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NCT Number: NCT07528157

Early Brainwave Biomarkers for Personalized Neuromodulation in Treatment-resistant Depression

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.

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Key information

Conditions

Major Depressive Disorder Depressive Disorder Depressive Disorder, Major Depressive Disorder, Treatment-Resistant Mental Disorders Mood Disorders Treatment Resistant Depression

Age range

18 year–65 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Stanford University

Stanford, California, 94305, United States

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Personalized iTBS

Device

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 iTBS

Device

Intermittent theta burst stimulation delivered to the left dorsolateral prefrontal cortex at fixed parameters: 1800 pulses, 120% resting motor threshold.

Sham iTBS

Device

Inactive sham stimulation using a shielded coil with electrical scalp stimulation to mimic sensory experience of active iTBS.

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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).

  4. 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).

  5. 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).

  6. 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.

  7. 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.

  8. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Jade T Truong, BS

CONTACT

[email protected]

(408) 831-2366

Sponsors and collaborators

Lead sponsor

Stanford University

Other

Collaborators

  • National Institute of Mental Health (NIMH)

Registry information

Official study title

Early TMS-EEG Potentials as Biomarkers for Personalized Neuromodulation in Treatment-Resistant Depression (R61 Phase)

Important dates

Study start
2026
Primary completion
2027
Study completion
2027
First posted
Apr 14, 2026
Registry last updated
Apr 14, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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