Trial Outcomes & Findings for Establishing the Effect of Flavor on the Addictive Potential of Electronic Cigarettes (NCT NCT03905928)

NCT ID: NCT03905928

Last Updated: 2025-06-22

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

19 participants

Primary outcome timeframe

Baseline

Results posted on

2025-06-22

Participant Flow

Participant milestones

Participant milestones
Measure
18mg/ml Tobacco Flavor ECIG
Participants will be provided with an ECIG containing 18mg/ml nicotine concentration and a tobacco flavor.
0mg/ml Tobacco Flavor ECIG
Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a tobacco flavor.
18mg/ml Strawberry Vanilla Flavor ECIG
Participants will be provided with an ECIG containing 18mg/ml nicotine concentration and a strawberry vanilla flavor.
0mg/ml Strawberry Vanilla Flavor ECIG
Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a strawberry vanilla flavor.
Overall Study
STARTED
6
3
5
5
Overall Study
COMPLETED
5
3
3
4
Overall Study
NOT COMPLETED
1
0
2
1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
18mg/ml Tobacco Flavor ECIG
n=6 Participants
Participants will be provided with an ECIG containing 18mg/ml nicotine concentration and a tobacco flavor.
0mg/ml Tobacco Flavor ECIG
n=3 Participants
Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a tobacco flavor.
18mg/ml Strawberry Vanilla Flavor ECIG
n=5 Participants
Participants will be provided with an ECIG containing 18mg/ml nicotine concentration and a strawberry vanilla flavor.
0mg/ml Strawberry Vanilla Flavor ECIG
n=5 Participants
Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a strawberry vanilla flavor.
Total
n=19 Participants
Total of all reporting groups
Age, Continuous
49.00 years
STANDARD_DEVIATION 9.30 • n=93 Participants
41.67 years
STANDARD_DEVIATION 13.05 • n=4 Participants
45.60 years
STANDARD_DEVIATION 10.46 • n=27 Participants
44.40 years
STANDARD_DEVIATION 8.99 • n=483 Participants
46.00 years
STANDARD_DEVIATION 9.60 • n=36 Participants
Sex: Female, Male
Female
4 Participants
n=93 Participants
2 Participants
n=4 Participants
3 Participants
n=27 Participants
4 Participants
n=483 Participants
13 Participants
n=36 Participants
Sex: Female, Male
Male
2 Participants
n=93 Participants
1 Participants
n=4 Participants
2 Participants
n=27 Participants
1 Participants
n=483 Participants
6 Participants
n=36 Participants
Ethnicity (NIH/OMB)
Hispanic or Latino
0 Participants
n=93 Participants
0 Participants
n=4 Participants
1 Participants
n=27 Participants
0 Participants
n=483 Participants
1 Participants
n=36 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
6 Participants
n=93 Participants
3 Participants
n=4 Participants
4 Participants
n=27 Participants
5 Participants
n=483 Participants
18 Participants
n=36 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
0 Participants
n=483 Participants
0 Participants
n=36 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
n=93 Participants
1 Participants
n=4 Participants
0 Participants
n=27 Participants
0 Participants
n=483 Participants
1 Participants
n=36 Participants
Race (NIH/OMB)
Asian
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
0 Participants
n=483 Participants
0 Participants
n=36 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
0 Participants
n=483 Participants
0 Participants
n=36 Participants
Race (NIH/OMB)
Black or African American
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
0 Participants
n=483 Participants
0 Participants
n=36 Participants
Race (NIH/OMB)
White
6 Participants
n=93 Participants
2 Participants
n=4 Participants
5 Participants
n=27 Participants
5 Participants
n=483 Participants
18 Participants
n=36 Participants
Race (NIH/OMB)
More than one race
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
0 Participants
n=483 Participants
0 Participants
n=36 Participants
Race (NIH/OMB)
Unknown or Not Reported
0 Participants
n=93 Participants
0 Participants
n=4 Participants
0 Participants
n=27 Participants
0 Participants
n=483 Participants
0 Participants
n=36 Participants

PRIMARY outcome

Timeframe: Baseline

Population: For this within-subjects comparison of laboratory task conditions, we included all 19 participants who completed a functional MRI scan at baseline. All assigned groups were combined since group assignment was not a variable of interest for this aim.

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.

Outcome measures

Outcome measures
Measure
Total Baseline Sample
n=19 Participants
The total baseline sample includes the 19 participants who completed a functional MRI scan at baseline and were randomized to a condition, regardless of study completion.
0 mg/ml Nicotine Concentration E-cigarettes
This group includes participants randomized to the 0 mg/ml nicotine concentration e-cigarettes, regardless of flavor.
18mg/ml Strawberry Vanilla Flavor ECIG
Participants will be provided with an ECIG containing 15mg/ml nicotine concentration and a strawberry vanilla flavor.
0mg/ml Strawberry Vanilla Flavor ECIG
Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a strawberry vanilla flavor.
Baseline Neural Flavor Cue-reactivity at Baseline
Right insula
0.08 percentage of BOLD signal change
Standard Deviation 0.07
Baseline Neural Flavor Cue-reactivity at Baseline
Left amygdala
0.23 percentage of BOLD signal change
Standard Deviation 0.20
Baseline Neural Flavor Cue-reactivity at Baseline
Ventral tegmental area
0.10 percentage of BOLD signal change
Standard Deviation 0.07
Baseline Neural Flavor Cue-reactivity at Baseline
Left ventral cerebellum
0.14 percentage of BOLD signal change
Standard Deviation 0.12
Baseline Neural Flavor Cue-reactivity at Baseline
Right dorsal cerebellum
0.13 percentage of BOLD signal change
Standard Deviation 0.16
Baseline Neural Flavor Cue-reactivity at Baseline
Left dorsal cerebellum
0.09 percentage of BOLD signal change
Standard Deviation 0.07
Baseline Neural Flavor Cue-reactivity at Baseline
Medial prefrontal cortex
-0.15 percentage of BOLD signal change
Standard Deviation 0.13
Baseline Neural Flavor Cue-reactivity at Baseline
Left medial pre/postcentral gyri
-0.06 percentage of BOLD signal change
Standard Deviation 0.05
Baseline Neural Flavor Cue-reactivity at Baseline
Left lateral pre/postcentral gyri
-0.07 percentage of BOLD signal change
Standard Deviation 0.07
Baseline Neural Flavor Cue-reactivity at Baseline
Precuneous
-0.07 percentage of BOLD signal change
Standard Deviation 0.06
Baseline Neural Flavor Cue-reactivity at Baseline
Right pre/postcentral gyri
-0.06 percentage of BOLD signal change
Standard Deviation 0.04
Baseline Neural Flavor Cue-reactivity at Baseline
Bilateral superior frontal gyrus
-0.07 percentage of BOLD signal change
Standard Deviation 0.05

PRIMARY outcome

Timeframe: Baseline to 4-weeks

Population: This analysis includes 15 participants who completed baseline and post-intervention functional MRI scans. Groups assigned to nicotine vs. no nicotine were compared and flavor sub-groups within the nicotine groups (tobacco vs. strawberry) were combined, since flavor was not a variable of interest for this aim.

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.

Outcome measures

Outcome measures
Measure
Total Baseline Sample
n=8 Participants
The total baseline sample includes the 19 participants who completed a functional MRI scan at baseline and were randomized to a condition, regardless of study completion.
0 mg/ml Nicotine Concentration E-cigarettes
n=7 Participants
This group includes participants randomized to the 0 mg/ml nicotine concentration e-cigarettes, regardless of flavor.
18mg/ml Strawberry Vanilla Flavor ECIG
Participants will be provided with an ECIG containing 15mg/ml nicotine concentration and a strawberry vanilla flavor.
0mg/ml Strawberry Vanilla Flavor ECIG
Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a strawberry vanilla flavor.
Changes in Neural Flavor Cue-reactivity Across Nicotine Groups
Left insula
0.18 % BOLD signal change difference score
Standard Deviation 0.17
-0.12 % BOLD signal change difference score
Standard Deviation 0.15
Changes in Neural Flavor Cue-reactivity Across Nicotine Groups
Medial prefrontal cortex
0.21 % BOLD signal change difference score
Standard Deviation 0.14
-0.21 % BOLD signal change difference score
Standard Deviation 0.29

PRIMARY outcome

Timeframe: Baseline to 4-weeks

Population: This analysis includes 15 participants who completed baseline and post-intervention functional MRI scans. Groups assigned to tobacco vs. strawberry were compared and nicotine sub-groups within the flavor groups (nicotine vs. no nicotine) were combined, since nicotine was not a variable of interest for this aim.

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.

Outcome measures

Outcome measures
Measure
Total Baseline Sample
n=8 Participants
The total baseline sample includes the 19 participants who completed a functional MRI scan at baseline and were randomized to a condition, regardless of study completion.
0 mg/ml Nicotine Concentration E-cigarettes
n=7 Participants
This group includes participants randomized to the 0 mg/ml nicotine concentration e-cigarettes, regardless of flavor.
18mg/ml Strawberry Vanilla Flavor ECIG
Participants will be provided with an ECIG containing 15mg/ml nicotine concentration and a strawberry vanilla flavor.
0mg/ml Strawberry Vanilla Flavor ECIG
Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a strawberry vanilla flavor.
Changes in Neural Flavor Cue-reactivity Across Flavor Groups
Right prefrontal cortex
-0.07 % BOLD signal change difference score
Standard Deviation 0.03
0.05 % BOLD signal change difference score
Standard Deviation 0.05
Changes in Neural Flavor Cue-reactivity Across Flavor Groups
Thalamus and right insula
-0.05 % BOLD signal change difference score
Standard Deviation 0.01
0.06 % BOLD signal change difference score
Standard Deviation 0.06

SECONDARY outcome

Timeframe: 2-weeks post-randomization to 4-weeks post-randomization

Population: This analysis included 14 participants who completed the 2-week check-in and 4-week post-intervention visits and completed the PSECDI.

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.

Outcome measures

Outcome measures
Measure
Total Baseline Sample
n=5 Participants
The total baseline sample includes the 19 participants who completed a functional MRI scan at baseline and were randomized to a condition, regardless of study completion.
0 mg/ml Nicotine Concentration E-cigarettes
n=3 Participants
This group includes participants randomized to the 0 mg/ml nicotine concentration e-cigarettes, regardless of flavor.
18mg/ml Strawberry Vanilla Flavor ECIG
n=2 Participants
Participants will be provided with an ECIG containing 15mg/ml nicotine concentration and a strawberry vanilla flavor.
0mg/ml Strawberry Vanilla Flavor ECIG
n=4 Participants
Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a strawberry vanilla flavor.
ECIG Dependence
-1.60 units on a scale
Standard Deviation 2.07
-1.33 units on a scale
Standard Deviation 3.21
-3.00 units on a scale
Standard Deviation 4.24
0.00 units on a scale
Standard Deviation 1.41

SECONDARY outcome

Timeframe: 2-weeks to 4-weeks

Population: This analysis includes 8 participants who completed the e-cigarette evaluation scale at the 2-week check-in and 4-week post-intervention visit. Only participants who reported using the study e-cigarette since the last study visit completed the evaluation scale.

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.

Outcome measures

Outcome measures
Measure
Total Baseline Sample
n=3 Participants
The total baseline sample includes the 19 participants who completed a functional MRI scan at baseline and were randomized to a condition, regardless of study completion.
0 mg/ml Nicotine Concentration E-cigarettes
n=1 Participants
This group includes participants randomized to the 0 mg/ml nicotine concentration e-cigarettes, regardless of flavor.
18mg/ml Strawberry Vanilla Flavor ECIG
n=1 Participants
Participants will be provided with an ECIG containing 15mg/ml nicotine concentration and a strawberry vanilla flavor.
0mg/ml Strawberry Vanilla Flavor ECIG
n=3 Participants
Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a strawberry vanilla flavor.
ECIG Liking and Satisfaction
2.33 units on a scale
Standard Deviation 7.57
-21.00 units on a scale
Standard Deviation 0.00
16 units on a scale
Standard Deviation 0.00
-5.00 units on a scale
Standard Deviation 4.36

SECONDARY outcome

Timeframe: Baseline to 4-weeks post-randomization

Population: This analysis includes 15 participants that completed the craving scales before the functional MRI scans at baseline and at the post-intervention visits.

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.

Outcome measures

Outcome measures
Measure
Total Baseline Sample
n=5 Participants
The total baseline sample includes the 19 participants who completed a functional MRI scan at baseline and were randomized to a condition, regardless of study completion.
0 mg/ml Nicotine Concentration E-cigarettes
n=3 Participants
This group includes participants randomized to the 0 mg/ml nicotine concentration e-cigarettes, regardless of flavor.
18mg/ml Strawberry Vanilla Flavor ECIG
n=3 Participants
Participants will be provided with an ECIG containing 15mg/ml nicotine concentration and a strawberry vanilla flavor.
0mg/ml Strawberry Vanilla Flavor ECIG
n=4 Participants
Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a strawberry vanilla flavor.
Craving to Smoke/Vape
3.00 units on a scale
Standard Deviation 5.43
3.00 units on a scale
Standard Deviation 5.43
-11.00 units on a scale
Standard Deviation 2.65
1.50 units on a scale
Standard Deviation 4.43

Adverse Events

18mg/ml Tobacco Flavor ECIG

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

0mg/ml Tobacco Flavor ECIG

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

18mg/ml Strawberry Vanilla Flavor ECIG

Serious events: 0 serious events
Other events: 1 other events
Deaths: 0 deaths

0mg/ml Strawberry Vanilla Flavor ECIG

Serious events: 0 serious events
Other events: 2 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure
18mg/ml Tobacco Flavor ECIG
n=6 participants at risk
Participants will be provided with an ECIG containing 18mg/ml nicotine concentration and a tobacco flavor.
0mg/ml Tobacco Flavor ECIG
n=3 participants at risk
Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a tobacco flavor.
18mg/ml Strawberry Vanilla Flavor ECIG
n=5 participants at risk
Participants will be provided with an ECIG containing 18mg/ml nicotine concentration and a strawberry vanilla flavor.
0mg/ml Strawberry Vanilla Flavor ECIG
n=5 participants at risk
Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a strawberry vanilla flavor.
Respiratory, thoracic and mediastinal disorders
Throat irritation
0.00%
0/6 • 4 weeks
0.00%
0/3 • 4 weeks
0.00%
0/5 • 4 weeks
20.0%
1/5 • Number of events 1 • 4 weeks
Surgical and medical procedures
Procedure
0.00%
0/6 • 4 weeks
0.00%
0/3 • 4 weeks
0.00%
0/5 • 4 weeks
20.0%
1/5 • Number of events 1 • 4 weeks
Respiratory, thoracic and mediastinal disorders
Flu-like symptoms
0.00%
0/6 • 4 weeks
0.00%
0/3 • 4 weeks
20.0%
1/5 • Number of events 1 • 4 weeks
0.00%
0/5 • 4 weeks

Additional Information

Andrea Hobkirk

Pennsylvania State University College of Medicine

Phone: 717-531-7279

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place