Recruiting
Phase 3

rTMS

Sponsor:

Weill Medical College of Cornell University

Code:

NCT04041479

Conditions

Treatment Resistant Depression

Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 22 - 65

Healthy Volunteers: Not accepted

Interventions

Repetitive Transcranial Magnetic Stimulation

Repetitive Transcranial Magnetic Stimulation

Study Details

Brief summary:

Repetitive transcranial magnetic stimulation (rTMS) is a treatment for depression. The investigators are continuing to learn how to optimize outcomes from rTMS treatment. The purpose of this research project is to use brain network connectivity patterns as measured by resting state functional magnetic resonance imaging (fMRI) to confirm a way to optimize the use of rTMS to treat depression. In addition, the study aims to gain a better understanding of how rTMS influences brain networks.

Conditions

Treatment Resistant Depression

Major Depressive Disorder

Study ID

NCT04041479

Start date

Sep 17, 2021

Status verified date

Feb, 2026

Completion date

Aug, 2027

Anticipated

Primary completion date

Apr, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 22 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Age 22 to 65 years
  • Major Depressive Disorder (by M.I.N.I., Diagnostic Statistical Manual V (DSM-V criteria)); Verification by evaluation by licensed study psychiatrist or psychologist
  • At least moderately severe depression (17-item Hamilton Depression Rating Scale greater than or equal to 18)
  • Failure to respond in the current episode to at least 1 antidepressant medication at an adequate dose and duration as measured by a modified Antidepressant Treatment History Form. The Maudsley Staging Method will also be used to quantify treatment resistance.
  • Any and all medication intended to treat depression or reduce symptoms of depression must be discontinued or maintained at the same daily dose for ≥ 4 weeks prior to enrollment and for the duration of the study
  • Capacity to consent
  • Written consent to allow communication between members of the research team and the patient's outpatient clinician(s) (psychiatrist, psychotherapist, nurse practitioner, primary care physician, or equivalent) as needed to ensure safety
  • Ability to safely participate in MRI
  • Fluent in English

Exclusion Criteria:

  • Imminent risk of suicide (based on the Columbia-Suicide Severity Rating Scale)
  • Current depressive episode greater than or equal to 2 years duration
  • Presence of primary psychiatric diagnoses other than MDD and/or comorbid generalized anxiety disorder (GAD) or phobia (e.g., post-traumatic stress disorder; obsessive-compulsive disorder; MDD w psychotic features; primary psychotic illness; Bipolar I or II)
  • DSM-5 defined addiction to, dependence on, abuse of, or misuse of any substance during the prior 12 months, excluding nicotine
  • Evidence of cognitive impairment (MMSE score falling greater than or equal to 1 SD below the mean score for his or her age and education)
  • Recent onset (within 8 weeks of screening) psychotherapy, including, but not limited to: any form of treatment, aid, or therapy that has intensively and extensively examined the patient's psychological history, including, but not limited to: cognitive behavioral therapy, dialectical behavioral therapy, interpersonal therapy, and family-focused therapy
  • Prior exposure to an adequate dose and duration of the TMS treatment protocol administered in this study during the current depressive episode.
  • Participated in any clinical trial with an investigational drug or device within the past 6 weeks prior to screening
  • History of neurosurgery to treat a neurological or psychiatric disorder
  • Evidence or history of significant neurological disorder, including moderate-severe head trauma, stroke, Parkinson's disease or other movement disorder (except benign essential tremor), epilepsy, history of seizures, cerebrovascular disease, dementia, increased intracranial pressure, history of repetitive or severe head trauma, or primary or secondary tumors within the central nervous system
  • Implanted electronic devices and/or conductive objects in or near the head, including metal plates, aneurysm coils, cochlear implants, ocular implants, deep brain stimulation devices and stents
  • Any implanted device that is activated or controlled in any way by physiological signals, including, but not limited to: deep brain stimulators, cochlear implants, and vagus nerve stimulators
  • Patients with major depressive disorder who have failed to receive clinical benefit from Vagus Nerve Stimulation (VNS) or are currently receiving these therapies.
  • History of seizures (except juvenile febrile seizures) or any condition/concurrent medication that could notably lower seizure threshold
  • Individuals who are pregnant, nursing, contemplating pregnancy within the length of the study or, in the opinion of the investigator, not adherent to a medically acceptable method of birth control
  • History or presence of any disease, medical condition or physical condition that, in the opinion of the investigator, may compromise, interfere, limit, effect, or reduce the participant's ability to complete a treatment study lasting up to 21 weeks
  • Abnormal bloodwork for electrolytes, thyroid and liver function
  • Individuals who are taking > 300 mg daily dose of bupropion in any formulation (immediate, extended, or slow-release)
  • Individuals who are taking tricyclic antidepressants.

Study Design

Enrollment

348 participants

Anticipated

Allocation

Randomized

Intervention Model

Parallel Assignment

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Standard of Care

FDA-cleared, standard-of-care iTBS repetitive Transcranial Magnetic Stimulation targeting the left dorsolateral prefrontal cortex (DLPFC), regardless of the depression subtype (biotype) determined by a magnetic resonance imaging (MRI) scan.

experimental: Targeted Side Arm

iTBS rTMS targeting the area of the brain (DLPFC or dorsomedial prefrontal cortex DMPFC)) that we hypothesize will be most effective for that subject's biotype (confirmation arm).

active comparator: Opposite Side Arm

iTBS rTMS targeting the opposite site (DLPFC or DMPFC) than the one we hypothesize will be most effective for that subject's biotype (disconfirmation arm).

Interventions

Repetitive Transcranial Magnetic Stimulation

iTBS rTMS targeting the DMPFC or left DLPFC

Repetitive Transcranial Magnetic Stimulation

iTBS rTMS targeting the left DLPFC

Primary outcome measure

  • Change in depression, as measured by the Hamilton Depression Rating Scale (HAMD17) [ Time Frame: Baseline and 1 Week Post Treatment (8-10 weeks) ]

Central Contacts and Locations

Central contacts

Megan Johnson

646-962-2900tmsinfo@med.cornell.edu

Lindsay Victoria, PhD

liv3002@med.cornell.edu

Locations

Stanford University

Recruiting

Stanford, California, United States, 94305

Contacts

Derrick Buchanan, PhD

dmbuchan@stanford.edu

Weill Cornell Medicine

Recruiting

New York, New York, United States, 10065

Contacts

Conor Liston, MD, PhD

(646) 962-6293col2004@med.cornell.edu

More Information

Sponsor

Weill Medical College of Cornell University

Last update posted

Feb 25, 2026

Last verified

Feb, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Weill Medical College of Cornell University on 2026-02-25.