EEG Synchronized TMS Trial for Depression

NCT03421808 | Completed Phase 2 Results DMC FDA Device

• 2 other identifiers: Pro00074695R21MH106775-01
• Study Type: interventional
• Target: 34
• Locations: 1 country
• Sites: 1

Brief Summary

Daily prefrontal TMS for depression, as developed by the PI, involves delivering TMS pulses to the prefrontal cortex and not assessing what the actual EEG phase is of the person's brain. In cardiology, in order to stimulate the heart effectively, one has to know the rhythm and phase of the heartbeat in order to perform cardioversion. The investigators wonder if it is important to time the brain stimulation with the phase of the person's brain. The brain has definite rhythms, and cycles through being excited or resting. A common EEG rhythm is alpha frequency. Theoretically, the effect of the TMS pulse might be diminished if it was delivered when the brain was temporarily cycling into an off state. In the r21 part of this grant, the investigators designed and constructed a combined TMS/EEG/fMRI system. With that equipment the investigators found that TMS pulses have different effects deeper in the brain as a function of the EEG alpha phase. Pulses delivered during a rising phase produce larger blood flow changes deeper in the brain than do pulses delivered during a falling phase. In the R33 phase of the grant the investigators now take that idea into a small clinical trial in depression to test if synchronized pulses have a larger clinical effect than do non-synchronized pulses.

Conditions

Depression

Keywords

TMS; transcranial magnetic stimulation; brain stimulation

Outcome Measures

Primary Outcomes (1)

• Remission Rate

  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.

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

Secondary Outcomes (2)

• Number of Participants With EEG Phase Synchronization Frequency Changes

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

• EEG-TMS-fMRI Bold Changes in Cingulate Cortex

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

Study Arms (2)

SYNC TMS

EXPERIMENTAL

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.

Device: Transcranial Magnetic Stimulation (TMS)

Non-Sync TMS

ACTIVE COMPARATOR

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.

Device: Transcranial Magnetic Stimulation (TMS)

Interventions

Transcranial Magnetic Stimulation (TMS) DEVICE

TMS

Non-Sync TMS; SYNC TMS

Eligibility Criteria

• Age: 21 Years - 70 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Diagnosis of unipolar major depressive disorder, in a current major depressive episode, without psychotic features
• Pretreatment Hamilton score ≥ 20
• Age between 21 and 70 years
• Fixed and stable antidepressant medications for 3 weeks prior and during the rTMS trial. Limit on benzodiazapenes to lorazepam (or equivalent) up to 3 mg every day
• Moderate level of resistance to antidepressant treatment in the current episode, defined as failure of 1-4 adequate medication trials or intolerance to at least 3 trials, and duration of current episode ≤ 3 years
• No history of schizophrenia, schizoaffective disorder, other \[non mood disorder\] psychosis, depression secondary to a medical condition, mental retardation, substance dependence or abuse within the past year (except nicotine), bipolar disorder, psychotic features in this or previous episodes, amnestic disorder, dementia or MMSE ≤24, delirium, obsessive compulsive disorder, post-traumatic stress disorder, panic disorder
• No current Vagus Nerve Stimulation
• No history of failing to respond to an adequate course of ECT in this or any episode, and no ECT within the past 3 months
• No contraindication to MRI
• No contraindication to rTMS (history of neurological disorder or seizure (except induced by ECT), increased intracranial pressure, brain surgery, or head trauma with loss of consciousness for \>15 minutes, implanted electronic device, metal in the head, or pregnancy)
• No history of autoimmune, endocrine, viral, or vascular disorder. No unstable cardiac disease, uncontrolled hypertension, or sleep apnea
• No active suicidal intent or plan, or history of attempt within the past 12 months
• Willing to provide informed consent

You may not qualify if:

• To ensure that baseline levels of depression severity are stable at the time of study enrollment, patients will be dropped if they show \> 30% improvement in the HRSD score from the time of initial intake (e.g., screening) to the baseline assessment.
• Patients must have a recordable alpha frequency.

Sponsors & Collaborators

• Medical University of South Carolina: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Medical University of South Carolina Brain Stimulation Division

Charleston, South Carolina, 29425, United States

Location

MeSH Terms

Conditions

Depression

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Behavioral Symptoms; Behavior

Intervention Hierarchy (Ancestors)

Magnetic Field Therapy; Therapeutics

Limitations and Caveats

Limitations are a small sample, using the intrinsic alpha frequency in each group, and the preferred synchronization was done before the trial and may have changed over time.

Results Point of Contact

• Title: Mark S. George, MD
• Organization: Medical University of South Carolina

georgem@musc.edu

18438765142

Study Officials

• Mark S George, MD

  Medical University of South Carolina

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: All subjects will get EEGS and TMS, but in one group the TMS pulses are synchronized to the EEG, and in the other not. There is no way for the subject or treater or anyone to detect who is in which arm.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: In a double blind, randomized (1:1) trial enrolling only at MUSC over three years in 60 treatment resistant depressed patients, we hypothesize that daily prefrontal rTMS over 4-6 weeks with the initial TMS pulse of each train synchronized to the subject's alpha phase (SYNC TMS), will result in improvement in depression, and that these improvements will be greater than the improvements seen using the same form of treatment but not with the initial pulse synchronized (NON-SYNC TMS).

Study Record Dates

• First Submitted: January 23, 2018
• First Posted: February 5, 2018
• Study Start: November 30, 2018
• Primary Completion: January 1, 2022
• Study Completion: January 15, 2024
• Last Updated: November 4, 2025
• Results First Posted: August 14, 2025

Record last verified: 2025-10

Locations

US (1)