Tobacco Dependence
Conditions
Keywords
Tobacco, Nicotine, Smoking, Functional magnetic resonance imaging, Addiction
Brief summary
The overall goal of this study is to determine if switching to very low nicotine content cigarettes changes the function of brain circuitry involved in incentive salience and executive control among dependent smokers.
Detailed description
In a double-blind, randomized controlled trial, dependent smokers will be randomized to a 6-week very low nicotine content (VLNC) cigarette condition (N=50) or a 6-week normal nicotine content cigarette control condition (NNC; N=25). Participants will undergo functional magnetic resonance imaging (fMRI) scans at baseline and 6-weeks to investigate the nicotine-related modulation of brain circuitry involved in incentive salience valuation and executive control. Imaging tasks will engage the incentive salience of smoking cues and non-smoking rewards and executive control functions to identify changes in functional activity within, and effective connectivity between, known salience and executive control brain circuitry. A novel fMRI task using specialized odor presentation equipment and fMRI sequences will assess neural cue reactivity to smoke odors.
Interventions
Very low nicotine content cigarettes
Normal nicotine content cigarettes
Sponsors
National Institute on Drug Abuse (NIDA)
Milton S. Hershey Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
HEALTH_SERVICES_RESEARCH
Masking
DOUBLE (Subject, Investigator)
Masking description
Double-blind
Intervention model description
Randomized
Eligibility
Sex/Gender
ALL
Age
21 Years to 60 Years
Healthy volunteers
No
Inclusion criteria
* 21-60 years old * Smoke \>5 cigarettes per day * \>1 year of daily smoking * No quit attempt in prior month and not planning to quit smoking within next 3 months * Able to understand and consent to study procedures * High school or lower educational attainment or annual household income \< $50,000 * Plan to live in local area next 3 months * Women not pregnant or nursing and taking steps to avoid pregnancy * Able to read and write in English * Access to computer with internet service that allows for Zoom
Exclusion criteria
* Use of non-cigarette tobacco products in the past 7 days * Use of illicit substances more than once a week in the past 3 months (excluding marijuana) * Current alcohol abuse impairing participation * MRI safety contraindications (e.g., metal implants, claustrophobia) * Unstable or significant medical conditions (e.g., chronic obstructive pulmonary disorder, coronary heart disease) * Major neurological conditions or brain trauma * Major surgeries planned in next 3 months * Use of smoking cessation medication in prior month (e.g., varenicline, patch) * Uncontrolled serious mental illness, suicidality, or inpatient psychiatric hospitalization in the past 6 months * Unwillingness to provide urine samples * Unwilling to smoke study assigned cigarettes for the remainder of the trial * Plans to move or take extended travel out of the area in the next 3 months * Any other condition or situation that would, in the investigator's opinion, make it unlikely that the participant could comply with the study protocol * Self-reported color blindness * Left-handedness * Smell dysfunction as determined via standardized assessment
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Blood Oxygen Level Dependent (BOLD) Signal Collected by Functional Magnetic Resonance Imaging (fMRI) During Monetary Delay Discounting Task | Change in BOLD signal from baseline to the 6-week visit. | Change from baseline to 6-weeks post-intervention in percentage of BOLD signal during hard vs. no choice conditions on a monetary delay discounting task in a left-sided cortical brain region encompassing the central opercular and dorsolateral prefrontal cortices. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Change in Self-reported Cigarettes Per Day | Average cigarettes per day during week 1 subtracted from average cigarettes per day during week 6. | Difference in week 6 mean minus week 1 mean of cigarettes used per day reported by participants on daily logs. |
| Change in Percentage of Immediate Choices on Monetary Delay Discounting Task | Changes from baseline to 6-weeks post intervention. | A difference score (6-weeks minus baseline) of the percentage of trials where the immediate (vs. delayed) monetary option was chosen out of all task trials during the monetary delay discounting task that was completed outside of the MRI scan. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Very Low Nicotine Content Cigarettes Research cigarettes with very low nicotine content (0.03 mg/cigarette) compared to usual brand cigarettes. | 21 |
| Normal Nicotine Content Cigarettes Research cigarettes with normal nicotine content (0.8 mg/cigarette) similar to usual brand cigarettes. | 13 |
| Total | 34 |
Baseline characteristics
| Characteristic | Very Low Nicotine Content Cigarettes | Normal Nicotine Content Cigarettes | Total |
|---|---|---|---|
| Age, Continuous | 42.90 years STANDARD_DEVIATION 7.98 | 44.46 years STANDARD_DEVIATION 8.69 | 43.50 years STANDARD_DEVIATION 8.29 |
| Cigarette Dependence | 4.10 units on a scale STANDARD_DEVIATION 1.22 | 3.77 units on a scale STANDARD_DEVIATION 1.09 | 3.97 units on a scale STANDARD_DEVIATION 1.17 |
| Cigarettes per day (CPD) | 18.90 cigarettes per day STANDARD_DEVIATION 7.35 | 14.46 cigarettes per day STANDARD_DEVIATION 5.39 | 17.21 cigarettes per day STANDARD_DEVIATION 7.01 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 20 Participants | 13 Participants | 33 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Menthol vs Non-Menthol Menthol | 15 Participants | 6 Participants | 21 Participants |
| Menthol vs Non-Menthol Non-Menthol | 6 Participants | 7 Participants | 13 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 1 Participants | 1 Participants | 2 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 20 Participants | 12 Participants | 32 Participants |
| Region of Enrollment United States | 21 participants | 13 participants | 34 participants |
| Sex: Female, Male Female | 15 Participants | 8 Participants | 23 Participants |
| Sex: Female, Male Male | 6 Participants | 5 Participants | 11 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 13 |
| other Total, other adverse events | 1 / 21 | 1 / 13 |
| serious Total, serious adverse events | 0 / 21 | 0 / 13 |
Outcome results
Primary
Change in Blood Oxygen Level Dependent (BOLD) Signal Collected by Functional Magnetic Resonance Imaging (fMRI) During Monetary Delay Discounting Task
Change from baseline to 6-weeks post-intervention in percentage of BOLD signal during hard vs. no choice conditions on a monetary delay discounting task in a left-sided cortical brain region encompassing the central opercular and dorsolateral prefrontal cortices.
Time frame: Change in BOLD signal from baseline to the 6-week visit.
Population: Only participants who completed the baseline and post-randomization laboratory visits were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Very Low Nicotine Content Cigarettes | Change in Blood Oxygen Level Dependent (BOLD) Signal Collected by Functional Magnetic Resonance Imaging (fMRI) During Monetary Delay Discounting Task | 0.13 Percent change | Standard Deviation 0.18 |
| Normal Nicotine Content Cigarettes | Change in Blood Oxygen Level Dependent (BOLD) Signal Collected by Functional Magnetic Resonance Imaging (fMRI) During Monetary Delay Discounting Task | -0.16 Percent change | Standard Deviation 0.18 |
p-value: <0.00195% CI: [0.14, 0.43]t-test, 2 sided
Secondary
Change in Percentage of Immediate Choices on Monetary Delay Discounting Task
A difference score (6-weeks minus baseline) of the percentage of trials where the immediate (vs. delayed) monetary option was chosen out of all task trials during the monetary delay discounting task that was completed outside of the MRI scan.
Time frame: Changes from baseline to 6-weeks post intervention.
Population: Participants who completed both trial laboratory visits were included in the analysis.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Very Low Nicotine Content Cigarettes | Change in Percentage of Immediate Choices on Monetary Delay Discounting Task | 0.20 Change in percentage | Standard Deviation 30.26 |
| Normal Nicotine Content Cigarettes | Change in Percentage of Immediate Choices on Monetary Delay Discounting Task | 1.57 Change in percentage | Standard Deviation 9.16 |
p-value: 0.8995% CI: [-21.57, 18.82]t-test, 2 sided
Secondary
Change in Self-reported Cigarettes Per Day
Difference in week 6 mean minus week 1 mean of cigarettes used per day reported by participants on daily logs.
Time frame: Average cigarettes per day during week 1 subtracted from average cigarettes per day during week 6.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Very Low Nicotine Content Cigarettes | Change in Self-reported Cigarettes Per Day | -5.1 Number of cigarettes per day | Standard Deviation 7.9 |
| Normal Nicotine Content Cigarettes | Change in Self-reported Cigarettes Per Day | 3.3 Number of cigarettes per day | Standard Deviation 16 |
p-value: 0.06395% CI: [-17.24, 0.48]t-test, 2 sided