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

Not Applicable

Completed

Conditions: Tobacco Dependence

Registration Number: NCT03905928

Lead Sponsor: Milton S. Hershey Medical Center

Brief Summary: 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.

Detailed Description: Not available

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 19

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

Study & Design

Study Type: INTERVENTIONAL

Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Baseline Neural Flavor Cue-reactivity at Baseline	Baseline	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. The means reported are the average percentage of BOLD signal change between the fMRI task odor conditions (tobacco vs. strawberry) identified using a whole-brain one-sample t-test with FSL software. Positive values indicate stronger BOLD signal during tobacco odor cues and negative values indicate stronger BOLD signal during strawberry odor cues.
Changes in Neural Flavor Cue-reactivity Across Nicotine Groups	Baseline to 4-weeks	Functional magnetic resonance imaging (fMRI) will be used to measure changes in blood oxygen-level dependent (BOLD) signal for the tobacco\>strawberry contrast across 18 mg/ml vs. 0 mg/ml nicotine concentration groups from baseline to 4-weeks post-randomization using a whole-brain repeated measures ANOVA with FSL software. The means reported are the difference (4-week post-intervention - baseline) of the average percentage of BOLD signal change between the fMRI task odor conditions (tobacco vs. strawberry). Positive values indicate increases in tobacco\>strawberry BOLD signal and negative values indicate decreases in tobacco\> strawberry BOLD signal.
Changes in Neural Flavor Cue-reactivity Across Flavor Groups	Baseline to 4-weeks	Functional magnetic resonance imaging (fMRI) will be used to measure changes in blood oxygen-level dependent (BOLD) signal for the tobacco \> strawberry contrast across flavor groups (tobacco vs. strawberry) from baseline to 4-weeks post-randomization. The means reported are the difference (4-week post-intervention - baseline) of the average percentage of BOLD signal change between the fMRI task odor condition (tobacco vs. strawberry) identified using a whole-brain repeated measures ANOVA with FSL software. Positive values indicate increases in tobacco\>strawberry BOLD signal and negative values indicate decreases in tobacco\> strawberry BOLD signal.

Secondary Outcome Measures

Name	Time	Method
ECIG Dependence	2-weeks post-randomization to 4-weeks post-randomization	Changes in self-reported ECIG dependence will be measured using the Penn State Electronic Cigarette Dependence Index (PSECDI). Total scores on this 10-item measure range from 0 to 20, with higher scores indicating higher levels of e-cigarette dependence. The means reported here are the week 4 - week 2 difference scores of the total dependence score. Positive means indicate increases in e-cigarette dependence, while negative means indicated decreases in e-cigarette dependence.
ECIG Liking and Satisfaction	2-weeks to 4-weeks	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. The means reported here are the difference of the total scores at week 4 - week 2, with positive means indicating increases in e-cigarette liking and negative means indicating decreases in liking. Note that standard deviation cannot be reported for groups with only one participant.
Craving to Smoke/Vape	Baseline to 4-weeks post-randomization	Changes in self-reported craving to smoke/vape were measured with 3 questions on amount, intensity, and self-control using visual analogue scales ranging from 0 to 10 prior to completing the functional MRI scan. Total scores range from 0 to 30 and higher scores indicate more craving. The means reported here are week 4 post-intervention - baseline difference scores of the total craving score. Positive means indicate increases in craving, while negative means indicate decreases in craving.