Optimizing Brain Excitability in Depression

NCT ID: NCT07242105

Last Updated: 2026-02-10

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

145 participants

Study Classification

INTERVENTIONAL

Study Start Date

2025-10-23

Study Completion Date

2029-11-30

Brief Summary

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The goal of this study is to improve depression treatment by establishing reliable prefrontal excitability markers through Targeting with Automated Real-time Guidance for Enhancing TEPs (TARGET).

Detailed Description

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Conditions

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Major Depressive Disorder

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

CROSSOVER

Primary Study Purpose

BASIC_SCIENCE

Blinding Strategy

TRIPLE

Participants Investigators Outcome Assessors

Study Groups

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Active TMS, Sham TMS with iEEG

Neurosurgical participants receive both active single-pulse Transcranial Magnetic Stimulation (TMS) and sham single-pulse TMS delivered to predefined dlPFC sites while undergoing intracranial EEG recording. The order of active and sham stimulation is randomized.

Group Type EXPERIMENTAL

Active Single-Pulse TMS

Intervention Type DEVICE

Single-pulse transcranial magnetic stimulation is delivered to the left dorsolateral prefrontal cortex using a MagVenture X100 stimulator and B65 A/P coil across predefined locations, coil angles, and stimulation intensities.

Sham Single-Pulse TMS

Intervention Type DEVICE

Sham single-pulse TMS is delivered using a flipped coil and concurrent scalp electrical stimulation to mimic auditory and somatosensory sensations without producing cortical stimulation.

Intracranial EEG (iEEG) Recording

Intervention Type OTHER

Neurosurgical participants undergo intracranial EEG recording using clinically implanted electrodes during TMS to measure local and downstream neural activity.

Sham TMS, Active TMS with iEEG

Neurosurgical participants receive sham single-pulse TMS followed by active single-pulse TMS at predefined dlPFC sites during intracranial EEG recording. The order of stimulation conditions is randomized.

Group Type EXPERIMENTAL

Active Single-Pulse TMS

Intervention Type DEVICE

Single-pulse transcranial magnetic stimulation is delivered to the left dorsolateral prefrontal cortex using a MagVenture X100 stimulator and B65 A/P coil across predefined locations, coil angles, and stimulation intensities.

Sham Single-Pulse TMS

Intervention Type DEVICE

Sham single-pulse TMS is delivered using a flipped coil and concurrent scalp electrical stimulation to mimic auditory and somatosensory sensations without producing cortical stimulation.

Intracranial EEG (iEEG) Recording

Intervention Type OTHER

Neurosurgical participants undergo intracranial EEG recording using clinically implanted electrodes during TMS to measure local and downstream neural activity.

Optimized TMS, Non-optimized TMS with EEG

Participants receive both TARGET optimized single-pulse TMS and non-optimized (open-loop) single-pulse TMS to the dlPFC while undergoing concurrent scalp EEG. The sequence of optimized and non-optimized stimulation is randomized.

Group Type EXPERIMENTAL

TARGET-optimized TMS

Intervention Type DEVICE

Single-pulse TMS parameters (location, angle, and intensity) are adjusted in real time using the TARGET closed-loop algorithm based on concurrent EEG measurements to deliver optimized stimulation.

Non-optimized (Open-Loop) TMS

Intervention Type DEVICE

Single-pulse TMS is delivered using a predefined open-loop set of stimulation parameter combinations across multiple dlPFC locations, coil angles, and intensities without real-time adjustment.

EEG Recording

Intervention Type OTHER

Participants undergo concurrent 64-channel TMS-compatible scalp EEG recording during stimulation to measure TMS-evoked neural responses.

Non-optimized TMS, Optimized TMS with EEG

Participants receive non-optimized (open-loop) single-pulse TMS followed by TARGET optimized single-pulse TMS to the dlPFC with concurrent scalp EEG. The order of stimulation conditions is randomized.

Group Type EXPERIMENTAL

TARGET-optimized TMS

Intervention Type DEVICE

Single-pulse TMS parameters (location, angle, and intensity) are adjusted in real time using the TARGET closed-loop algorithm based on concurrent EEG measurements to deliver optimized stimulation.

Non-optimized (Open-Loop) TMS

Intervention Type DEVICE

Single-pulse TMS is delivered using a predefined open-loop set of stimulation parameter combinations across multiple dlPFC locations, coil angles, and intensities without real-time adjustment.

EEG Recording

Intervention Type OTHER

Participants undergo concurrent 64-channel TMS-compatible scalp EEG recording during stimulation to measure TMS-evoked neural responses.

Interventions

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Active Single-Pulse TMS

Single-pulse transcranial magnetic stimulation is delivered to the left dorsolateral prefrontal cortex using a MagVenture X100 stimulator and B65 A/P coil across predefined locations, coil angles, and stimulation intensities.

Intervention Type DEVICE

Sham Single-Pulse TMS

Sham single-pulse TMS is delivered using a flipped coil and concurrent scalp electrical stimulation to mimic auditory and somatosensory sensations without producing cortical stimulation.

Intervention Type DEVICE

TARGET-optimized TMS

Single-pulse TMS parameters (location, angle, and intensity) are adjusted in real time using the TARGET closed-loop algorithm based on concurrent EEG measurements to deliver optimized stimulation.

Intervention Type DEVICE

Non-optimized (Open-Loop) TMS

Single-pulse TMS is delivered using a predefined open-loop set of stimulation parameter combinations across multiple dlPFC locations, coil angles, and intensities without real-time adjustment.

Intervention Type DEVICE

EEG Recording

Participants undergo concurrent 64-channel TMS-compatible scalp EEG recording during stimulation to measure TMS-evoked neural responses.

Intervention Type OTHER

Intracranial EEG (iEEG) Recording

Neurosurgical participants undergo intracranial EEG recording using clinically implanted electrodes during TMS to measure local and downstream neural activity.

Intervention Type OTHER

Eligibility Criteria

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Inclusion Criteria

* Men and women, ages 18 to 65
* Diagnosis of major depressive disorder, assessed through a Structured Clinical Interview for DSM-5 (SCID-5)
* In a current depressive episode, assessed through a Structured Clinical Interview for Diagnostic and Statistical Manual of Mental Disorders (DSM-5) (SCID-5)
* Moderate-to-severe depression as indicated by a score between 11-20 on the Quick Inventory of Depressive Symptoms (QIDS)
* Must comprehend English well to ensure adequate comprehension of the EEG and TMS instructions, and of clinical scales
* No current or history of neurological disorders
* No seizure disorder or risk of seizures
* Neurosurgical patients: Men and women ages 18-65 with medication-refractory epilepsy who are admitted for phase II intracranial monitoring to detect a seizure focus will be considered appropriate for this study. Participants must have the intellectual capacity to understand the consent process and agree to the study.

Exclusion Criteria

* Those with a contraindication for MRIs (e.g. implanted metal)
* History of head trauma with loss of consciousness
* History of seizures or on medications that reduce seizure threshold (e.g., olanzapine, chlorpromazine, lithium)
* Neurological or uncontrolled medical disease
* Any unstable medical condition
* Active substance abuse
* Diagnosis of psychotic or bipolar disorder
* A prior history of Electroconvulsive Therapy (ECT) failure
* History of suicide attempt in the past year
* Currently pregnant or breastfeeding
* Repetitive Transcranial Magnetic Stimulation (rTMS) treatment in the past six months
Minimum Eligible Age

18 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Institute of Mental Health (NIMH)

NIH

Sponsor Role collaborator

Stanford University

OTHER

Sponsor Role lead

Responsible Party

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Corey Keller

Associate Professor

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Corey J Keller, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

Stanford University

Locations

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University of Iowa

Iowa City, California, United States

Site Status RECRUITING

Stanford University

Stanford, California, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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Jade T Truong, BS

Role: CONTACT

408-840-3313

Facility Contacts

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Jade T Truong, BS

Role: primary

408-840-3313

Jade T Truong, BS

Role: primary

408-840-3313

Other Identifiers

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1R01MH139650

Identifier Type: NIH

Identifier Source: secondary_id

View Link

72673-1

Identifier Type: -

Identifier Source: org_study_id

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