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Not recruiting

rTMS

Sponsor:

Stanford University

Code:

NCT04142320

Conditions

Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

closed-loop rTMS

open-loop rTMS

sham rTMS

Study Details

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

Study ID

NCT04142320

Start date

Jun 1, 2021

Status verified date

Nov, 2025

Completion date

Dec 1, 2025

Anticipated

Primary completion date

Aug 30, 2025

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • 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

Exclusion Criteria:

  • 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

Study Design

Enrollment

54 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Basic Science

Interventions and Outcome Measures

Arms

experimental: Closed-loop rTMS

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.

active comparator: Open-loop rTMS

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.

placebo comparator: Sham rTMS

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.

Interventions

closed-loop rTMS

Delivers patterned magnetic stimulation in closed-loop fashion

open-loop rTMS

Delivers patterned magnetic stimulation in open-loop fashion

sham rTMS

Delivers placebo magnetic stimulation

Primary outcome measure

  • Transcranial Magnetic Stimulation (TMS) / Electroencephalography (EEG) change [ Time Frame: Up to 2 hours ]

Central Contacts and Locations

Central contacts

Corey Keller, MD, PhD

(650) 498-9111ckeller1@stanford.edu

Locations

Stanford University

Recruiting

Stanford, California, United States, 94305

Contacts

Jade Truong

kellerlab@stanford.edu

More Information

Sponsor

Stanford University

Last update posted

Nov 13, 2025

Last verified

Nov, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-16. This information was provided to ClinicalTrials.gov by Stanford University on 2025-11-13.