Closed-loop Optimized rTMS for Depression

NCT04142320 | Completed Phase 1 Results FDA Device

• 2 other identifiers: 60980-1R01MH126639
• Study Type: interventional
• Target: 41
• Locations: 1 country
• Sites: 1

Brief Summary

Targeted and individualized treatments for mental health disorders are critically needed. Repetitive transcranial magnetic stimulation (rTMS) represents the front-line of new and innovative approaches to normalizing dysfunctional brain networks in those with mental illness. rTMS is FDA-approved for depression and obsessive-compulsive disorder with clinical trials underway for PTSD and addiction, among others. However, remission rates are suboptimal and ideal stimulation parameters are unknown. We recently completed a randomized, double blind clinical trial and a depression severity biomarker that predicts clinical outcome. The overarching goal of this study is to develop the first broadly generalizable platform for real-time biomarker monitoring and personalized rTMS treatment. We plan to recruit patients with medication-resistant depression and in perform a four-phase, cross-over, double-blind, placebo-controlled trial to 1) identify how standard and optimized rTMS patterns engage the depression severity biomarker, and 2) determine the dose-response of these rTMS patterns. Findings from this study will provide the basis for a double-blind, randomized clinical trial comparing rTMS optimized to the individual against standard rTMS.

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (1)

• Change in Early-local TMS-evoked Potential (EL-TEP)

  TMS-EEG was used to measure the peak-to-peak amplitude of the TMS-evoked potential between 20-60 milliseconds after single TMS pulses in the left frontoparietal region. Changes in the TMS-evoked EEG response were quantified in decibels (dB) relative to baseline. Measurements were obtained before and after the rTMS intervention to assess neurophysiologic changes associated with target engagement.

  Baseline: ~1 hour before first intervention; Pre-intervention: ~1-15 min before first TBS; Post-intervention: ~1-15 min after last TBS, ~100 min after first TBS.

Study Arms (2)

Personalized rTMS

EXPERIMENTAL

Participants received personalized rTMS using MRI-guided neuronavigation to target the dorsolateral prefrontal cortex (dlPFC). Intermittent theta burst stimulation (iTBS) consisted of 600 pulses delivered over approximately 3.5 minutes at 110% of the participant's resting motor threshold. Participants were monitored throughout each stimulation session for adverse events and side effects.

Device: Neuronavigated rTMS

Sham rTMS

EXPERIMENTAL

Participants may receive sham rTMS using MRI-guided neuronavigation in a crossover design. Sham stimulation was designed to mimic active stimulation while maintaining participant blinding. Participants were monitored throughout each stimulation session for adverse events and side effects.

Device: sham rTMS

Interventions

sham rTMS DEVICE

Delivers placebo magnetic stimulation

Sham rTMS

Neuronavigated rTMS DEVICE

Delivers patterned magnetic stimulation using MRI-guided neuronavigation.

Personalized rTMS

Eligibility Criteria

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

You may qualify if:

• Men and women, ages 18 to 65
• Must comprehend English well to ensure adequate comprehension of the EEG and TMS instructions, and of clinical scales
• Right-handed
• No current or history of neurological disorders
• No seizure disorder or risk of seizures
• No use of PRN medication within 48 hours of the scheduled study appointment

You may not qualify if:

• Those with a contraindication for MRIs (e.g. implanted metal)
• Any unstable medical condition
• History of head trauma with loss of consciousness
• History of seizures
• Neurological or uncontrolled medical disease
• Active substance abuse
• Diagnosis of psychotic or bipolar disorder
• A prior history of ECT or rTMS failure
• Currently taking medications that substantially reduce seizure threshold (e.g., olanzapine, chlorpromazine, lithium)
• Currently pregnant or breastfeeding

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

Condition Hierarchy (Ancestors)

Depressive Disorder; Mood Disorders; Mental Disorders

Results Point of Contact

• Title: Corey Keller, MD, PhD
• Organization: Stanford University

ckeller1@stanford.edu

(650) 498-9111

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NON RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor, Department of Psychiatry and Behavioral Sciences

Study Record Dates

• First Submitted: October 17, 2019
• First Posted: October 29, 2019
• Study Start: June 1, 2021
• Primary Completion: July 10, 2025
• Study Completion: July 10, 2025
• Last Updated: September 29, 2026
• Results First Posted: September 29, 2026

Record last verified: 2026-09

Locations

US (1)