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

Not yet recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

80

Phase

  • 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 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

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
Intervention / Treatment
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

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

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

Stanford University

Collaborators

National Institute of Mental Health (NIMH)

Investigators

  • 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)

June 1, 2026

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2027

Study Registration Dates

First Submitted

April 7, 2026

First Submitted That Met QC Criteria

April 7, 2026

First Posted (Actual)

April 14, 2026

Study Record Updates

Last Update Posted (Actual)

April 14, 2026

Last Update Submitted That Met QC Criteria

April 7, 2026

Last Verified

April 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID 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.

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