Nicotine Dependence
Conditions
Keywords
transcranial magnetic stimulation, fMRI, cue craving
Brief summary
Cigarette smoking causes significant morbidity and mortality in the United States. Smoking cessation is difficult, with the average smoker attempting to quit five times before permanent success. Moreover, the majority of smoking quit attempts result in relapse. Brain stimulation for smoke cessation is an exciting new area that builds on advancing neuroscience knowledge concerning the functional neurocircuitry of addiction. Cortical stimulation can now be performed non-invasively by transcranial magnetic stimulation (TMS). Several studies have shown that TMS can reduce cue-elicited craving in smokers. Previous research by group has shown that a single session of 15 minutes high frequency (10 Hz) repetitive TMS (rTMS) at 100% motor threshold over the left dorsal lateral prefrontal cortex (DLPFC) can reduce cue-induced craving compared to sham TMS. However, the mechanism by which craving is reduced by rTMS is poorly understood both at behavioral and neural levels. Neuroimaging studies in nicotine dependence have revealed cue-related responses in numerous brain areas, including frontal, parietal cortices and subcortical areas. Recently functional magnetic resonance imaging (fMRI) studies by the group have shown that cue-induced craving induced brain activation in ventral medial prefrontal cortex (VMPFC), including medial frontal, orbital frontal and anterior cingulate. This Chair Research Development Fund (CRDF) pilot proposal will integrate two new techniques- TMS and fMRI to investigate DLPFC-VMPFC pathway in smokers. Using double-masked methods investigators hypothesize that cue-induced exposure will induce brain activity in VMPFC, and 15 minutes rTMS over DLPFC will reduce cue-induced craving through modulating DLPFC-VMPFC pathway (increased activity DLPFC and decreased activity VMPFC).
Interventions
DEVICETranscranial Magnetic Stimulation
Sponsors
Xingbao Li
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
SINGLE (Subject)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Smoke 10 or more cigarettes per day and have a carbon monoxide (CO) level \> 10 ppm indicative of recent smoking. * Not received substance abuse treatment within the previous 30 days. * Meet criteria for nicotine dependence as determined by the FTND. * Be in stable mental and physical health. * If female, test non-pregnant and use adequate birth control. * No evidence of focal or diffuse brain lesion on MRI. * Be willing to provide informed consent. * Be able to comply with protocol requirements and likely to complete all study procedures.
Exclusion criteria
* Current dependence, defined by DSM-V criteria, on any psychoactive substances other than nicotine or caffeine. * Contraindication to MRI (e.g., presence of metal in the skull, orbits or intracranial cavity, claustrophobia). * Contraindication to rTMS (history of neurological disorder or seizure, increased intracranial pressure, brain surgery, or head trauma with loss of consciousness for \> 15 minutes, implanted electronic device, metal in the head, or pregnancy). * History of autoimmune, endocrine, viral, or vascular disorder affecting the brain. * History or MRI evidence of neurological disorder that would lead to local or diffuse brain lesions or significant physical impairment. * Unstable cardiac disease, uncontrolled hypertension, severe renal or liver insufficiency, or sleep apnea. * Life time history of major Axis I disorders such as: Bipolar Affective disorder (BPAD), Schizophrenia, Post-traumatic Stress disorder (PTSD) or Dementia or Major Depression. * Self report of \>21 standard alcohol drinks per week in any week in the 30 days prior to screening. * Other forms of nicotine delivery, such as nicotine patch, electronic cigarettes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Changes in fMRI Neural Activation Patterns | 7 days | During MRI scan in which participants will watch smoking picture, investigators will measure the change in neural activity in reward neural circuit. Whole brain imaging analysis and network analysis will be performed. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Reduction of Smoking Cue Craving | pre-TMS and post-TMS approx, 30 minutes. | visual analog scale for cue craving. Participants will be asked ' Right now, I would rate the amount of my craving to smoke as:'. The minimum score is 0, and the Maximum score is 7. There are 10 items. The total minimum score is 0, and the total maximum score is 70. A higher score is more craving to smoke a cigarette. The fewer values are considered to be a better outcome. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Sham rTMS The sham TMS system will be connected to an electrical generator on a 9 V battery and electrodes will be placed over the prefrontal cortex. The regulator is triggered by the TMS machine to allow brief, microsecond, pulses of the electrical current through to the skin on the subjects' forehead. Electrical stimulation will be triggered by the TMS machine to correspond to the sham TMS pulses.
Transcranial Magnetic Stimulation | 5 |
| Active rTMS Stimulation frequency for all active subjects: 10 Hertz - Pulse train duration (on time) 5 seconds, Inter-train interval (off time) 10 seconds (15 second cycle time), Power (intensity) level 100% rMT, Total 60 trains, 15 minutes, Total pulses 3000.
Transcranial Magnetic Stimulation | 6 |
| Total | 11 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Active rTMS | Sham rTMS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical Between 18 and 65 years | 6 Participants | 5 Participants | 11 Participants |
| Age, Continuous | 41.1 years STANDARD_DEVIATION 13.4 | 38.0 years STANDARD_DEVIATION 13.5 | 39.7 years STANDARD_DEVIATION 12.9 |
| Region of Enrollment United States | 6 participants | 5 participants | 11 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 3 Participants | 2 Participants | 5 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 5 | 0 / 6 |
| other Total, other adverse events | 0 / 5 | 1 / 6 |
| serious Total, serious adverse events | 0 / 5 | 0 / 6 |
Outcome results
Primary
Changes in fMRI Neural Activation Patterns
During MRI scan in which participants will watch smoking picture, investigators will measure the change in neural activity in reward neural circuit. Whole brain imaging analysis and network analysis will be performed.
Time frame: 7 days
Population: Effect of rTMS on Cue-induced Brain Activity: Left accumbens and Right medial orbital frontal cortex.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham rTMS | Changes in fMRI Neural Activation Patterns | Left accumbens | 0.14 % change | Standard Error 0.09 |
| Sham rTMS | Changes in fMRI Neural Activation Patterns | Right medial orbital frontal cortex | 0.13 % change | Standard Error 0.09 |
| Active rTMS | Changes in fMRI Neural Activation Patterns | Left accumbens | -0.38 % change | Standard Error 0.13 |
| Active rTMS | Changes in fMRI Neural Activation Patterns | Right medial orbital frontal cortex | -0.22 % change | Standard Error 0.1 |
Secondary
Reduction of Smoking Cue Craving
visual analog scale for cue craving. Participants will be asked ' Right now, I would rate the amount of my craving to smoke as:'. The minimum score is 0, and the Maximum score is 7. There are 10 items. The total minimum score is 0, and the total maximum score is 70. A higher score is more craving to smoke a cigarette. The fewer values are considered to be a better outcome.
Time frame: pre-TMS and post-TMS approx, 30 minutes.
Population: The primary behavioral measure of cue craving was taken to be the contrast (difference) between active and sham rTMS in the pre- to post-experiment change in subjective craving. A two-factor mixed model (treatment: active vs sham) and (time: pre- vs post) were performed on cigarette-craving ratings.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Sham rTMS | Reduction of Smoking Cue Craving | Pre-TMS | 5.3 units on a scale | Standard Deviation 2.4 |
| Sham rTMS | Reduction of Smoking Cue Craving | Post-TMS | 6.5 units on a scale | Standard Deviation 2.1 |
| Active rTMS | Reduction of Smoking Cue Craving | Pre-TMS | 6.8 units on a scale | Standard Deviation 2.3 |
| Active rTMS | Reduction of Smoking Cue Craving | Post-TMS | 6.4 units on a scale | Standard Deviation 2.4 |