Major Depressive DisorderTARGETNCT07242105
Optimizing Brain Excitability in Depression
A study testing Active Single-Pulse TMS, TARGET-optimized TMS and Non-optimized (Open-Loop) TMS in people with Major Depressive Disorder, run by Stanford University at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 to 65 yearsHealthy volunteers can take part
- Conditions the study is for
- Major Depressive Disorder
- What is being tested?
- Active Single-Pulse TMS, TARGET-optimized TMS and Non-optimized (Open-Loop) TMS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 145 participants
- Where
- 2 sitesUnited States
- Study dates
- 23 Oct 2025to 30 Nov 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 65 years
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Show all 11Show fewer
- 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
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
University of Iowa
Iowa City, California, 52246
Jade T Truong, BS, 408-840-3313, kellerlab@stanford.edu
Aaron D Boes, MD, PhD
- Recruiting
Stanford University
Stanford, California, 94305
Jade T Truong, BS, 408-840-3313, kellerlab@stanford.edu
Corey J Keller, MD, PhD
About this study
Official title: Optimized Methods for Measuring 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).
- Conditions
- Major Depressive Disorder
- Being tested
- Active Single-Pulse TMS, Sham Single-Pulse TMS, TARGET-optimized TMS, Non-optimized (Open-Loop) TMS, EEG Recording
- Keywords
- tms, eeg
- Medical subject headings
- Depressive Disorder, Major
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Active Single-Pulse TMSDevice
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 TMSDevice
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 TMSDevice
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) TMSDevice
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 RecordingOther
Participants undergo concurrent 64-channel TMS-compatible scalp EEG recording during stimulation to measure TMS-evoked neural responses.
Intracranial EEG (iEEG) RecordingOther
Neurosurgical participants undergo intracranial EEG recording using clinically implanted electrodes during TMS to measure local and downstream neural activity.
| Study group | Role | What they receive |
|---|---|---|
| Active TMS, Sham TMS with iEEG | Experimental | 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. Receives: Device: Active Single-Pulse TMS; Device: Sham Single-Pulse TMS; Other: Intracranial EEG (iEEG) Recording |
| Sham TMS, Active TMS with iEEG | Experimental | 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. Receives: Device: Active Single-Pulse TMS; Device: Sham Single-Pulse TMS; Other: Intracranial EEG (iEEG) Recording |
| Optimized TMS, Non-optimized TMS with EEG | Experimental | 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. Receives: Device: TARGET-optimized TMS; Device: Non-optimized (Open-Loop) TMS; Other: EEG Recording |
| Non-optimized TMS, Optimized TMS with EEG | Experimental | 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. Receives: Device: TARGET-optimized TMS; Device: Non-optimized (Open-Loop) TMS; Other: EEG Recording |
What is being measured
The primary outcome is the main question the study is designed to answer.
Changes in Anterior EL-TEP Amplitude after single-pulse TMS (spTMS)
Changes in Early Local TMS-Evoked Potentials (EL-TEP) following 6 hours of either active or sham spTMS between optimized and non-optimized stimulation conditions in the anterior dlPFC.
Measured: Baseline, end of spTMS (6 hours)
Changes in Posterior EL-TEP Amplitude after spTMS
Changes in Early Local TMS-Evoked Potentials (EL-TEP) following 6 hours of either active or sham spTMS between optimized and non-optimized stimulation conditions in the posterior dlPFC.
Measured: Baseline, end of spTMS (6 hours)
Changes in intracranial TMS-Evoked Potential (iTEP) Amplitude after TMS-iEEG
Changes in the interaction between gyral/sulcal targets and coil angles (45 vs 90 degrees) on local dlPFC iTEP amplitude.
Measured: Baseline, end of spTMS (20 minutes)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Nov 2025
- Study start23 Oct 2025
- Primary completion30 Aug 2029 (estimated)
- Study completion30 Nov 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Major Depressive DisorderStudies of the same condition, open and under way.
- More trials run by Stanford UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 145 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Stanford University
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Responsible party
- Principal investigator, Corey Keller, Stanford University
- Investigators
- Corey J Keller, MD, PhD, Principal investigator, Stanford University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07242105
- Sponsor's protocol ID
- 72673-1
- Other IDs
- 1R01MH139650
- Acronym
- TARGET
- Status last verified
- Feb 2026
- First submitted
- 11 Nov 2025
- Last updated
- 10 Feb 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Feb 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Optimized Methods for Measuring Brain Excitability in Depression
- ClinicalTrials.gov ID
- NCT07242105
- Acronym / sponsor ID
- TARGET / 72673-1
- Conditions
- Major Depressive Disorder
- Keywords
- tms, eeg
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 145 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 23 Oct 2025 (actual)
- Primary completion
- 30 Aug 2029 (estimated)
- Study completion
- 30 Nov 2029 (estimated)
- First posted
- 21 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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).
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| Active TMS, Sham TMS with iEEG | Experimental | Device: Active Single-Pulse TMS, Device: Sham Single-Pulse TMS, Other: Intracranial EEG (iEEG) RecordingNeurosurgical 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. |
| Sham TMS, Active TMS with iEEG | Experimental | Device: Active Single-Pulse TMS, Device: Sham Single-Pulse TMS, Other: Intracranial EEG (iEEG) RecordingNeurosurgical 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. |
| Optimized TMS, Non-optimized TMS with EEG | Experimental | Device: TARGET-optimized TMS, Device: Non-optimized (Open-Loop) TMS, Other: EEG RecordingParticipants 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. |
| Non-optimized TMS, Optimized TMS with EEG | Experimental | Device: TARGET-optimized TMS, Device: Non-optimized (Open-Loop) TMS, Other: EEG RecordingParticipants 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. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- 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
Key exclusion criteria (11 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Active Single-Pulse TMSSingle-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 | Active TMS, Sham TMS with iEEG, Sham TMS, Active TMS with iEEG |
| Sham Single-Pulse TMSSham 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 | Active TMS, Sham TMS with iEEG, Sham TMS, Active TMS with iEEG |
| TARGET-optimized TMSSingle-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 TMS, Optimized TMS with EEG, Optimized TMS, Non-optimized TMS with EEG |
| Non-optimized (Open-Loop) TMSSingle-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. | Device | Non-optimized TMS, Optimized TMS with EEG, Optimized TMS, Non-optimized TMS with EEG |
| EEG RecordingParticipants undergo concurrent 64-channel TMS-compatible scalp EEG recording during stimulation to measure TMS-evoked neural responses. | Other | Non-optimized TMS, Optimized TMS with EEG, Optimized TMS, Non-optimized TMS with EEG |
| Intracranial EEG (iEEG) RecordingNeurosurgical participants undergo intracranial EEG recording using clinically implanted electrodes during TMS to measure local and downstream neural activity. | Other | Active TMS, Sham TMS with iEEG, Sham TMS, Active TMS with iEEG |
Primary outcome
Changes in Anterior EL-TEP Amplitude after single-pulse TMS (spTMS)
Time frame: Baseline, end of spTMS (6 hours)
Changes in Early Local TMS-Evoked Potentials (EL-TEP) following 6 hours of either active or sham spTMS between optimized and non-optimized stimulation conditions in the anterior dlPFC.
Changes in Posterior EL-TEP Amplitude after spTMS
Time frame: Baseline, end of spTMS (6 hours)
Changes in Early Local TMS-Evoked Potentials (EL-TEP) following 6 hours of either active or sham spTMS between optimized and non-optimized stimulation conditions in the posterior dlPFC.
Changes in intracranial TMS-Evoked Potential (iTEP) Amplitude after TMS-iEEG
Time frame: Baseline, end of spTMS (20 minutes)
Changes in the interaction between gyral/sulcal targets and coil angles (45 vs 90 degrees) on local dlPFC iTEP amplitude.
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Feb 2026.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Corey J Keller, MD, PhD principal investigator
Stanford University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active Single-Pulse TMS, TARGET-optimized TMS and Non-optimized (Open-Loop) TMS in people with Major Depressive Disorder, run by Stanford University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 10 Feb 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Jade T Truong, BS (408-840-3313, kellerlab@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Changes in Anterior EL-TEP Amplitude after single-pulse TMS (spTMS) (time frame: Baseline, end of spTMS (6 hours)). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Feb 2026.