Early Brainwave Biomarkers for Personalized Neuromodulation in Treatment-resistant Depression

N/ANot Yet RecruitingNCT07528157

Stanford University80 enrolled

Overview

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 Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Major Depressive Disorder Treatment Resistant Depression

Interventions

Eligibility

Sex: ALLMin age: 18 YearsMax age: 65 Years

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

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.

Time frame: Baseline, end of 10 iTBS sessions within a single testing day (10 hours)

Secondary Outcomes

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.

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

EL-TEP amplitude measured before and after sessions 1, 2, 3, and 10 on each testing day to characterize cumulative effects.

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

Clinician-administered scale assessing depressive symptom severity. Score range: 0-60 (higher scores indicate greater severity).