Recruiting
Optimizing Brain Excitability in Depression
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).
ClinicalTrials.gov IDNCT07242105
PhaseNA
Enrollment145
SponsorStanford University
Age18 Years
SexALL
Conditions studied
Major Depressive Disorder
About this study
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).
Interventions
- Device: 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.
- 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.
- 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.
- 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.
- Other: EEG Recording — Participants undergo concurrent 64-channel TMS-compatible scalp EEG recording during stimulation to measure TMS-evoked neural responses.
- Other: Intracranial EEG (iEEG) Recording — Neurosurgical participants undergo intracranial EEG recording using clinically implanted electrodes during TMS to measure local and downstream neural activity.
Primary outcomes
- Changes in Anterior EL-TEP Amplitude after single-pulse TMS (spTMS) (Baseline, end of spTMS (6 hours))
- Changes in Posterior EL-TEP Amplitude after spTMS (Baseline, end of spTMS (6 hours))
- Changes in intracranial TMS-Evoked Potential (iTEP) Amplitude after TMS-iEEG (Baseline, end of spTMS (20 minutes))
Eligibility information
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 locations
- University of Iowa, Iowa City, California 52246 United States
- Stanford University, Stanford, California 94305 United States
Before you participate: Varda Clinical is an independent discovery tool, not the study sponsor or a medical provider. Eligibility can only be determined by the official study team. Discuss potential risks and benefits with a qualified healthcare professional.
Source: ClinicalTrials.gov. Record last refreshed by Varda Clinical: 2026-09-27.