Nicotine Dependence
Conditions
Keywords
TMS, nicotine dependence, smoking cessation
Brief summary
Cigarette smoking remains a significant public health concern. A magnetic field applied to the outside of the skull can produce electrical activity in the brain without significant pain or the need for anesthesia. Sessions of magnetic stimulation or superficial stimulation that does not reach the brain will be used to determine if magnetic stimulation can reduce cue-induced craving and cigarettes consumption in adult nicotine-dependent cigarette smokers. This project may lead to a new therapy for smoking cessation.
Detailed description
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). A few studies have shown that TMS can reduce cue-elicited craving in smokers. Previous research by our 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 (an area that is likely involved in inhibiting craving) can reduce cue-induced craving compared to sham TMS. However, methodological concerns surrounding these preliminary findings limit definitive conclusions about the effectiveness of TMS over a longer period of time. This R21 proposal will integrate more rigorous experimental conditions, a true double-blind methodology, MRI guided stimulation site and a longer-term follow-up assessment. Using rigorous double-masked methods and MRI guided stimulation site, we propose that using active rTMS or sham rTMS, to determine whether 10 sessions over a two week period consisting of 15 minute high frequency rTMS can reduce cue-induced craving and cigarette consumption for cigarette smokers. The project will also optimize rational rTMS parameters to make TMS to an efficacious treatment for nicotine dependence. In the two years of project, we plan to recruit 42 treatment-seeking nicotine-dependent cigarette smokers, both males and females of all ethnic and racial groups between the ages of 18 and 60 to participate in the study. The 42 participants will be randomly assigned to receive active prefrontal TMS or sham prefrontal TMS. The data from this R21 will provide the information needed for launching a definitive larger-scale investigation into potential clinical applications of TMS in smoke cessation. The results from this pilot will also likely supply substantial information about the utility of cortical stimulation for smoke cessation.
Interventions
DEVICETranscranial magnetic stimulation
Transcranial magnetic stimulation (TMS) is a noninvasive (and relatively painless) brain stimulation technology that can focally stimulate the brain of an awake individual. A localized pulsed magnetic field transmitted through a TMS coil is able to focally stimulate the cortex by depolarizing superficial neurons inducing electrical currents in the brain. If TMS pulses are delivered repetitively and rhythmically, the process is called repetitive TMS (rTMS).
Sponsors
Medical University of South Carolina
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
1. Be between the ages of 18 and 60 years old. 2. Smoke 10 or more cigarettes per day and have a carbon monoxide (CO) level \> 10 ppm indicative of recent smoking. 3. Not received substance abuse treatment within the previous 30 days. 4. Meet criteria for nicotine dependence as determined by the FTND. 5. Be in stable mental and physical health. 6. If female, test non-pregnant and use adequate birth control. 7. No evidence of focal or diffuse brain lesion on MRI. 8. Be willing to provide informed consent. 9. Be able to comply with protocol requirements and likely to complete all study procedures.
Exclusion criteria
1. Current dependence, defined by DSM-V criteria, on any psychoactive substances other than nicotine or caffeine. 2. Contraindication to MRI (e.g., presence of metal in the skull, orbits or intracranial cavity, claustrophobia). 3. 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). 4. History of autoimmune, endocrine, viral, or vascular disorder affecting the brain. 5. History or MRI evidence of neurological disorder that would lead to local or diffuse brain lesions or significant physical impairment. 6. Unstable cardiac disease, uncontrolled hypertension, severe renal or liver insufficiency, or sleep apnea. 7. 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. 8. Self report of \>21 standard alcohol drinks per week in any week in the 30 days prior to screening. 9. Other forms of nicotine delivery, such as nicotine patch, electronic cigarettes
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Nicotine Consumption: Number of Cigarettes Per Day | 2 weeks of treatment | Nicotine consumption: We use cigarette diary for participant to record number of cigarettes smoked per day. |
| Percentage of Change of Cigarettes Per Day | 2 weeks | percentage of change of cigarettes per day =100\* ( cigarettes smoked per day at baseline - cigarettes smoked per day at the end of treatment) / cigarettes smoked per day at baseline |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Average Nicotine Craving as Assessed by the Questionnaire of Smoking Urges-Brief | 2 weeks of treatment | The Brief Questionnaire of Smoking Urges (QSU-Brief) consists of 10 statements about the respondent's feelings and thoughts about his or her desire to smoke cigarettes as he or she is completing the questionnaire. A higher number represents a stronger smoking urges. A lower score represents a weaker smoking urges. The lowest score is 10. The highest score is 70. |
| The Number of Participants Quitting on the Target Quit Date | 2 weeks of treatment | Quitting smoking on the target quit date. |
Countries
United States
Participant flow
Recruitment details
Assessed for eligibility (n=327), Excluded 280, Not meeting inclusion criteria: 275, and declined to participate: 5, lost contact before screening visit: 5
Participants by arm
| Arm | Count |
|---|---|
| Active TMS Repetitive TMS pulse stimulation
Transcranial magnetic stimulation: Transcranial magnetic stimulation (TMS) is a noninvasive (and relatively painless) brain stimulation technology that can focally stimulate the brain of an awake individual. A localized pulsed magnetic field transmitted through a TMS coil is able to focally stimulate the cortex by depolarizing superficial neurons inducing electrical currents in the brain. If TMS pulses are delivered repetitively and rhythmically, the process is called repetitive TMS (rTMS). | 22 |
| Sham TMS 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: Transcranial magnetic stimulation (TMS) is a noninvasive (and relatively painless) brain stimulation technology that can focally stimulate the brain of an awake individual. A localized pulsed magnetic field transmitted through a TMS coil is able to focally stimulate the cortex by depolarizing superficial neurons inducing electrical currents in the brain. If TMS pulses are delivered repetitively and rhythmically, the process is called repetitive TMS (rTMS). | 20 |
| Total | 42 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 1 | 3 |
Baseline characteristics
| Characteristic | Active TMS | Sham TMS | Total |
|---|---|---|---|
| Age, Continuous | 40.64 years STANDARD_DEVIATION 10.36 | 43.75 years STANDARD_DEVIATION 10.36 | 42.12 years STANDARD_DEVIATION 10.78 |
| cigarettes per day | 18.2 cigarettes per day STANDARD_DEVIATION 4.8 | 20.9 cigarettes per day STANDARD_DEVIATION 10.2 | 19.5 cigarettes per day STANDARD_DEVIATION 7.8 |
| Race/Ethnicity, Customized Race African Americans | 3 Participants | 1 Participants | 4 Participants |
| Race/Ethnicity, Customized Race Caucasian | 19 Participants | 19 Participants | 38 Participants |
| Region of Enrollment United States | 22 Participants | 20 Participants | 42 Participants |
| Sex: Female, Male Female | 12 Participants | 11 Participants | 23 Participants |
| Sex: Female, Male Male | 10 Participants | 9 Participants | 19 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 21 | 0 / 17 |
| other Total, other adverse events | 14 / 21 | 8 / 17 |
| serious Total, serious adverse events | 0 / 21 | 0 / 17 |
Outcome results
Primary
Nicotine Consumption: Number of Cigarettes Per Day
Nicotine consumption: We use cigarette diary for participant to record number of cigarettes smoked per day.
Time frame: 2 weeks of treatment
Population: two groups t test for percentage changed cigarettes per day: mixed model.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active TMS | Nicotine Consumption: Number of Cigarettes Per Day | 11.60 the number of cigarette | Standard Deviation 6.93 |
| Sham TMS | Nicotine Consumption: Number of Cigarettes Per Day | 13.73 the number of cigarette | Standard Deviation 9.18 |
p-value: 0.05Mixed Models Analysis
Primary
Percentage of Change of Cigarettes Per Day
percentage of change of cigarettes per day =100\* ( cigarettes smoked per day at baseline - cigarettes smoked per day at the end of treatment) / cigarettes smoked per day at baseline
Time frame: 2 weeks
Population: We compared active group to sham group in the percentage of reduction in cigarettes smoked per day.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active TMS | Percentage of Change of Cigarettes Per Day | 62.93 % change | Standard Deviation 10.74 |
| Sham TMS | Percentage of Change of Cigarettes Per Day | 38.43 % change | Standard Deviation 10.63 |
p-value: 0.05t-test, 2 sided
Secondary
Average Nicotine Craving as Assessed by the Questionnaire of Smoking Urges-Brief
The Brief Questionnaire of Smoking Urges (QSU-Brief) consists of 10 statements about the respondent's feelings and thoughts about his or her desire to smoke cigarettes as he or she is completing the questionnaire. A higher number represents a stronger smoking urges. A lower score represents a weaker smoking urges. The lowest score is 10. The highest score is 70.
Time frame: 2 weeks of treatment
Population: Weekly ratings for mixed model repeated measures. We reported the group means which includes 5 points each group.
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Active TMS | Average Nicotine Craving as Assessed by the Questionnaire of Smoking Urges-Brief | 25.01 score on a scale | Standard Deviation 14.45 |
| Sham TMS | Average Nicotine Craving as Assessed by the Questionnaire of Smoking Urges-Brief | 29.93 score on a scale | Standard Deviation 13.12 |
p-value: 0.05Mixed Models Analysis
Secondary
The Number of Participants Quitting on the Target Quit Date
Quitting smoking on the target quit date.
Time frame: 2 weeks of treatment
Population: Quitting at target quit date.
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Active TMS | The Number of Participants Quitting on the Target Quit Date | 5 participants |
| Sham TMS | The Number of Participants Quitting on the Target Quit Date | 0 participants |
p-value: 0.05Chi-squared