Establishing the Effect of Flavor on the Addictive Potential of Electronic Cigarettes

Study Overview
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Brief Summary
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The current study aims to establish proof-of-concept that neural cue-reactivity can serve as an early, objective marker of electronic cigarette (ECIG) addictive potential. Further, this study will examine the effect of flavor and nicotine concentration on the addictive potential of ECIGs to aid research informing U.S. Food and Drug Administration (FDA) flavor regulations and smoking cessation.

Official Title
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Establishing the Effect of Flavor on the Addictive Potential of Electronic Cigarettes

Conditions
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Tobacco Dependence

Intervention / Treatment
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* Other: Nicotine Containing ECIG with tobacco flavor
* Other: Nicotine Containing ECIG with Strawberry Vanilla Flavor
* Other: Placebo ECIG with Tobacco Flavor
* Other: Placebo ECIG with Strawberry Vanilla Flavor


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Aged 21-60 Smoke filtered cigarettes/machine-rolled cigarettes (≥5 cigarettes per day) or daily e-cigarette use for past year. No serious quit attempt in prior month. This includes use of any FDA approved smoking cessation medication (varenicline, bupropion [used specifically as a quitting aid], patch, gum, lozenge, inhaler, and nasal spray) in the past 1 month as an indication of treatment seeking. Willing to supplement cigarette smoking with ECIG use for 4 weeks or replace e-cigarette with study product for 4 weeks Willing to attend regular visits over a 4-week period (not planning to move, not planning extended vacation, no planned surgeries) Willing to undergo two fMRI scans Able to read and write in English Able to understand and consent to study procedures Access to computer with internet service that allows for use of Zoom Exclusion Criteria: Impaired smell function as measured via a standardized screening assessment Unstable or significant medical condition in the past 12 months (recent heart attack or some other heart conditions, stroke, severe angina including high blood pressure) Severe immune system disorders (uncontrolled Human Immunodeficiency virus infection; unstable multiple sclerosis symptoms), respiratory diseases (exacerbations of asthma or chronic obstructive pulmonary disorder, require oxygen, require oral prednisone), kidney (dialysis) or liver diseases (cirrhosis), or any medical disorder/medication that may affect participant safety or biomarker data Women who are pregnant (verified by urine pregnancy test at any visit), trying to become pregnant, or nursing Medical conditions associated with cognitive impairment or neurological dysfunction Severe claustrophobia Current depressive or anxiety disorder Uncontrolled mental illness or substance abuse or inpatient treatment for these conditions in the past 6 months Use of illicit drugs or prescription drugs for non-medical use daily/almost daily or weekly in the past 3 months per National Institute on Drug Abuse (NIDA) Quick Screen, not including use of marijuana Any known risk from exposure to high-field strength magnetic fields (e.g., cardiac pacemakers), any irremovable metallic foreign objects in their body (e.g., braces), or a questionable history of metallic fragments which are likely to create artifact on the MRI scans Known allergy to propylene glycol or vegetable glycerin Other member of household currently participating in the study History of a seizure disorder or had a seizure in the past 12 months Currently taking medications prescribed to prevent seizures (such as Carbamazepine or Phenobarbital). Using seizure medications for off-label use (indications other than treatment for seizures) will not be included as an exclusion, these will be assessed on a case-by-case basis

Ages Eligible for Study
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Minimum Age: 21 Years
Maximum Age: 60 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: Other
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: 18mg/ml Tobacco Flavor ECIG<br>Participants will be provided with an ECIG containing 15mg/ml nicotine concentration and a tobacco flavor. | Other: Nicotine Containing ECIG with tobacco flavor<br>* Participants will be provided with an EGO style ECIG to be used for 28 days. The EGO style ECIG is a vape pen-style device that comprises of a rechargeable battery and a tank containing liquid. Those in this intervention group will receive an ECIG with 18mg/ml nicotine concentration and a tobacco flavor.<br>|
| Placebo Comparator: 0mg/ml Tobacco Flavor ECIG<br>Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a tobacco flavor. | Other: Placebo ECIG with Tobacco Flavor<br>* Participants will be provided with an EGO style ECIG to be used for 28 days. The EGO style ECIG is a vape pen-style device that comprises of a rechargeable battery and a tank containing liquid. Those in this intervention group will receive an ECIG with 0mg/ml nicotine concentration and a tobacco flavor.<br>|
| Experimental: 18mg/ml Strawberry Vanilla Flavor ECIG<br>Participants will be provided with an ECIG containing 15mg/ml nicotine concentration and a strawberry vanilla flavor. | Other: Nicotine Containing ECIG with Strawberry Vanilla Flavor<br>* Participants will be provided with an EGO style ECIG to be used for 28 days. The EGO style ECIG is a vape pen-style device that comprises of a rechargeable battery and a tank containing liquid. Those in this intervention group will receive an ECIG with 18mg/ml nicotine concentration and a strawberry vanilla flavor.<br>|
| Placebo Comparator: 0mg/ml Strawberry Vanilla Flavor ECIG<br>Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a strawberry vanilla flavor. | Other: Placebo ECIG with Strawberry Vanilla Flavor<br>* Participants will be provided with an EGO style ECIG to be used for 28 days. The EGO style ECIG is a vape pen-style device that comprises of a rechargeable battery and a tank containing liquid. Those in this intervention group will receive an ECIG with 0mg/ml nicotine concentration and a strawberry vanilla flavor.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Baseline neural flavor cue-reactivity | Functional magnetic resonance imaging (fMRI) will be used to measure blood oxygen-level dependent (BOLD) signal in response to tobacco vs. strawberry-vanilla ECIG flavors at baseline. BOLD signal in functional circuits involved in reward processing, expectancies, and craving are of primary interest, including the ventral striatum, ACC, amygdala, lateral and medial PFC, OFC, and insula. | Baseline | 
| Changes in neural flavor cue-reactivity | Functional magnetic resonance imaging (fMRI) will be used to measure changes in blood oxygen-level dependent (BOLD) signal in response to 18 mg/ml vs. 0 mg/ml nicotine concentrations from baseline to 4-weeks post-randomization. BOLD signal in functional circuits involved in reward processing, expectancies, and craving are of primary interest, including the ventral striatum, ACC, amygdala, lateral and medial PFC, OFC, and insula. | Baseline to 4-weeks | 
| Changes in neural flavor cue-reactivity | Functional magnetic resonance imaging (fMRI) will be used to measure changes in blood oxygen-level dependent (BOLD) signal in response to assigned vs. un-assigned flavors from baseline to 4-weeks post-randomization. BOLD signal in functional circuits involved in reward processing, expectancies, and craving are of primary interest, including the ventral striatum, ACC, amygdala, lateral and medial PFC, OFC, and insula. | Baseline to 4-weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| ECIG dependence | Changes in self-reported ECIG dependence will be measured using the Penn State Electronic Cigarette Dependence Index. Total scores on this 10-item measure range from 0 to 20, with higher scores indicating higher levels of dependence. | 2-weeks post-randomization to 4-weeks post-randomization | 
| ECIG liking and satisfaction | Changes in subjective experiences of ECIG use related to liking and satisfaction will be collected via a self-report survey. The survey consists of 21-items (7-reversed scored) with response options on a 7-point likert scale and total scores ranging from 0 to 126. Higher scores indicate more ECIG liking and satisfaction. | Baseline to 4-weeks | 
| ECIG craving | Changes in self-reported ECIG craving will be measured with 3 questions on amount, intensity, and self-control during a state of nicotine withdrawal using visual analogue scales ranging from 0 to 10. Total scores range from 0 to 30 and higher scores indicate more craving. | 2-weeks post-randomization to 4-weeks post-randomization | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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smoking, electronic cigarettes, flavor, cue-reactivity