Recruiting

TARGETOptimizing Brain Excitability in Depression

Sponsor:

Stanford University

Code:

NCT07242105

Conditions

Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

Interventions

Active Single-Pulse TMS

Sham Single-Pulse TMS

TARGET-optimized TMS

Non-optimized (Open-Loop) TMS

EEG Recording

Study Details

Brief summary:

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).

Conditions

Major Depressive Disorder

Study ID

NCT07242105

Start date

Oct 23, 2025

Status verified date

Feb, 2026

Completion date

Nov 30, 2029

Anticipated

Primary completion date

Aug 30, 2029

Anticipated

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

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

Study Design

Enrollment

145 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: 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.

experimental: 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.

experimental: 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.

experimental: 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.

Interventions

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.

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.

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.

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.

EEG Recording

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

Intracranial EEG (iEEG) Recording

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

Primary outcome measure

Changes in Anterior EL-TEP Amplitude after single-pulse TMS (spTMS) [ Time Frame: Baseline, end of spTMS (6 hours) ]
Changes in Posterior EL-TEP Amplitude after spTMS [ Time Frame: Baseline, end of spTMS (6 hours) ]
Changes in intracranial TMS-Evoked Potential (iTEP) Amplitude after TMS-iEEG [ Time Frame: Baseline, end of spTMS (20 minutes) ]

Central Contacts and Locations

Central contacts

Jade T Truong, BS

408-840-3313 kellerlab@stanford.edu

Locations

University of Iowa

Recruiting

Iowa City, California, United States, 52246

Contacts

Jade T Truong, BS

408-840-3313 kellerlab@stanford.edu

Stanford University

Recruiting

Stanford, California, United States, 94305

Contacts

Jade T Truong, BS

408-840-3313 kellerlab@stanford.edu

Principal Investigator:

Corey J Keller, MD, PhD

More Information

Sponsor

Stanford University

Last update posted

Feb 10, 2026

Last verified

Feb, 2026

Keywords

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Stanford University on 2026-02-10.