Trial Outcomes & Findings for EEG Synchronized TMS Trial for Depression (NCT NCT03421808)

Last Updated: 2025-11-04

Results Overview

Depression Remission, as defined by the Hamilton Rating Scale for Depression, 24 item, score less than 10. Range is 0 to 52. Higher scores mean more severe depression.

Recruitment status

COMPLETED

Study phase

PHASE2/PHASE3

Target enrollment

34 participants

Primary outcome timeframe

At the 4th week of treatment (or 6 weeks in those who continue to 6 weeks).

Results posted on

2025-11-04

Participant Flow

34 were consented but subjects had to have a prestudy TMS/fMRI scan. Only 28 patients made it to actual randomization, and only 24 patients completed the trial. Data are presented on those who actually were randomized and had SYNC TMS or UNSYNC TMS.

Participant milestones

Participant milestones
Measure	SYNC TMS Patients will receive daily left prefrontal transcranial magnetic stimulation (TMS), 120% MT, 3000 pulses/session, for 30 sessions. They will have EEG and the TMS will be delivered at their individual alpha frequency (IAF) (8-12 Hz) and the first TMS pulse in each train of 40 pulses will be synchronized with the EEG so that the TMS pulse fires during the rising phase of the alpha rhythm. Transcranial Magnetic Stimulation (TMS): TMS	Non-Sync TMS Patients will receive daily left prefrontal transcranial Magnetic stimulation (TMS), 120% MT, 3000 pulses/session, for 30 sessions. They will have EEG and the TMS will be delivered at their individual alpha frequency (IAF) (8-12 Hz) and the first TMS pulse in each train of 40 pulses will NOT be synchronized with the EEG so that the TMS pulse fires during the rising phase of the alpha rhythm. This is the way conventional TMS is delivered now and is FDA approved. Transcranial Magnetic Stimulation (TMS): TMS
Overall Study STARTED	15	13
Overall Study COMPLETED	12	12
Overall Study NOT COMPLETED	3	1

Reasons for withdrawal

Reasons for withdrawal
Measure	SYNC TMS Patients will receive daily left prefrontal transcranial magnetic stimulation (TMS), 120% MT, 3000 pulses/session, for 30 sessions. They will have EEG and the TMS will be delivered at their individual alpha frequency (IAF) (8-12 Hz) and the first TMS pulse in each train of 40 pulses will be synchronized with the EEG so that the TMS pulse fires during the rising phase of the alpha rhythm. Transcranial Magnetic Stimulation (TMS): TMS	Non-Sync TMS Patients will receive daily left prefrontal transcranial Magnetic stimulation (TMS), 120% MT, 3000 pulses/session, for 30 sessions. They will have EEG and the TMS will be delivered at their individual alpha frequency (IAF) (8-12 Hz) and the first TMS pulse in each train of 40 pulses will NOT be synchronized with the EEG so that the TMS pulse fires during the rising phase of the alpha rhythm. This is the way conventional TMS is delivered now and is FDA approved. Transcranial Magnetic Stimulation (TMS): TMS
Overall Study COVID related problems	2	0
Overall Study Withdrawal by Subject	1	0
Overall Study Protocol Violation	0	1

Baseline Characteristics

EEG Synchronized TMS Trial for Depression

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	SYNC TMS n=12 Participants Patients will receive daily left prefrontal transcranial magnetic stimulation (TMS), 120% MT, 3000 pulses/session, for 30 sessions. They will have EEG and the TMS will be delivered at their individual alpha frequency (IAF) (8-12 Hz) and the first TMS pulse in each train of 40 pulses will be synchronized with the EEG so that the TMS pulse fires during the rising phase of the alpha rhythm. Transcranial Magnetic Stimulation (TMS): TMS	Non-Sync TMS n=12 Participants Patients will receive daily left prefrontal transcranial Magnetic stimulation (TMS), 120% MT, 3000 pulses/session, for 30 sessions. They will have EEG and the TMS will be delivered at their individual alpha frequency (IAF) (8-12 Hz) and the first TMS pulse in each train of 40 pulses will NOT be synchronized with the EEG so that the TMS pulse fires during the rising phase of the alpha rhythm. This is the way conventional TMS is delivered now and is FDA approved. Transcranial Magnetic Stimulation (TMS): TMS	Total n=24 Participants Total of all reporting groups
Age, Continuous	42 years STANDARD_DEVIATION 12.1 • n=15 Participants	44 years STANDARD_DEVIATION 12.4 • n=161 Participants	43 years STANDARD_DEVIATION 12.3 • n=100 Participants
Sex: Female, Male Female	9 Participants n=15 Participants	8 Participants n=161 Participants	17 Participants n=100 Participants
Sex: Female, Male Male	3 Participants n=15 Participants	4 Participants n=161 Participants	7 Participants n=100 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	1 Participants n=15 Participants	2 Participants n=161 Participants	3 Participants n=100 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	11 Participants n=15 Participants	10 Participants n=161 Participants	21 Participants n=100 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=15 Participants	0 Participants n=161 Participants	0 Participants n=100 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=15 Participants	0 Participants n=161 Participants	0 Participants n=100 Participants
Race (NIH/OMB) Asian	0 Participants n=15 Participants	0 Participants n=161 Participants	0 Participants n=100 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=15 Participants	0 Participants n=161 Participants	0 Participants n=100 Participants
Race (NIH/OMB) Black or African American	2 Participants n=15 Participants	0 Participants n=161 Participants	2 Participants n=100 Participants
Race (NIH/OMB) White	10 Participants n=15 Participants	10 Participants n=161 Participants	20 Participants n=100 Participants
Race (NIH/OMB) More than one race	0 Participants n=15 Participants	0 Participants n=161 Participants	0 Participants n=100 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=15 Participants	2 Participants n=161 Participants	2 Participants n=100 Participants
Region of Enrollment United States	12 participants n=15 Participants	12 participants n=161 Participants	24 participants n=100 Participants
Depression illness duration (weeks)	91 weeks STANDARD_DEVIATION 79.3 • n=15 Participants	60 weeks STANDARD_DEVIATION 50.4 • n=161 Participants	87 weeks STANDARD_DEVIATION 60.1 • n=100 Participants

PRIMARY outcome

Timeframe: At the 4th week of treatment (or 6 weeks in those who continue to 6 weeks).

Depression Remission, as defined by the Hamilton Rating Scale for Depression, 24 item, score less than 10. Range is 0 to 52. Higher scores mean more severe depression.

Outcome measures

Outcome measures
Measure	SYNC TMS n=12 Participants Patients will receive daily left prefrontal transcranial magnetic stimulation (TMS), 120% MT, 3000 pulses/session, for 30 sessions. They will have EEG and the TMS will be delivered at their individual alpha frequency (IAF) (8-12 Hz) and the first TMS pulse in each train of 40 pulses will be synchronized with the EEG so that the TMS pulse fires during the rising phase of the alpha rhythm. Transcranial Magnetic Stimulation (TMS): TMS	Non-Sync TMS n=12 Participants Patients will receive daily left prefrontal transcranial Magnetic stimulation (TMS), 120% MT, 3000 pulses/session, for 30 sessions. They will have EEG and the TMS will be delivered at their individual alpha frequency (IAF) (8-12 Hz) and the first TMS pulse in each train of 40 pulses will NOT be synchronized with the EEG so that the TMS pulse fires during the rising phase of the alpha rhythm. This is the way conventional TMS is delivered now and is FDA approved. Transcranial Magnetic Stimulation (TMS): TMS
Remission Rate	2 Participants	3 Participants

SECONDARY outcome

Timeframe: assessed at each treatment session up to 6 weeks, week 6 reported

Population: We analyzed only completers as we needed the full 30 sessions of EEG for complete analysis. We measured the degree of phase entrainment, as measured by the inter-trial phase coherence (ITPC) across treatment sessions for SYNC and UNSYNC patients. We also measured the entrainment phase , defined as the corresponding phase in the circular space of post-stimulation ITPC value (i.e., the phase at which the first maximum ITPC after rTMS pulse train occurs).

EEG phase synchronization will be assessed by collecting real-time EEG, and then calculating whether the person's EEG frequency changed after the first few pulses in the train to where the EEG then matches the TMS pulses exactly and all TMS pulses are delivered at precisely the same time in the EEG cycle. We investigated the relationship between the maximum percentage phase angle (i.e., the histogram peak in the circular space of phases) and the HAMD changes across sessions. this maximum percentage was our first measure of the robustness of (defined as the corresponding phase of the post-stimulation ITPC value in circular space) across the 6 weeks of treatment.

Outcome measures

Outcome measures
Measure	SYNC TMS n=12 Participants Patients will receive daily left prefrontal transcranial magnetic stimulation (TMS), 120% MT, 3000 pulses/session, for 30 sessions. They will have EEG and the TMS will be delivered at their individual alpha frequency (IAF) (8-12 Hz) and the first TMS pulse in each train of 40 pulses will be synchronized with the EEG so that the TMS pulse fires during the rising phase of the alpha rhythm. Transcranial Magnetic Stimulation (TMS): TMS	Non-Sync TMS n=12 Participants Patients will receive daily left prefrontal transcranial Magnetic stimulation (TMS), 120% MT, 3000 pulses/session, for 30 sessions. They will have EEG and the TMS will be delivered at their individual alpha frequency (IAF) (8-12 Hz) and the first TMS pulse in each train of 40 pulses will NOT be synchronized with the EEG so that the TMS pulse fires during the rising phase of the alpha rhythm. This is the way conventional TMS is delivered now and is FDA approved. Transcranial Magnetic Stimulation (TMS): TMS
Number of Participants With EEG Phase Synchronization Frequency Changes	3 Participants	1 Participants

SECONDARY outcome

Timeframe: At the 4th week of treatment (or 6 weeks in those who continue to 6 weeks).

Population: No participants were included in the analysis population for this outcome due to incomplete imaging data and lack of funding to perform analysis. Imaging data will not be analyzed at any point in the future. Although imaging data were collected for some participants, the data were incomplete and insufficient for analysis due to technical limitations and lack of funding to complete post-processing. Therefore, no participants were included in the analysis population for this outcome.

EEG-TMS-fMRI Bold changes in cingulate cortex. We will measure the BOLD fMRI changes that are caused by a TMS pulse over the prefrontal cortex, and determine whether they increase more after 4 weeks of therapy.

Outcome measures

Outcome data not reported

Adverse Events

SYNC TMS

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Non-Sync TMS

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	SYNC TMS n=15 participants at risk Patients will receive daily left prefrontal transcranial magnetic stimulation (TMS), 120% MT, 3000 pulses/session, for 30 sessions. They will have EEG and the TMS will be delivered at their individual alpha frequency (IAF) (8-12 Hz) and the first TMS pulse in each train of 40 pulses will be synchronized with the EEG so that the TMS pulse fires during the rising phase of the alpha rhythm. Transcranial Magnetic Stimulation (TMS): TMS	Non-Sync TMS n=13 participants at risk Patients will receive daily left prefrontal transcranial Magnetic stimulation (TMS), 120% MT, 3000 pulses/session, for 30 sessions. They will have EEG and the TMS will be delivered at their individual alpha frequency (IAF) (8-12 Hz) and the first TMS pulse in each train of 40 pulses will NOT be synchronized with the EEG so that the TMS pulse fires during the rising phase of the alpha rhythm. This is the way conventional TMS is delivered now and is FDA approved. Transcranial Magnetic Stimulation (TMS): TMS
Nervous system disorders Headache	26.7% 4/15 • Number of events 19 • The full extent of the trial, June 2019 until February 2022. For each subject this covered the time of clinical participation and 6 month follow-up. More specifically, this was the time of clinical participation (up to 6 weeks) and 6 month follow-up, approximately 7.5 months,	30.8% 4/13 • Number of events 22 • The full extent of the trial, June 2019 until February 2022. For each subject this covered the time of clinical participation and 6 month follow-up. More specifically, this was the time of clinical participation (up to 6 weeks) and 6 month follow-up, approximately 7.5 months,

Additional Information

Mark S. George, MD

Medical University of South Carolina

Phone: 18438765142

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place