Tobacco Use Disorder
Conditions
Brief summary
The purpose of this research study is to examine the effects of theta-burst Transcranial Magnetic Stimulation on inhibitory control and smoking among adult cigarette smokers.
Interventions
Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected. Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected.
Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected. Continuous TBS (cTBS) which is thought to temporarily dampen brain activity in that specific area.
Sponsors
University of Missouri-Columbia
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
DOUBLE (Subject, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 65 Years
Healthy volunteers
Yes
Inclusion criteria
1. Be between the ages of 18 and 65. 2. Be in stable mental and physical health. 3. Be willing to provide informed consent. 4. Be able to comply with protocol requirements and likely to complete all study procedures. 5. Be a current nicotine dependent cigarette smoker (smoke ≥10 cigs/day) with a minimum smoking history of smoking an average of ≥ 10 cigs/day over the past two years.
Exclusion criteria
* 1\. Contraindication to MRI (e.g., presence of metal in the skull, orbits or intracranial cavity, claustrophobia). 2\. Contraindication to TMS (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, as indicated by a positive urine pregnancy test at screening). 3\. Any use of substances that lower seizure threshold (such as thyroid medications or cocaine). 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\. BAC greater than 0.0. 8. Any other condition or concern that in the Investigator's opinion would impact participant safety, compliance with study instructions, or potentially confound the interpretation of the study results.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Change in Behavioral Inhibition Between Baseline and 1 Hour Post Treatment. | 1 hour | Changes in errors of omission on an inhibitory control task performed prior to and immediately after cTBS, and changes in errors of omission on an inhibitory control task performed prior to and immediately after iTBS. Outcomes will be measured as the mean change in behavioral performance percent correct on inhibition trials between baseline and 1 hour post treatment. Scores on the inhibitory control task range from 0% correct to 100% correct, and the change from pre-post TBS is expressed as a percent increase or decrease in performance. Positive values represent an improved outcome, whereas negative values represent a worse outcome. |
| The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Craving to Smoke 1 Hour Post Treatment. | 1 hour | Changes in self-reported craving to smoke will be assessed using the Questionnaire on Smoking Urges brief (QSUb) at 1 hour post session on each of three conditions (Baseline, cTBS, iTBS). The values are calculated as the mean of the scores between conditions at 1 hour post session. Scores on the QSUb range from 10 to 70. The lower the score, the better the outcome. |
| The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Craving to Smoke 24hrs Post Treatment Between Conditions. | 24 hours | Changes in self-reported craving to smoke will be assessed using the Questionnaire on Smoking Urges brief (QSUb) at 24hrs post session on each of three conditions (Baseline, cTBS, iTBS). The values are calculated as the mean of the scores between conditions at 24 hours post session. Scores on the QSUb range from 10 to 70. The lower the score, the better the outcome. |
| The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Craving to Smoke 48hrs Post Treatment Between Conditions. | 48 hours | Changes in self-reported craving to smoke will be assessed using the Questionnaire on Smoking Urges brief (QSUb) at 48hrs post session on each of three conditions (Baseline, cTBS, iTBS). The values are calculated as the mean of the scores between conditions at 48 hours post session. Scores on the QSUb range from 10 to 70. The lower the score, the better the outcome. |
| The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Hyperdirect Brain Circuit Function Between Pre and Post Session. | 1 hour | Changes in inhibitory control task functional connectivity between the r.IFG and nodes within the hyperdirect pathway (r.SMA, r.STN) prior to and immediately after cTBS, and changes in inhibitory control task functional connectivity between the r.IFG and nodes within the hyperdirect pathway (r.SMA, r.STN) prior to and immediately after iTBS. Outcomes will be measured as the transformed correlation (rZ value) of BOLD functional connectivity collected during the inhibitory task. The higher the rZ, the better the outcome. |
Countries
United States
Participant flow
Recruitment details
63 participants were consented and screened. 19 were excluded, 7 due to screen failure, 6 due to lost to follow up, 5 were participant initiated withdrawal and 1 due to investigator initiated withdrawal.
Pre-assignment details
Of the 44 participants, 3 were excluded - 2 due to lost to follow up and 1 due to investigator initiated withdrawal. A total of 41 participants were randomized and started treatment.
Participants by arm
| Arm | Count |
|---|---|
| Intermittent Theta-burst Stimulation (iTBS) First Cross-over design - participants will receive both experimental treatments. Intermittent Theta-burst stimulation (iTBS): Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected. Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected.
Continuous Theta-burst stimulation (cTBS): Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected. Continuous TBS (cTBS) which is thought to temporarily dampen brain activity in that specific area. | 20 |
| Continuous Theta-burst Stimulation (cTBS) First Cross-over design - participants will receive both experimental treatments. Continuous Theta-burst stimulation (cTBS): Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected. Continuous TBS (cTBS) which is thought to temporarily dampen brain activity in that specific area.
Intermittent Theta-burst stimulation (iTBS): Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected. Theta-burst stimulation (TBS), a form of repetitive transcranial magnetic stimulation (rTMS), affects brain areas stimulated directly underneath the scalp and brain areas that are functionally connected. | 21 |
| Total | 41 |
Baseline characteristics
| Characteristic | Intermittent Theta-burst Stimulation (iTBS) First | Continuous Theta-burst Stimulation (cTBS) First | 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 | 20 Participants | 21 Participants | 41 Participants |
| Ethnicity (NIH/OMB) Hispanic or Latino | 1 Participants | 0 Participants | 1 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 19 Participants | 21 Participants | 40 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 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 | 2 Participants | 4 Participants | 6 Participants |
| Race (NIH/OMB) More than one race | 1 Participants | 0 Participants | 1 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 | 17 Participants | 17 Participants | 34 Participants |
| Region of Enrollment United States | 20 Participants | 21 Participants | 41 Participants |
| Sex: Female, Male Female | 8 Participants | 10 Participants | 18 Participants |
| Sex: Female, Male Male | 12 Participants | 11 Participants | 23 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 41 | 0 / 37 |
| other Total, other adverse events | 8 / 41 | 8 / 37 |
| serious Total, serious adverse events | 0 / 41 | 0 / 37 |
Outcome results
Primary
The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Change in Behavioral Inhibition Between Baseline and 1 Hour Post Treatment.
Changes in errors of omission on an inhibitory control task performed prior to and immediately after cTBS, and changes in errors of omission on an inhibitory control task performed prior to and immediately after iTBS. Outcomes will be measured as the mean change in behavioral performance percent correct on inhibition trials between baseline and 1 hour post treatment. Scores on the inhibitory control task range from 0% correct to 100% correct, and the change from pre-post TBS is expressed as a percent increase or decrease in performance. Positive values represent an improved outcome, whereas negative values represent a worse outcome.
Time frame: 1 hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intermittent Theta-burst Stimulation (iTBS) | The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Change in Behavioral Inhibition Between Baseline and 1 Hour Post Treatment. | -3.078 Percentage of correct trials | Standard Error 1.56 |
| Continuous Theta-burst Stimulation (cTBS) | The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Change in Behavioral Inhibition Between Baseline and 1 Hour Post Treatment. | 3.778 Percentage of correct trials | Standard Error 2.006 |
Primary
The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Craving to Smoke 1 Hour Post Treatment.
Changes in self-reported craving to smoke will be assessed using the Questionnaire on Smoking Urges brief (QSUb) at 1 hour post session on each of three conditions (Baseline, cTBS, iTBS). The values are calculated as the mean of the scores between conditions at 1 hour post session. Scores on the QSUb range from 10 to 70. The lower the score, the better the outcome.
Time frame: 1 hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intermittent Theta-burst Stimulation (iTBS) | The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Craving to Smoke 1 Hour Post Treatment. | 37.281 Score on a scale | Standard Error 2.191 |
| Continuous Theta-burst Stimulation (cTBS) | The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Craving to Smoke 1 Hour Post Treatment. | 34.593 Score on a scale | Standard Error 2.547 |
Primary
The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Craving to Smoke 24hrs Post Treatment Between Conditions.
Changes in self-reported craving to smoke will be assessed using the Questionnaire on Smoking Urges brief (QSUb) at 24hrs post session on each of three conditions (Baseline, cTBS, iTBS). The values are calculated as the mean of the scores between conditions at 24 hours post session. Scores on the QSUb range from 10 to 70. The lower the score, the better the outcome.
Time frame: 24 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intermittent Theta-burst Stimulation (iTBS) | The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Craving to Smoke 24hrs Post Treatment Between Conditions. | 28.656 Score on a scale | Standard Error 2.581 |
| Continuous Theta-burst Stimulation (cTBS) | The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Craving to Smoke 24hrs Post Treatment Between Conditions. | 26.031 Score on a scale | Standard Error 2.071 |
Primary
The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Craving to Smoke 48hrs Post Treatment Between Conditions.
Changes in self-reported craving to smoke will be assessed using the Questionnaire on Smoking Urges brief (QSUb) at 48hrs post session on each of three conditions (Baseline, cTBS, iTBS). The values are calculated as the mean of the scores between conditions at 48 hours post session. Scores on the QSUb range from 10 to 70. The lower the score, the better the outcome.
Time frame: 48 hours
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intermittent Theta-burst Stimulation (iTBS) | The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Craving to Smoke 48hrs Post Treatment Between Conditions. | 29.781 Score on a scale | Standard Error 2.613 |
| Continuous Theta-burst Stimulation (cTBS) | The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Craving to Smoke 48hrs Post Treatment Between Conditions. | 28.968 Score on a scale | Standard Error 2.275 |
Primary
The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Hyperdirect Brain Circuit Function Between Pre and Post Session.
Changes in inhibitory control task functional connectivity between the r.IFG and nodes within the hyperdirect pathway (r.SMA, r.STN) prior to and immediately after cTBS, and changes in inhibitory control task functional connectivity between the r.IFG and nodes within the hyperdirect pathway (r.SMA, r.STN) prior to and immediately after iTBS. Outcomes will be measured as the transformed correlation (rZ value) of BOLD functional connectivity collected during the inhibitory task. The higher the rZ, the better the outcome.
Time frame: 1 hour
| Arm | Measure | Value (MEAN) | Dispersion |
|---|---|---|---|
| Intermittent Theta-burst Stimulation (iTBS) | The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Hyperdirect Brain Circuit Function Between Pre and Post Session. | -3.078 Mean change in rz score. | Standard Error 1.56 |
| Continuous Theta-burst Stimulation (cTBS) | The Effects of cTBS vs. iTBS TMS Applied to the r.IFG on Changes in Hyperdirect Brain Circuit Function Between Pre and Post Session. | .321 Mean change in rz score. | Standard Error 2.136 |