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

June 4, 2025 updated by: Andrea Hobkirk, PhD, Milton S. Hershey Medical Center
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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
19

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Contact Backup

Study Locations

  • United States
    • Pennsylvania
      • Hershey, Pennsylvania, United States, 17033
        • Penn State Health

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

21 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Description

Inclusion Criteria:

  1. Aged 21-60
  2. Smoke filtered cigarettes/machine-rolled cigarettes (≥5 cigarettes per day) or daily e-cigarette use for past year.
  3. 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.
  4. Willing to supplement cigarette smoking with ECIG use for 4 weeks or replace e-cigarette with study product for 4 weeks
  5. Willing to attend regular visits over a 4-week period (not planning to move, not planning extended vacation, no planned surgeries)
  6. Willing to undergo two fMRI scans
  7. Able to read and write in English
  8. Able to understand and consent to study procedures
  9. Access to computer with internet service that allows for use of Zoom

Exclusion Criteria:

  1. Impaired smell function as measured via a standardized screening assessment
  2. 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)
  3. 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
  4. Women who are pregnant (verified by urine pregnancy test at any visit), trying to become pregnant, or nursing
  5. Medical conditions associated with cognitive impairment or neurological dysfunction
  6. Severe claustrophobia
  7. Current depressive or anxiety disorder
  8. Uncontrolled mental illness or substance abuse or inpatient treatment for these conditions in the past 6 months
  9. 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
  10. 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
  11. Known allergy to propylene glycol or vegetable glycerin
  12. Other member of household currently participating in the study
  13. History of a seizure disorder or had a seizure in the past 12 months
  14. 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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Other
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Quadruple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Placebo Comparator: 0mg/ml Tobacco Flavor ECIG
Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a tobacco flavor.
Other: Placebo ECIG with Tobacco Flavor
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.
Placebo Comparator: 0mg/ml Strawberry Vanilla Flavor ECIG
Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a strawberry vanilla flavor.
Other: Placebo ECIG with Strawberry Vanilla Flavor
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.
Experimental: 18mg/ml Tobacco Flavor ECIG
Participants will be provided with an ECIG containing 18mg/ml nicotine concentration and a tobacco flavor.
Other: Nicotine Containing ECIG with tobacco flavor
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.
Experimental: 18mg/ml Strawberry Vanilla Flavor ECIG
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
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Baseline Neural Flavor Cue-reactivity at Baseline
Time Frame: 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
Time Frame: 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.
Baseline to 4-weeks
Changes in Neural Flavor Cue-reactivity Across Flavor Groups
Time Frame: 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.
Baseline to 4-weeks

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
ECIG Dependence
Time Frame: 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.
2-weeks post-randomization to 4-weeks post-randomization
ECIG Liking and Satisfaction
Time Frame: 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.
2-weeks to 4-weeks
Craving to Smoke/Vape
Time Frame: 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.
Baseline to 4-weeks post-randomization

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Milton S. Hershey Medical Center

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute on Drug Abuse (NIDA)

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
November 4, 2019

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
April 30, 2024

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
April 30, 2024

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 4, 2019

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 4, 2019

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 8, 2019

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
June 22, 2025

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
June 4, 2025

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
June 1, 2025

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 11837
  • R03DA047582 (U.S. NIH Grant/Contract)

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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