic labels: no sensation, barely detectable, weak, moderate, strong, very strong, and strongest imaginable, positioned quasi-logarithmically as per empirically determined semantic magnitudes on a 0-100 scale (strongest imaginable at the 100 end). | Following administration of e-cigarette condition 1 (at 10 minutes), following administration of e-cigarette condition 2 (at 40 minutes), following administration of e-cigarette condition 3 (at 70 minutes) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Craving: Change in craving score for e-cigarette from baseline at each e-cigarette condition (3 conditions in total) | Difference from baseline in craving for each e-cigarette condition will be measured by the Generalized Labeled Magnitude Scale (gLMS). Participants will self-report their craving for e cigarettes using a computer mouse to indicate where on the scale response falls. The Generalized Labeled Magnitude Scales (gLMS) are category ratio scales with seven semantic labels: no sensation, barely detectable, weak, moderate, strong, very strong, and strongest imaginable, positioned quasi-logarithmically as per empirically determined semantic magnitudes on a 0-100 scale (strongest imaginable at the 100 end). | At baseline (at 0 minute), following administration of e-cigarette condition 1 (at 10 minutes), following administration of e-cigarette condition 2 (at 40 minutes), following administration of e-cigarette condition 3 (at 70 minutes) | 
| Changes of salivary Nicotine and Cotinine Levels from baseline at each e-cigarette condition (3 conditions in total) | Saliva samples will be collected following each exposure to product and before each lab sessions to assess change in nicotine/cotinine levels. These levels will be used for correlational analyses with behavioral measures and will be determined using LC/MS techniques at the core laboratory of university. | At baseline (at 0 minute), Following administration of e-cigarette condition 1 (at 10 minutes), following administration of e-cigarette condition 2 (at 40 minutes), following administration of e-cigarette condition 3 (at 70 minutes) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Menthol, cooling components, cigarette, e-cigarette, vaping