Actively Recruiting

Phase 3
Age: 22Years - 65Years
All Genders
ID04041479

Efficacy of Biomarker-guided rTMS for Treatment Resistant Depression

Led by Weill Medical College of Cornell University · Updated on 2026-02-25

348

Participants Needed

2

Research Sites

17 weeks

Total Duration

On this page

Sponsors

W

Weill Medical College of Cornell University

Lead Sponsor

N

National Institute of Mental Health (NIMH)

Collaborating Sponsor

AI-Summary

What this Trial Is About

Researchers are investigating the use of repetitive transcranial magnetic stimulation (rTMS) to treat patients with treatment-resistant depression, a condition where standard antidepressant medications have failed. This study aims to confirm whether a new approach using brain connectivity patterns measured by resting state functional MRI (fMRI) can improve how rTMS is targeted to different brain areas for better outcomes. The study also seeks to understand how rTMS affects brain networks in these patients. Participants will be randomly assigned to one of three groups: one receiving standard rTMS targeting the left dorsolateral prefrontal cortex (DLPFC), another receiving rTMS targeted to the brain area predicted to be most effective for their depression subtype based on brain imaging (either DLPFC or dorsomedial prefrontal cortex, DMPFC), and a third group receiving rTMS targeting the opposite brain area than predicted. The treatment uses intermittent theta burst stimulation (iTBS) delivered at 120% of the resting motor threshold in short bursts totaling about 3 minutes per session. Throughout the study, participants will undergo brain scans, behavioral tests, and clinical assessments before and after the treatment period of 7 to 10 weeks. The main measure of success is the change in depression severity using a standard rating scale. Researchers will also monitor changes in brain connectivity and other depression symptom scores. Safety and treatment effects will be closely observed during the trial, which lasts up to 21 weeks including follow-up.

CONDITIONS

Brief Title

Biomarker-guided rTMS for Treatment Resistant Depression

Who Can Participate

Age: 22Years - 65Years
All Genders

Eligibility Criteria

Eligible

You may qualify if you...

  • Age 22 to 65 years
  • Diagnosis of Major Depressive Disorder confirmed by a licensed psychiatrist or psychologist using DSM-V criteria
  • At least moderately severe depression (Hamilton Depression Rating Scale score of 18 or higher)
  • Failure to respond to at least one antidepressant medication during the current depressive episode
  • Stable or discontinued depression-related medications for at least 4 weeks prior to enrollment and during the study
  • Capacity to consent and agree to communication between research team and outpatient clinicians
  • Ability to safely participate in MRI
  • Fluent in English
Not Eligible

You will not qualify if you...

  • Imminent risk of suicide
  • Current depressive episode lasting 2 years or longer
  • Primary psychiatric diagnoses other than Major Depressive Disorder or certain comorbid anxiety disorders
  • Substance misuse or addiction (excluding nicotine) within the past 12 months
  • Evidence of cognitive impairment
  • Recent start of intensive psychotherapy within 8 weeks
  • Prior adequate exposure to the rTMS treatment protocol used in this study during current episode
  • Participation in another clinical trial with investigational drug or device within 6 weeks
  • History of neurosurgery for neurological or psychiatric disorders
  • Significant neurological disorders or history increasing seizure risk
  • Implanted electronic or conductive devices near the head
  • Failure to benefit from or current use of Vagus Nerve Stimulation therapy
  • Pregnancy, nursing, or not using acceptable birth control
  • Medical conditions that may limit ability to complete the study
  • Abnormal blood tests for electrolytes, thyroid or liver function
  • Use of high-dose bupropion or tricyclic antidepressants during the study period
  • History of seizures except juvenile febrile seizures or medications lowering seizure threshold
  • Other conditions judged by the investigator to interfere with study participation

AI-Screening

AI-Powered Screening

Complete this quick 3-step screening to check your eligibility

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Your Study Journey

Screening

Duration - 2 to 4 weeks

Participants are screened for eligibility to participate in the trial.

1 visit (in-person)

Implementation

Duration - 7 to 9 weeks

Participants receive repetitive transcranial magnetic stimulation (rTMS) targeting either the left dorsolateral prefrontal cortex (DLPFC) or the dorsomedial prefrontal cortex (DMPFC) based on random assignment to one of three study arms.

Daily visits for up to 9 weeks

Follow-up

Duration - Up to 1 week post treatment

After completing treatment, participants are assessed for changes in depression symptoms and brain connectivity using clinical scales and fMRI scans.

1 visit (in-person)

Trial Site Locations

Total: 2 locations

1

Stanford University

Stanford, California, United States, 94305

Actively Recruiting

2

Weill Cornell Medicine

New York, New York, United States, 10065

Actively Recruiting

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Research Team

M

Megan Johnson

L

Lindsay Victoria, PhD

How is the study designed?

Study Type

INTERVENTIONAL

Masking

QUADRUPLE

Allocation

RANDOMIZED

Model

PARALLEL

Primary Purpose

TREATMENT

Number of Arms

3

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