Major Depressive DisorderNCT07528157
Early Brainwave Biomarkers for Personalized Neuromodulation in Treatment-resistant Depression
A study testing Personalized iTBS and Non-Personalized iTBS in people with Major Depressive Disorder and Treatment Resistant Depression, run by Stanford University at 1 site in United States.
Trial summary
This study tests whether a brain stimulation treatment for depression called intermittent theta burst stimulation (iTBS) can be improved by tailoring it to each individual. A type of brain signal measured with electroencephalography (EEG) after a single pulse of brain stimulation, called an early local TMS-evoked… Read more about this study
- Who is it for?
- Ages 18 to 65 years
- Conditions the study is for
- Major Depressive Disorder, Treatment Resistant Depression
- What is being tested?
- Personalized iTBS and Non-Personalized iTBS
- Type of treatment
- Medical device
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Jun 2026to 31 Dec 2027
- 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
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Aged 18-65 years
- Clinical diagnosis of Major Depressive Disorder (MDD), confirmed by structured clinical interview
- Current moderate-to-severe depressive episode (MADRS score ≥ 20)
- Moderate-to-severe treatment resistance, assessed using the Maudsley Staging Method
- Able to comprehend English sufficiently to complete study procedures and assessments
- Able to maintain stable antidepressant regimen or remain medication-free for at least 4 weeks prior to and during the study
Who cannot join
- Primary psychiatric diagnosis other than MDD
- Contraindications to MRI (e.g., implanted metal)
- Conditions or medications that may increase risk associated with TMS
- Prior exposure to repetitive TMS (rTMS)
- Non-response to electroconvulsive therapy (ECT)
- History of psychosurgery for depression
- High suicidal risk as assessed by the Columbia Suicide Severity Rating Scale (C-SSRS)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Early TMS-EEG Potentials as Biomarkers for Personalized Neuromodulation in Treatment-Resistant Depression (R61 Phase)
This study tests whether a brain stimulation treatment for depression called intermittent theta burst stimulation (iTBS) can be improved by tailoring it to each individual. A type of brain signal measured with electroencephalography (EEG) after a single pulse of brain stimulation, called an early local TMS-evoked potential (EL-TEP), is used to identify which stimulation settings work best for each participant. The investigators will compare individualized (personalized) iTBS settings to standard (non-personalized) settings and to inactive (sham) stimulation. Participants are adults with treatment-resistant depression.
- Being tested
- Personalized iTBS, Non-Personalized iTBS, Sham iTBS
- Keywords
- tms, eeg
- Medical subject headings
- Depressive Disorder, Major, Depressive Disorder, Treatment-Resistant
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Personalized iTBSDevice
Intermittent theta burst stimulation delivered to the left dorsolateral prefrontal cortex using individualized pulse count (600, 1200, or 1800 pulses) and intensity (90% or 120% rMT) determined by EL-TEP screening.
Non-Personalized iTBSDevice
Intermittent theta burst stimulation delivered to the left dorsolateral prefrontal cortex at fixed parameters: 1800 pulses, 120% resting motor threshold.
Sham iTBSDevice
Inactive sham stimulation using a shielded coil with electrical scalp stimulation to mimic sensory experience of active iTBS.
| Study group | Role | What they receive |
|---|---|---|
| Personalized iTBS | Experimental | Participants receive 10 sessions of iTBS using individually selected pulse count and intensity parameters identified during a prior screening phase as producing the greatest suppression of the EL-TEP biomarker. Receives: Device: Personalized iTBS |
| Non-Personalized iTBS | Active comparator | Participants receive 10 sessions of iTBS using standard fixed parameters (1800 pulses, 120% resting motor threshold). Receives: Device: Non-Personalized iTBS |
| Sham iTBS | Sham comparator | Participants receive 10 sessions of sham iTBS, matched in timing and scalp sensation to active stimulation using a shielded coil and scalp electrodes. Receives: Device: Sham iTBS |
What is being measured
The primary outcome is the main question the study is designed to answer.
Percent Change in Early Local TMS-Evoked Potential (EL-TEP) Amplitude
EL-TEP amplitude is the peak-to-trough amplitude of the early (20-60 ms) EEG response recorded over the left dorsolateral prefrontal cortex following single TMS pulses. Percent change is calculated from pre-iTBS to post-iTBS for each stimulation condition.
Measured: Baseline, end of 10 iTBS sessions within a single testing day (10 hours)
Secondary outcomes (8)
Acute EL-TEP Suppression Following Each Screened iTBS Condition
Percent change in EL-TEP amplitude from before to after each of the six screened iTBS parameter combinations during the screening phase.
Measured: Baseline, end of each iTBS session during the screening phase (3 screening days, up to approximately 3 weeks)
Trajectory of EL-TEP Change Across Multiple Sessions Within a Testing Day
EL-TEP amplitude measured before and after sessions 1, 2, 3, and 10 on each testing day to characterize cumulative effects.
Measured: Baseline, before and after sessions 1, 2, 3, and 10 within a single testing day (10 hours)
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Score
Clinician-administered scale assessing depressive symptom severity. Score range: 0-60 (higher scores indicate greater severity).
Measured: Baseline, end of each testing day (up to approximately 7 weeks)
Change in Quick Inventory of Depressive Symptomatology (QIDS) Score
Self-report measure of depressive symptom severity. Score range: 0-27 (higher scores indicate greater severity).
Measured: Baseline, end of each testing day (up to approximately 7 weeks)
Change in Generalized Anxiety Disorder 7-Item Scale (GAD-7) Score
Self-report measure of anxiety symptom severity. Score range: 0-21 (higher scores indicate greater severity).
Measured: Baseline, end of each testing day (up to approximately 7 weeks)
Change in N-Back Task Performance
Working memory performance assessed using the N-back task. Outcome is accuracy and reaction time.
Measured: Baseline, end of each testing day (up to approximately 7 weeks)
Change in Multi-Source Interference Task (MSIT) Performance
Executive function assessed using the MSIT. Outcome is accuracy and reaction time.
Measured: Baseline, end of each testing day (up to approximately 7 weeks)
Change in Affective Processing Task Performance
Emotional face recognition task performance. Outcome is accuracy.
Measured: Baseline, end of each testing day (up to approximately 7 weeks)
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2026
- Study start1 Jun 2026 (estimated)
- Primary completion31 Dec 2027 (estimated)
- Study completion31 Dec 2027 (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
- Model description
- All participants receive all three arms.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Outcomes assessor
- Enrolment
- 80 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
- NCT07528157
- Sponsor's protocol ID
- 85003-1
- Other IDs
- R61MH140799
- Status last verified
- Apr 2026
- First submitted
- 7 Apr 2026
- Last updated
- 14 Apr 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 14 Apr 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Early TMS-EEG Potentials as Biomarkers for Personalized Neuromodulation in Treatment-Resistant Depression (R61 Phase)
- ClinicalTrials.gov ID
- NCT07528157
- Acronym / sponsor ID
- 85003-1
- Keywords
- tms, eeg
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 80 participants (estimated)
- Lead sponsor
- Stanford UniversityUniversity, hospital or other
- Collaborators
- National Institute of Mental Health (NIMH)
- Study start
- 1 Jun 2026 (estimated)
- Primary completion
- 31 Dec 2027 (estimated)
- Study completion
- 31 Dec 2027 (estimated)
- First posted
- 14 Apr 2026 (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.
This study tests whether a brain stimulation treatment for depression called intermittent theta burst stimulation (iTBS) can be improved by tailoring it to each individual. A type of brain signal measured with electroencephalography (EEG) after a single pulse of brain stimulation, called an early local TMS-evoked potential (EL-TEP), is used to identify which stimulation settings work best for each participant. The investigators will compare individualized (personalized) iTBS settings to standard (non-personalized) settings and to inactive (sham) stimulation. Participants are adults with treatment-resistant depression.
Study design
- Primary purpose
- Basic science
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, outcomes assessor)
- Number of arms
- 3
- Model description
- All participants receive all three arms.
| Arm | Type | Receives |
|---|---|---|
| Personalized iTBS | Experimental | Device: Personalized iTBSParticipants receive 10 sessions of iTBS using individually selected pulse count and intensity parameters identified during a prior screening phase as producing the greatest suppression of the EL-TEP biomarker. |
| Non-Personalized iTBS | Active comparator | Device: Non-Personalized iTBSParticipants receive 10 sessions of iTBS using standard fixed parameters (1800 pulses, 120% resting motor threshold). |
| Sham iTBS | Sham comparator | Device: Sham iTBSParticipants receive 10 sessions of sham iTBS, matched in timing and scalp sensation to active stimulation using a shielded coil and scalp electrodes. |
Who may qualify
- Ages
- 18 to 65 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Aged 18-65 years
- Clinical diagnosis of Major Depressive Disorder (MDD), confirmed by structured clinical interview
- Current moderate-to-severe depressive episode (MADRS score ≥ 20)
- Moderate-to-severe treatment resistance, assessed using the Maudsley Staging Method
- Able to comprehend English sufficiently to complete study procedures and assessments
Key exclusion criteria (7 listed)
- Primary psychiatric diagnosis other than MDD
- Contraindications to MRI (e.g., implanted metal)
- Conditions or medications that may increase risk associated with TMS
- Prior exposure to repetitive TMS (rTMS)
- Non-response to electroconvulsive therapy (ECT)
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 |
|---|---|---|
| Personalized iTBSIntermittent theta burst stimulation delivered to the left dorsolateral prefrontal cortex using individualized pulse count (600, 1200, or 1800 pulses) and intensity (90% or 120% rMT) determined by EL-TEP screening. | Device | Personalized iTBS |
| Non-Personalized iTBSIntermittent theta burst stimulation delivered to the left dorsolateral prefrontal cortex at fixed parameters: 1800 pulses, 120% resting motor threshold. | Device | Non-Personalized iTBS |
| Sham iTBSInactive sham stimulation using a shielded coil with electrical scalp stimulation to mimic sensory experience of active iTBS. | Device | Sham iTBS |
Primary outcome
Percent Change in Early Local TMS-Evoked Potential (EL-TEP) Amplitude
Time frame: Baseline, end of 10 iTBS sessions within a single testing day (10 hours)
EL-TEP amplitude is the peak-to-trough amplitude of the early (20-60 ms) EEG response recorded over the left dorsolateral prefrontal cortex following single TMS pulses. Percent change is calculated from pre-iTBS to post-iTBS for each stimulation condition.
8 secondary outcomes
Acute EL-TEP Suppression Following Each Screened iTBS Condition
Time frame: Baseline, end of each iTBS session during the screening phase (3 screening days, up to approximately 3 weeks)
Trajectory of EL-TEP Change Across Multiple Sessions Within a Testing Day
Time frame: Baseline, before and after sessions 1, 2, 3, and 10 within a single testing day (10 hours)
Change in Montgomery-Åsberg Depression Rating Scale (MADRS) Score
Time frame: Baseline, end of each testing day (up to approximately 7 weeks)
Change in Quick Inventory of Depressive Symptomatology (QIDS) Score
Time frame: Baseline, end of each testing day (up to approximately 7 weeks)
Change in Generalized Anxiety Disorder 7-Item Scale (GAD-7) Score
Time frame: Baseline, end of each testing day (up to approximately 7 weeks)
Change in N-Back Task Performance
Time frame: Baseline, end of each testing day (up to approximately 7 weeks)
Change in Multi-Source Interference Task (MSIT) Performance
Time frame: Baseline, end of each testing day (up to approximately 7 weeks)
Change in Affective Processing Task Performance
Time frame: Baseline, end of each testing day (up to approximately 7 weeks)
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 14 Apr 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
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Personalized iTBS and Non-Personalized iTBS in people with Major Depressive Disorder and Treatment Resistant Depression, run by Stanford University at 1 site 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 6 inclusion and 7 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: opening soon, as of the sponsor's last update on 14 Apr 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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. Some participants in this study may receive a placebo. 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) 831-2366, kellerlab@stanford.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Percent Change in Early Local TMS-Evoked Potential (EL-TEP) Amplitude (time frame: Baseline, end of 10 iTBS sessions within a single testing day (10 hours)). 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 14 Apr 2026.