Trial Outcomes & Findings for Examining the Effects of Neural Stimulation on Inhibitory Control and Cigarette Smoking (NCT NCT03960138)

Last Updated: 2023-03-10

Results Overview

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.

Recruitment status

COMPLETED

Study phase

Target enrollment

63 participants

Primary outcome timeframe

1 hour

Results posted on

2023-03-10

Participant Flow

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.

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.

Participant milestones

Participant milestones
Measure	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.	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.
Second TBS STARTED	20	21
Second TBS COMPLETED	16	21
Second TBS NOT COMPLETED	4	0
First TBS STARTED	20	21
First TBS COMPLETED	16	21
First TBS NOT COMPLETED	4	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Examining the Effects of Neural Stimulation on Inhibitory Control and Cigarette Smoking

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: 1 hour

Outcome measures

Outcome measures
Measure	Intermittent Theta-burst Stimulation (iTBS) n=37 Participants 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. The total duration of the iTBS protocol is 190 seconds. Participants will receive stimulation over the r.IFG (A series of 3-pulse bursts at 50 Hz repeated every 200ms (5 Hz) per train, 2 seconds per train, 20 trains, 10 second intertrain interval, 600 total pulses; 80% Resting Motor Threshold) using a figure 8 coil.	Continuous Theta-burst Stimulation (cTBS) n=37 Participants 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. The total duration of the cTBS protocol is 40 seconds. Participants will receive stimulation over the r.IFG (A series of 3-pulse bursts at 50 Hz repeated every 200 ms (5 Hz), 600 total pulses; 80% Resting Motor Threshold) using a figure 8 coil.
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 1.560	3.778 Percentage of correct trials Standard Error 2.006

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Intermittent Theta-burst Stimulation (iTBS) n=32 Participants 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. The total duration of the iTBS protocol is 190 seconds. Participants will receive stimulation over the r.IFG (A series of 3-pulse bursts at 50 Hz repeated every 200ms (5 Hz) per train, 2 seconds per train, 20 trains, 10 second intertrain interval, 600 total pulses; 80% Resting Motor Threshold) using a figure 8 coil.	Continuous Theta-burst Stimulation (cTBS) n=32 Participants 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. The total duration of the cTBS protocol is 40 seconds. Participants will receive stimulation over the r.IFG (A series of 3-pulse bursts at 50 Hz repeated every 200 ms (5 Hz), 600 total pulses; 80% Resting Motor Threshold) using a figure 8 coil.
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	34.593 Score on a scale Standard Error 2.547

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Intermittent Theta-burst Stimulation (iTBS) n=32 Participants 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. The total duration of the iTBS protocol is 190 seconds. Participants will receive stimulation over the r.IFG (A series of 3-pulse bursts at 50 Hz repeated every 200ms (5 Hz) per train, 2 seconds per train, 20 trains, 10 second intertrain interval, 600 total pulses; 80% Resting Motor Threshold) using a figure 8 coil.	Continuous Theta-burst Stimulation (cTBS) n=32 Participants 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. The total duration of the cTBS protocol is 40 seconds. Participants will receive stimulation over the r.IFG (A series of 3-pulse bursts at 50 Hz repeated every 200 ms (5 Hz), 600 total pulses; 80% Resting Motor Threshold) using a figure 8 coil.
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	26.031 Score on a scale Standard Error 2.071

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Intermittent Theta-burst Stimulation (iTBS) n=32 Participants 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. The total duration of the iTBS protocol is 190 seconds. Participants will receive stimulation over the r.IFG (A series of 3-pulse bursts at 50 Hz repeated every 200ms (5 Hz) per train, 2 seconds per train, 20 trains, 10 second intertrain interval, 600 total pulses; 80% Resting Motor Threshold) using a figure 8 coil.	Continuous Theta-burst Stimulation (cTBS) n=32 Participants 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. The total duration of the cTBS protocol is 40 seconds. Participants will receive stimulation over the r.IFG (A series of 3-pulse bursts at 50 Hz repeated every 200 ms (5 Hz), 600 total pulses; 80% Resting Motor Threshold) using a figure 8 coil.
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	28.968 Score on a scale Standard Error 2.275

PRIMARY outcome

Timeframe: 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.

Outcome measures

Outcome measures
Measure	Intermittent Theta-burst Stimulation (iTBS) n=37 Participants 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. The total duration of the iTBS protocol is 190 seconds. Participants will receive stimulation over the r.IFG (A series of 3-pulse bursts at 50 Hz repeated every 200ms (5 Hz) per train, 2 seconds per train, 20 trains, 10 second intertrain interval, 600 total pulses; 80% Resting Motor Threshold) using a figure 8 coil.	Continuous Theta-burst Stimulation (cTBS) n=37 Participants 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. The total duration of the cTBS protocol is 40 seconds. Participants will receive stimulation over the r.IFG (A series of 3-pulse bursts at 50 Hz repeated every 200 ms (5 Hz), 600 total pulses; 80% Resting Motor Threshold) using a figure 8 coil.
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	.321 Mean change in rz score. Standard Error 2.136

Adverse Events

Intermittent Theta-burst Stimulation (iTBS)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Continuous Theta-burst Stimulation (cTBS)

Serious events: 0 serious events

Other events: 8 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Intermittent Theta-burst Stimulation (iTBS) n=41 participants at risk 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.The total duration of the iTBS protocol is 190 seconds. Participants will receive stimulation over the r.IFG (A series of 3-pulse bursts at 50 Hz repeated every 200ms (5 Hz) per train, 2 seconds per train, 20 trains, 10 second intertrain interval, 600 total pulses; 80% Resting Motor Threshold) using a figure 8 coil.	Continuous Theta-burst Stimulation (cTBS) n=37 participants at risk 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.The total duration of the cTBS protocol is 40 seconds. Participants will receive stimulation over the r.IFG (A series of 3-pulse bursts at 50 Hz repeated every 200 ms (5 Hz), 600 total pulses; 80% Resting Motor Threshold) using a figure 8 coil.
Nervous system disorders Headache	17.1% 7/41 • 48 hours post treatment for each condition - baseline, iTBS, cTBS	18.9% 7/37 • 48 hours post treatment for each condition - baseline, iTBS, cTBS
Skin and subcutaneous tissue disorders Scalp Pain	2.4% 1/41 • 48 hours post treatment for each condition - baseline, iTBS, cTBS	5.4% 2/37 • 48 hours post treatment for each condition - baseline, iTBS, cTBS
General disorders Arm/Hand Pain	0.00% 0/41 • 48 hours post treatment for each condition - baseline, iTBS, cTBS	5.4% 2/37 • 48 hours post treatment for each condition - baseline, iTBS, cTBS
Nervous system disorders Numbness	2.4% 1/41 • 48 hours post treatment for each condition - baseline, iTBS, cTBS	0.00% 0/37 • 48 hours post treatment for each condition - baseline, iTBS, cTBS
Nervous system disorders Weakness	4.9% 2/41 • 48 hours post treatment for each condition - baseline, iTBS, cTBS	5.4% 2/37 • 48 hours post treatment for each condition - baseline, iTBS, cTBS
Nervous system disorders Loss of Dexterity	2.4% 1/41 • 48 hours post treatment for each condition - baseline, iTBS, cTBS	2.7% 1/37 • 48 hours post treatment for each condition - baseline, iTBS, cTBS
Eye disorders Change in Vision	0.00% 0/41 • 48 hours post treatment for each condition - baseline, iTBS, cTBS	2.7% 1/37 • 48 hours post treatment for each condition - baseline, iTBS, cTBS
Ear and labyrinth disorders Change in Hearing	2.4% 1/41 • 48 hours post treatment for each condition - baseline, iTBS, cTBS	5.4% 2/37 • 48 hours post treatment for each condition - baseline, iTBS, cTBS
Ear and labyrinth disorders Tinnitis	2.4% 1/41 • 48 hours post treatment for each condition - baseline, iTBS, cTBS	2.7% 1/37 • 48 hours post treatment for each condition - baseline, iTBS, cTBS
Gastrointestinal disorders Nausea	0.00% 0/41 • 48 hours post treatment for each condition - baseline, iTBS, cTBS	2.7% 1/37 • 48 hours post treatment for each condition - baseline, iTBS, cTBS
Gastrointestinal disorders Vomiting	2.4% 1/41 • 48 hours post treatment for each condition - baseline, iTBS, cTBS	5.4% 2/37 • 48 hours post treatment for each condition - baseline, iTBS, cTBS
Gastrointestinal disorders Loss of Appetite	2.4% 1/41 • 48 hours post treatment for each condition - baseline, iTBS, cTBS	2.7% 1/37 • 48 hours post treatment for each condition - baseline, iTBS, cTBS
Skin and subcutaneous tissue disorders Rash	2.4% 1/41 • 48 hours post treatment for each condition - baseline, iTBS, cTBS	2.7% 1/37 • 48 hours post treatment for each condition - baseline, iTBS, cTBS

Additional Information

Dr. Brett Froeliger

University of Missouri

Phone: 5738824785

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Intermittent Theta-burst Stimulation (iTBS) First n=20 Participants 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.	Continuous Theta-burst Stimulation (cTBS) First n=21 Participants 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.	Total n=41 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	20 Participants n=5 Participants	21 Participants n=7 Participants	41 Participants n=5 Participants
Age, Categorical >=65 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Sex: Female, Male Female	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Sex: Female, Male Male	12 Participants n=5 Participants	11 Participants n=7 Participants	23 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	19 Participants n=5 Participants	21 Participants n=7 Participants	40 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	2 Participants n=5 Participants	4 Participants n=7 Participants	6 Participants n=5 Participants
Race (NIH/OMB) White	17 Participants n=5 Participants	17 Participants n=7 Participants	34 Participants n=5 Participants
Race (NIH/OMB) More than one race	1 Participants n=5 Participants	0 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	20 Participants n=5 Participants	21 Participants n=7 Participants	41 Participants n=5 Participants