Early Brainwave Biomarkers for Personalized Neuromodulation in Treatment-resistant Depression

April 7, 2026 updated by: Corey Keller, Stanford University

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Not yet recruiting

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Estimated)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
80

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact

The name and contact information for the person who can answer enrollment questions for a clinical study. Each location where the study is being conducted may also have a specific contact, who may be better able to answer those questions.

Study Locations

  • United States
    • California
      • Stanford, California, United States, 94305
        • Stanford University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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)

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Experimental: Personalized iTBS
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.
Device: Personalized iTBS
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.
Active Comparator: Non-Personalized iTBS
Participants receive 10 sessions of iTBS using standard fixed parameters (1800 pulses, 120% resting motor threshold).
Device: Non-Personalized iTBS
Intermittent theta burst stimulation delivered to the left dorsolateral prefrontal cortex at fixed parameters: 1800 pulses, 120% resting motor threshold.
Sham Comparator: Sham iTBS
Participants receive 10 sessions of sham iTBS, matched in timing and scalp sensation to active stimulation using a shielded coil and scalp electrodes.
Device: Sham iTBS
Inactive sham stimulation using a shielded coil with electrical scalp stimulation to mimic sensory experience of active iTBS.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
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.
Baseline, end of 10 iTBS sessions within a single testing day (10 hours)

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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)
Percent change in EL-TEP amplitude from before to after each of the six screened iTBS parameter combinations during the screening phase.
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)
EL-TEP amplitude measured before and after sessions 1, 2, 3, and 10 on each testing day to characterize cumulative effects.
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)
Clinician-administered scale assessing depressive symptom severity. Score range: 0-60 (higher scores indicate greater severity).
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)
Self-report measure of depressive symptom severity. Score range: 0-27 (higher scores indicate greater severity).
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)
Self-report measure of anxiety symptom severity. Score range: 0-21 (higher scores indicate greater severity).
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)
Working memory performance assessed using the N-back task. Outcome is accuracy and reaction time.
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)
Executive function assessed using the MSIT. Outcome is accuracy and reaction time.
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)
Emotional face recognition task performance. Outcome is accuracy.
Baseline, end of each testing day (up to approximately 7 weeks)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Stanford University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
National Institute of Mental Health (NIMH)

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Principal Investigator: Corey J Keller, MD, PhD, Stanford University

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Estimated)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2026

Primary Completion (Estimated)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 31, 2027

Study Completion (Estimated)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 31, 2027

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
April 7, 2026

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2026

First Posted (Actual)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
April 14, 2026

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
April 14, 2026

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
April 7, 2026

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 85003-1
  • R61MH140799 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

Yes

product manufactured in and exported from the U.S.

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings