NCT04041479

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.

Trial Health

77
On Track

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
348

participants targeted

Target at P50-P75 for phase_3

Timeline
14mo left

Started Sep 2021

Longer than P75 for phase_3

Geographic Reach
1 country

2 active sites

Status
recruiting

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

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Study Timeline

Key milestones and dates

Study Progress80%
Sep 2021Aug 2027

First Submitted

Initial submission to the registry

July 31, 2019

Completed
1 day until next milestone

First Posted

Study publicly available on registry

August 1, 2019

Completed
2.1 years until next milestone

Study Start

First participant enrolled

September 17, 2021

Completed
5.5 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

April 1, 2027

Expected
4 months until next milestone

Study Completion

Last participant's last visit for all outcomes

August 1, 2027

Last Updated

February 25, 2026

Status Verified

February 1, 2026

Enrollment Period

5.5 years

First QC Date

July 31, 2019

Last Update Submit

February 24, 2026

Conditions

Outcome Measures

Primary Outcomes (1)

  • Change in depression, as measured by the Hamilton Depression Rating Scale (HAMD17)

    The Hamilton Depression Rating Scale (HAMD17) is a 17 item clinician-rated measure of depression severity. Scores of 0-7 = Normal, 8-13 = Mild Depression, 14-18 = Moderate Depression, 19-22 = Severe Depression, ≥ 23 = Very Severe Depression

    Baseline and 1 Week Post Treatment (8-10 weeks)

Secondary Outcomes (2)

  • Change in depression, as measured by the Quick Inventory of Depressive Symptomology (QIDS)

    Baseline and Post Treatment (7-9 weeks)

  • Change in Resting State fMRI Connectivity

    Baseline and after completion of treatment (7-9 weeks)

Study Arms (3)

Standard of Care

ACTIVE COMPARATOR

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.

Device: Repetitive Transcranial Magnetic Stimulation

Targeted Side Arm

EXPERIMENTAL

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).

Device: Repetitive Transcranial Magnetic Stimulation

Opposite Side Arm

ACTIVE COMPARATOR

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).

Device: Repetitive Transcranial Magnetic Stimulation

Interventions

iTBS rTMS targeting the DMPFC or left DLPFC

Opposite Side ArmTargeted Side Arm

Eligibility Criteria

Age22 Years - 65 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • 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

You may not qualify if:

  • 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
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (2)

Stanford University

Stanford, California, 94305, United States

RECRUITING

Weill Cornell Medicine

New York, New York, 10065, United States

RECRUITING

MeSH Terms

Conditions

Depressive Disorder, Treatment-ResistantDepressive Disorder, Major

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeutics

Study Officials

  • Conor Liston, MD, PhD

    Weill Medical College of Cornell University

    PRINCIPAL INVESTIGATOR

Central Study Contacts

Lindsay Victoria, PhD

CONTACT

Study Design

Study Type
interventional
Phase
phase 3
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
TREATMENT
Intervention Model
PARALLEL
Model Details: Human subjects in the proposed protocol will be randomized to receive a) biotype-guided rTMS to the left DLPFC or to the DMPFC; b) rTMS targeted to the opposite site; and c) standard-of-care left DLPFC rTMS. The dosage and method of delivery of rTMS are as follows: intermittent theta burst stimulation (iTBS) will be delivered at 120% of the resting motor threshold. It will be administered in triplet 50 Hz bursts, repeated at 5 Hz with a duty cycle of 2 s on and 8 s off, for a total of 600 pulses per session and a total duration of 3 min 9 s. Participants will receive screening and diagnostic interviews, phenotypic assessment (including demographic information, cognitive assessments, and behavioral functioning), structured clinical interviews, and magnetic resonance imaging (including structural and functional MRI).
Sponsor Type
OTHER
Responsible Party
SPONSOR

Study Record Dates

First Submitted

July 31, 2019

First Posted

August 1, 2019

Study Start

September 17, 2021

Primary Completion (Estimated)

April 1, 2027

Study Completion (Estimated)

August 1, 2027

Last Updated

February 25, 2026

Record last verified: 2026-02

Data Sharing

IPD Sharing
Will share

In accordance with NIH policy we will share our data via the National Database for Clinical Trials related to Mental Illness (NDCT). NDCT is a secure data platform that will allow us to share research data and tools from our analysis of resting-state fMRI data, task-based fMRI data, and fMRI-guided rTMS data. Specifically, data to be shared will include de-identified neuroimaging scans and rTMS targeting data, in addition to phenotypic data such as demographics, diagnosis, treatment history, and anonymized, item-level responses to clinical and cognitive assessments. These data will then be made available through the NDCT, and NIH-funded repository that ensures that data are secure and shared in accord with applicable NIH regulations.

Time Frame
Raw data (e.g., MRI data and assessment responses) will be deposited on the NDCT every six months (January 15 and June 15 of each year of the award period), in accordance with NIH policy for use of the NDCT in clinical trials research. Curated data will be uploaded annually beginning in the third year of the project.
Access Criteria
The data may be shared with researchers at institutions with a Federal Wide Assurance, who will be able to gain access to NDCT data by submitting a data access request, in line with NDCT policies.

Locations