Closed-loop Optimized rTMS for Depression

Phase

N/A

Condition

Depression (Major/severe)

Affective Disorders

Mood Disorders

Treatment

sham rTMS

open-loop rTMS

closed-loop rTMS

Clinical Study ID

NCT04142320

60980-1

R01MH126639

Ages 18-65
All Genders

Study 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.

Eligibility Criteria

Inclusion

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 TMSinstructions, 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

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

sham rTMS

June 01, 2021

December 01, 2025

Study Description

Nearly 50% of all Americans will suffer from a mental health disorder during their lifetimes. Brain stimulation treatments, including repetitive transcranial magnetic stimulation (rTMS), are increasingly used to normalize dysfunctional brain circuits in these disorders. Mechanistically, rTMS is thought to work by changing the synaptic strength of neurons, referred to as brain plasticity. Despite the variety of disorders targeted and significant between-patient heterogeneity, rTMS is currently applied in a manner that is one-size-fits-all (without any individual optimization of the stimulation pattern) and open-loop (fixed schedule of stimulation pattern, with no measurement or adjustment during rTMS). We believe that the response rate of rTMS for depression, which is at present <50%, can be improved through personalized brain stimulation that enhances target engagement and maximizes plasticity. To personalize brain stimulation, one must (1) measure and monitor brain changes in real-time; (2) determine the optimal stimulation patterns for inducing brain changes; (3) develop adaptive treatments to drive desired changes on an individual patient-specific level over time. Such personalization of brain stimulation will increase our mechanistic understanding of brain plasticity to improve efficacy in non-responders to standard treatments.

The primary goals of my research program are to (1) discover brain biomarkers that predict progression to clinical remission, and (2) develop closed-loop treatment algorithms that optimize these biomarkers and improve clinical outcomes. We will focus on depression as it is the leading cause of disability worldwide and and medications are ineffective or not tolerated for close to half of these patients. Leveraging my previous work, we propose three stages of development of personalized brain stimulation using single pulses of TMS combined with electroencephalography (TMS-EEG) to generate a causal measurement of brain state that can easily be translated to the clinic. The TMS-EEG depression severity biomarker that I recently discovered occurs 30 milliseconds after administering a TMS test pulse (p30) in the fronto-parietal network (FPN), a region implicated in depression. The degree of suppression of this p30 signal predicted clinical outcome in depressed patients following rTMS treatment. Additionally, a single stimulation session was sufficient to suppress the p30 during and for 30 minutes after stimulation. This work indicates that p30 suppression can be monitored in real-time and has the potential to support empiric treatment optimization.

Findings from this study will provide the basis for a double-blind, randomized clinical trial of closed-loop rTMS against standard rTMS.

Connect with a study center

Stanford University
Stanford, California 94305
United States
Site Not Available
Stanford University
Stanford 5398563, California 5332921 94305
United States
Active - Recruiting

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