Closed-loop Optimized rTMS for Depression

NCT04142320 | Completed Phase 1 FDA Device

• 2 other identifiers: 60980-1R01MH126639
• Study Type: interventional
• Target: 44
• 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)

• Transcranial Magnetic Stimulation (TMS) / Electroencephalography (EEG) change

  Change in TMS-EEG measures will be assessed before, during, and after each rTMS session. Specifically, the amplitude of the change 30ms after a single TMS pulse in the frontoparietal region will be quantified. Brain changes will be compared between closed- loop, open-loop, and sham rTMS to identify the location, strength, and dose response of change for each condition.

  Up to 2 hours

Study Arms (3)

Closed-loop rTMS

EXPERIMENTAL

Closed-loop rTMS will be delivered to determine the target engagement compared to open-loop rTMS. Closed loop rTMS will be applied for two consecutive days for 30 minutes to determine dose response. Closed- loop rTMS will be delivered using neuro-navigation based on participants' own MRI images. rTMS will last approximately 30 minutes (3000 pulses total) and will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the rTMS session for adverse events and/or side effects.

Device: closed-loop rTMS

Open-loop rTMS

ACTIVE COMPARATOR

A series of open-loop rTMS protocols will be delivered to determine the most effective standard and individualized rTMS. Active rTMS will be delivered using neuro-navigation based on participants' own MRI images. For each clinically-utilized rTMS protocol (1Hz, 5Hz, 10Hz, 20Hz), 3000 pulses will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the rTMS session for adverse events and/or side effects.

Device: open-loop rTMS

Sham rTMS

PLACEBO COMPARATOR

Sham rTMS will be delivered for two consecutive sessions to mimic active rTMS conditions. To maximize sham validity, both 1) a direction- sensor TMS coil will alert the operators to flip the coil if the wrong side is being used, and 2) low-intensity electrical stimulation to match the active rTMS frequency will be applied to scalp electrodes under the coil for sham and placed but not activated in the active arm. The rTMS coil will be positioned using neuro-navigation based on participants' own MRI images, mimicking active rTMS. Sham rTMS will last approximately 30 minutes (3000 pulses total) and will be delivered at 120% of the participant's motor threshold. Participants will be monitored during the sham rTMS session for adverse events and/or side effects.

Device: sham rTMS

Interventions

closed-loop rTMS DEVICE

Delivers patterned magnetic stimulation in closed-loop fashion

Closed-loop rTMS

open-loop rTMS DEVICE

Delivers patterned magnetic stimulation in open-loop fashion

Open-loop rTMS

sham rTMS DEVICE

Delivers placebo magnetic stimulation

Sham 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
• Depression assessed through phone screen
• Not currently on antidepressant medications
• 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

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• 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: April 13, 2026

Record last verified: 2026-04

Locations

US (1)