Tobacco Dependence
Conditions
Keywords
smoking, electronic cigarettes, flavor, cue-reactivity
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.
Interventions
OTHERNicotine 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.
OTHERNicotine 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.
OTHERPlacebo 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.
OTHERPlacebo 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.
Sponsors
National Institute on Drug Abuse (NIDA)
Milton S. Hershey Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
OTHER
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
21 Years to 60 Years
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 18mg/ml Tobacco Flavor ECIG Participants will be provided with an ECIG containing 18mg/ml nicotine concentration and a tobacco flavor. | 6 |
| 0mg/ml Tobacco Flavor ECIG Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a tobacco flavor. | 3 |
| 18mg/ml Strawberry Vanilla Flavor ECIG Participants will be provided with an ECIG containing 18mg/ml nicotine concentration and a strawberry vanilla flavor. | 5 |
| 0mg/ml Strawberry Vanilla Flavor ECIG Participants will be provided with an ECIG containing 0mg/ml nicotine concentration and a strawberry vanilla flavor. | 5 |
| Total | 19 |
Baseline characteristics
| Characteristic | 18mg/ml Strawberry Vanilla Flavor ECIG | 0mg/ml Strawberry Vanilla Flavor ECIG | 18mg/ml Tobacco Flavor ECIG | 0mg/ml Tobacco Flavor ECIG | Total |
|---|---|---|---|---|---|
| Age, Continuous | 45.60 years STANDARD_DEVIATION 10.46 | 44.40 years STANDARD_DEVIATION 8.99 | 49.00 years STANDARD_DEVIATION 9.3 | 41.67 years STANDARD_DEVIATION 13.05 | 46.00 years STANDARD_DEVIATION 9.6 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 0 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 4 Participants | 5 Participants | 6 Participants | 3 Participants | 18 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants | 1 Participants | 1 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 5 Participants | 5 Participants | 6 Participants | 2 Participants | 18 Participants |
| Sex: Female, Male Female | 3 Participants | 4 Participants | 4 Participants | 2 Participants | 13 Participants |
| Sex: Female, Male Male | 2 Participants | 1 Participants | 2 Participants | 1 Participants | 6 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk | EG002 affected / at risk | EG003 affected / at risk |
|---|---|---|---|---|
| deaths Total, all-cause mortality | 0 / 6 | 0 / 3 | 0 / 5 | 0 / 5 |
| other Total, other adverse events | 0 / 6 | 0 / 3 | 1 / 5 | 2 / 5 |
| serious Total, serious adverse events | 0 / 6 | 0 / 3 | 0 / 5 | 0 / 5 |
Outcome results
Primary
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total Baseline Sample | Baseline Neural Flavor Cue-reactivity at Baseline | Right insula | 0.08 percentage of BOLD signal change | Standard Deviation 0.07 |
| Total Baseline Sample | Baseline Neural Flavor Cue-reactivity at Baseline | Left amygdala | 0.23 percentage of BOLD signal change | Standard Deviation 0.2 |
| Total Baseline Sample | Baseline Neural Flavor Cue-reactivity at Baseline | Ventral tegmental area | 0.10 percentage of BOLD signal change | Standard Deviation 0.07 |
| Total Baseline Sample | Baseline Neural Flavor Cue-reactivity at Baseline | Left ventral cerebellum | 0.14 percentage of BOLD signal change | Standard Deviation 0.12 |
| Total Baseline Sample | Baseline Neural Flavor Cue-reactivity at Baseline | Right dorsal cerebellum | 0.13 percentage of BOLD signal change | Standard Deviation 0.16 |
| Total Baseline Sample | Baseline Neural Flavor Cue-reactivity at Baseline | Left dorsal cerebellum | 0.09 percentage of BOLD signal change | Standard Deviation 0.07 |
| Total Baseline Sample | Baseline Neural Flavor Cue-reactivity at Baseline | Medial prefrontal cortex | -0.15 percentage of BOLD signal change | Standard Deviation 0.13 |
| Total Baseline Sample | Baseline Neural Flavor Cue-reactivity at Baseline | Left medial pre/postcentral gyri | -0.06 percentage of BOLD signal change | Standard Deviation 0.05 |
| Total Baseline Sample | Baseline Neural Flavor Cue-reactivity at Baseline | Left lateral pre/postcentral gyri | -0.07 percentage of BOLD signal change | Standard Deviation 0.07 |
| Total Baseline Sample | Baseline Neural Flavor Cue-reactivity at Baseline | Precuneous | -0.07 percentage of BOLD signal change | Standard Deviation 0.06 |
| Total Baseline Sample | Baseline Neural Flavor Cue-reactivity at Baseline | Right pre/postcentral gyri | -0.06 percentage of BOLD signal change | Standard Deviation 0.04 |
| Total Baseline Sample | Baseline Neural Flavor Cue-reactivity at Baseline | Bilateral superior frontal gyrus | -0.07 percentage of BOLD signal change | Standard Deviation 0.05 |
Comparison: This was a whole-brain, voxel-wise general linear model conducted in FSL software using a one-sample t-test on the tobacco\>strawberry condition contrasts conducted at the subject-level.
Primary
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total Baseline Sample | Changes in Neural Flavor Cue-reactivity Across Flavor Groups | Right prefrontal cortex | -0.07 % BOLD signal change difference score | Standard Deviation 0.03 |
| Total Baseline Sample | 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 mg/ml Nicotine Concentration E-cigarettes | Changes in Neural Flavor Cue-reactivity Across Flavor Groups | Right prefrontal cortex | 0.05 % BOLD signal change difference score | Standard Deviation 0.05 |
| 0 mg/ml Nicotine Concentration E-cigarettes | Changes in Neural Flavor Cue-reactivity Across Flavor Groups | Thalamus and right insula | 0.06 % BOLD signal change difference score | Standard Deviation 0.06 |
Comparison: This was a whole-brain, voxel-wise repeated measures ANOVA conducted using FSL software on activation from baseline to post-intervention between the flavor groups (tobacco vs. strawberry) for the tobacco\>strawberry condition contrasts calculated at the subject-level. The means and standard deviations presented are the average post-pre scan difference scores of the BOLD percentage signal change of tobacco \> strawberry contrasts for each group.
Primary
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.
Time frame: 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.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Total Baseline Sample | Changes in Neural Flavor Cue-reactivity Across Nicotine Groups | Left insula | 0.18 % BOLD signal change difference score | Standard Deviation 0.17 |
| Total Baseline Sample | Changes in Neural Flavor Cue-reactivity Across Nicotine Groups | Medial prefrontal cortex | 0.21 % BOLD signal change difference score | Standard Deviation 0.14 |
| 0 mg/ml Nicotine Concentration E-cigarettes | Changes in Neural Flavor Cue-reactivity Across Nicotine Groups | Left insula | -0.12 % BOLD signal change difference score | Standard Deviation 0.15 |
| 0 mg/ml Nicotine Concentration E-cigarettes | Changes in Neural Flavor Cue-reactivity Across Nicotine Groups | Medial prefrontal cortex | -0.21 % BOLD signal change difference score | Standard Deviation 0.29 |
Comparison: This was a whole-brain, voxel-wise repeated measures ANOVA conducted using FSL software on activation from baseline to post-intervention that differ by the nicotine groups (18 mg/ml vs. 0 mg/ml) for the tobacco\>strawberry condition contrasts calculated at the subject-level. The means and standard deviations presented are the average post-pre scan difference scores of the BOLD percentage signal change of tobacco \> strawberry contrasts for each group.
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Total Baseline Sample | Craving to Smoke/Vape | 3.00 units on a scale | Standard Deviation 5.43 |
| 0 mg/ml Nicotine Concentration E-cigarettes | Craving to Smoke/Vape | 3.00 units on a scale | Standard Deviation 5.43 |
| 18mg/ml Strawberry Vanilla Flavor ECIG | Craving to Smoke/Vape | -11.00 units on a scale | Standard Deviation 2.65 |
| 0mg/ml Strawberry Vanilla Flavor ECIG | Craving to Smoke/Vape | 1.50 units on a scale | Standard Deviation 4.43 |
Comparison: We conducted a one-way ANOVA to compare changes in self-reported craving across all groups.p-value: 0.022ANOVA
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Total Baseline Sample | ECIG Dependence | -1.60 units on a scale | Standard Deviation 2.07 |
| 0 mg/ml Nicotine Concentration E-cigarettes | ECIG Dependence | -1.33 units on a scale | Standard Deviation 3.21 |
| 18mg/ml Strawberry Vanilla Flavor ECIG | ECIG Dependence | -3.00 units on a scale | Standard Deviation 4.24 |
| 0mg/ml Strawberry Vanilla Flavor ECIG | ECIG Dependence | 0.00 units on a scale | Standard Deviation 1.41 |
Comparison: We conducted a one-way ANOVA to compare the change in e-cigarette dependence (week 4 - week 2 PSECDI difference score) between the four e-cigarette groups.p-value: 0.573ANOVA
Secondary
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.
Time frame: 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.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Total Baseline Sample | ECIG Liking and Satisfaction | 2.33 units on a scale | Standard Deviation 7.57 |
| 0 mg/ml Nicotine Concentration E-cigarettes | ECIG Liking and Satisfaction | -21.00 units on a scale | Standard Deviation 0 |
| 18mg/ml Strawberry Vanilla Flavor ECIG | ECIG Liking and Satisfaction | 16 units on a scale | Standard Deviation 0 |
| 0mg/ml Strawberry Vanilla Flavor ECIG | ECIG Liking and Satisfaction | -5.00 units on a scale | Standard Deviation 4.36 |