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

NCT03905928 | Completed Results

• 2 other identifiers: 11837R03DA047582
• Study Type: interventional
• Target: 19
• Locations: 1 country
• Sites: 1

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.

Conditions

Tobacco Dependence

Keywords

smoking; electronic cigarettes; flavor; cue-reactivity

Outcome Measures

Primary Outcomes (3)

• Baseline Neural Flavor Cue-reactivity at 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.

  Baseline

• Changes in Neural Flavor Cue-reactivity Across Nicotine Groups

  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.

  Baseline to 4-weeks

• Changes in Neural Flavor Cue-reactivity Across Flavor Groups

  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.

  Baseline to 4-weeks

Secondary Outcomes (3)

• ECIG Dependence

  2-weeks post-randomization to 4-weeks post-randomization

• ECIG Liking and Satisfaction

  2-weeks to 4-weeks

• Craving to Smoke/Vape

  Baseline to 4-weeks post-randomization

Study Arms (4)

18mg/ml Tobacco Flavor ECIG

EXPERIMENTAL

Participants will be provided with an ECIG containing 18mg/ml nicotine concentration and a tobacco flavor.

Other: Nicotine Containing ECIG with tobacco flavor

0mg/ml Tobacco Flavor ECIG

PLACEBO COMPARATOR

Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a tobacco flavor.

Other: Placebo ECIG with Tobacco Flavor

18mg/ml Strawberry Vanilla Flavor ECIG

EXPERIMENTAL

Participants will be provided with an ECIG containing 18mg/ml nicotine concentration and a strawberry vanilla flavor.

Other: Nicotine Containing ECIG with Strawberry Vanilla Flavor

0mg/ml Strawberry Vanilla Flavor ECIG

PLACEBO COMPARATOR

Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a strawberry vanilla flavor.

Other: Placebo ECIG with Strawberry Vanilla Flavor

Interventions

Nicotine Containing ECIG with tobacco flavor OTHER

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.

18mg/ml Tobacco Flavor ECIG

Nicotine Containing ECIG with Strawberry Vanilla Flavor OTHER

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.

18mg/ml Strawberry Vanilla Flavor ECIG

Placebo ECIG with Tobacco Flavor OTHER

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.

0mg/ml Tobacco Flavor ECIG

Placebo ECIG with Strawberry Vanilla Flavor OTHER

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.

0mg/ml Strawberry Vanilla Flavor ECIG

Eligibility Criteria

• Age: 21 Years - 60 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Milton S. Hershey Medical Center: lead
• National Institute on Drug Abuse (NIDA): collaborator

Study Sites (1)

Penn State Health

Hershey, Pennsylvania, 17033, United States

Location

MeSH Terms

Conditions

Tobacco Use Disorder; Smoking; Vaping

Condition Hierarchy (Ancestors)

Substance-Related Disorders; Chemically-Induced Disorders; Mental Disorders; Behavior

Limitations and Caveats

Results of brain activation reported here are average values of the percentage of blood-oxygen level-dependent signal change (tobacco vs. strawberry task odor conditions) extracted after conducting whole-brain, voxel-wise general linear models with FSL software. The sample size was too small to conduct some planned between-group analyses and significance thresholds were increased for some analyses.

Results Point of Contact

• Title: Andrea Hobkirk
• Organization: Pennsylvania State University College of Medicine

alh98@psu.edu

717-531-7279

Publication Agreements

• PI is Sponsor Employee: Yes
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: OTHER
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Assitant Professor

Study Record Dates

• First Submitted: April 4, 2019
• First Posted: April 8, 2019
• Study Start: November 4, 2019
• Primary Completion: April 30, 2024
• Study Completion: April 30, 2024
• Last Updated: June 22, 2025
• Results First Posted: June 22, 2025

Record last verified: 2025-06

Locations

US (1)