Tobacco DependenceNCT03905928
Establishing the Effect of Flavor on the Addictive Potential of Electronic Cigarettes
A study testing Nicotine Containing ECIG with tobacco flavor and Nicotine Containing ECIG with Strawberry Vanilla Flavor in people with Tobacco Dependence, run by Milton S. Hershey Medical Center at 1 site in United States.
Trial 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. Read more about this study
- Who is it for?
- Ages 21 to 60 yearsHealthy volunteers can take part
- Conditions the study is for
- Tobacco Dependence
- What is being tested?
- Nicotine Containing ECIG with tobacco flavor and Nicotine Containing ECIG with Strawberry Vanilla Flavor
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 19 participants
- Where
- 1 siteUnited States
- Study dates
- 4 Nov 2019to 30 Apr 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 21 to 60 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- 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
Show all 9Show fewer
- 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
Who cannot join
- 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
Show all 14Show fewer
- 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
Trial locations and contacts
1 site in 1 country.
About this study
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
- Being tested
- Nicotine Containing ECIG with tobacco flavor, Nicotine Containing ECIG with Strawberry Vanilla Flavor, Placebo ECIG with Tobacco Flavor, Placebo ECIG with Strawberry Vanilla Flavor
- Keywords
- smoking, electronic cigarettes, flavor, cue-reactivity
- Medical subject headings
- Tobacco Use Disorder, Smoking, Vaping
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Nicotine Containing ECIG with tobacco flavorOther
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.
Nicotine Containing ECIG with Strawberry Vanilla FlavorOther
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.
Placebo ECIG with Tobacco FlavorOther
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 ECIG with Strawberry Vanilla FlavorOther
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.
| Study group | Role | What they receive |
|---|---|---|
| 18mg/ml Tobacco Flavor ECIG | Experimental | Participants will be provided with an ECIG containing 18mg/ml nicotine concentration and a tobacco flavor. Receives: 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. Receives: 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. Receives: 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. Receives: Other: Placebo ECIG with Strawberry Vanilla Flavor |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 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.
Measured: 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.
Measured: Baseline to 4-weeks
Secondary outcomes (3)
ECIG Dependence
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.
Measured: 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. 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.
Measured: 2-weeks to 4-weeks
Craving to Smoke/Vape
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.
Measured: Baseline to 4-weeks post-randomization
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Apr 2019
- Study start4 Nov 2019
- Primary completion30 Apr 2024
- Study completion30 Apr 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Tobacco DependenceStudies of the same condition, open and under way.
- More trials run by Milton S. Hershey Medical CenterThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 19 participants (actual)
Sponsor and investigators
- Lead sponsor
- Milton S. Hershey Medical Center
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Responsible party
- Principal investigator, Andrea Hobkirk, PhD, Milton S. Hershey Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03905928
- Sponsor's protocol ID
- 11837
- Other IDs
- R03DA047582
- Status last verified
- Jun 2025
- First submitted
- 4 Apr 2019
- Last updated
- 22 Jun 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 22 Jun 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Establishing the Effect of Flavor on the Addictive Potential of Electronic Cigarettes
- ClinicalTrials.gov ID
- NCT03905928
- Acronym / sponsor ID
- 11837
- Conditions
- Tobacco Dependence
- Keywords
- smoking, electronic cigarettes, flavor, cue-reactivity
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 19 participants (actual)
- Lead sponsor
- Milton S. Hershey Medical CenterUniversity, hospital or other
- Collaborators
- National Institute on Drug Abuse (NIDA)
- Study start
- 4 Nov 2019 (actual)
- Primary completion
- 30 Apr 2024 (actual)
- Study completion
- 30 Apr 2024 (actual)
- First posted
- 8 Apr 2019 (actual)
- Results
- Posted 22 Jun 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Other
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 18mg/ml Tobacco Flavor ECIG | Experimental | Other: Nicotine Containing ECIG with tobacco flavorParticipants will be provided with an ECIG containing 18mg/ml nicotine concentration and a tobacco flavor. |
| 0mg/ml Tobacco Flavor ECIG | Placebo comparator | Other: Placebo ECIG with Tobacco FlavorParticipants will be provided with an ECIG containing 0mg/ml nicotine concentration and a tobacco flavor. |
| 18mg/ml Strawberry Vanilla Flavor ECIG | Experimental | Other: Nicotine Containing ECIG with Strawberry Vanilla FlavorParticipants will be provided with an ECIG containing 18mg/ml nicotine concentration and a strawberry vanilla flavor. |
| 0mg/ml Strawberry Vanilla Flavor ECIG | Placebo comparator | Other: Placebo ECIG with Strawberry Vanilla FlavorParticipants will be provided with an ECIG containing 0mg/ml nicotine concentration and a strawberry vanilla flavor. |
Who may qualify
- Ages
- 21 to 60 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (9 listed)
- 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)
Key exclusion criteria (14 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Nicotine Containing ECIG with tobacco flavorParticipants 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. | Other | 18mg/ml Tobacco Flavor ECIG |
| Nicotine Containing ECIG with Strawberry Vanilla FlavorParticipants 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. | Other | 18mg/ml Strawberry Vanilla Flavor ECIG |
| Placebo ECIG with Tobacco FlavorParticipants 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. | Other | 0mg/ml Tobacco Flavor ECIG |
| Placebo ECIG with Strawberry Vanilla FlavorParticipants 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. | Other | 0mg/ml Strawberry Vanilla Flavor ECIG |
Primary outcome
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.
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.
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.
3 secondary outcomes
ECIG Dependence
Time frame: 2-weeks post-randomization to 4-weeks post-randomization
ECIG Liking and Satisfaction
Time frame: 2-weeks to 4-weeks
Craving to Smoke/Vape
Time frame: Baseline to 4-weeks post-randomization
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Jun 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Nicotine Containing ECIG with tobacco flavor and Nicotine Containing ECIG with Strawberry Vanilla Flavor in people with Tobacco Dependence, run by Milton S. Hershey Medical Center at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 9 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 22 Jun 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 22 Jun 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Baseline Neural Flavor Cue-reactivity at Baseline (time frame: Baseline). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 22 Jun 2025.