Early Brainwave Biomarkers for Personalized Neuromodulation in Treatment-resistant Depression

NCT07528157 | Not Yet Recruiting DMC FDA Device

• 2 other identifiers: 85003-1R61MH140799
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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 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.

Conditions

Major Depressive Disorder; Treatment Resistant Depression

Keywords

tms; eeg

Outcome Measures

Primary Outcomes (1)

• 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.

  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

  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

  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

  Baseline, end of each testing day (up to approximately 7 weeks)

• Change in Quick Inventory of Depressive Symptomatology (QIDS) Score

  Baseline, end of each testing day (up to approximately 7 weeks)

• Change in Generalized Anxiety Disorder 7-Item Scale (GAD-7) Score

  Baseline, end of each testing day (up to approximately 7 weeks)

Study Arms (3)

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.

Device: Personalized iTBS

Non-Personalized iTBS

ACTIVE COMPARATOR

Participants receive 10 sessions of iTBS using standard fixed parameters (1800 pulses, 120% resting motor threshold).

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.

Device: Sham iTBS

Interventions

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.

Personalized iTBS

Sham iTBS DEVICE

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

Sham iTBS

Non-Personalized iTBS DEVICE

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

Non-Personalized iTBS

Eligibility Criteria

• Age: 18 Years - 65 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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)

Sponsors & Collaborators

• Stanford University: lead
• National Institute of Mental Health (NIMH): collaborator

Study Sites (1)

Stanford University

Stanford, California, 94305, United States

Location

MeSH Terms

Conditions

Depressive Disorder, Major; Depressive Disorder, Treatment-Resistant

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Study Officials

• Corey J Keller, MD, PhD

  Stanford University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Jade T Truong, BS

CONTACT

(408) 831-2366; kellerlab@stanford.edu

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor

Model Details: All participants receive all three arms.

Study Record Dates

• First Submitted: April 7, 2026
• First Posted: April 14, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): December 31, 2027
• Study Completion (Estimated): December 31, 2027
• Last Updated: April 14, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)