NCT05523817

Brief Summary

Repetitive transcranial magnetic stimulation (rTMS) is a way of non-invasively stimulating specific brain networks and is an established treatment for Major Depressive Disorder (MDD). This proposal will reveal network mechanisms of the therapeutic effects of rTMS by investigating how stimulating each network specifically changes network connectivity and behavior. This will be done in a highly individualized manner in depressed and healthy patients, leading to more effective and more individualized treatments for depression.

Trial Health

77
On Track

Trial Health Score

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

Enrollment
80

participants targeted

Target at P50-P75 for not_applicable major-depressive-disorder

Timeline
32mo left

Started Mar 2024

Longer than P75 for not_applicable major-depressive-disorder

Geographic Reach
1 country

1 active site

Status
recruiting

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

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Progress46%
Mar 2024Dec 2028

First Submitted

Initial submission to the registry

August 14, 2022

Completed
17 days until next milestone

First Posted

Study publicly available on registry

August 31, 2022

Completed
1.5 years until next milestone

Study Start

First participant enrolled

March 12, 2024

Completed
3.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

December 31, 2027

Expected
1 year until next milestone

Study Completion

Last participant's last visit for all outcomes

December 31, 2028

Last Updated

September 29, 2025

Status Verified

September 1, 2025

Enrollment Period

3.8 years

First QC Date

August 14, 2022

Last Update Submit

September 24, 2025

Conditions

Major Depressive Disorder

Outcome Measures

Primary Outcomes (14)

  • Resting-state functional connectivity (FC)

    Changes in connectivity within and between brain networks

    1 hour

  • Blood oxygenation level dependent (BOLD) activation

    Changes in activation resulting from performing a specific functional MRI (fMRI) task

    1 hour

  • Applied Cognition-General Concerns scale

    Subjects rate how statements about cognition and attention apply to them, e.g., "Thinking is foggy." Score range is 8-40, with higher scores indicating lesser cognitive concerns.

    10 minutes

  • Profile of Mood States Tension subscale

    Subjects are asked to rate how much certain adjectives about their mood apply to them at that moment, e.g., "tense", "nervous", "shaky." Score range: 0-28, higher scores indicating more tension.

    5 minutes

  • Profile of Mood States Vigor subscale

    Subjects rate how much mood adjectives apply to them at that moment, e.g., "full of pep," "energetic," "vigorous." Score range 0-28, higher scores indicating more vigor.

    5 minutes

  • Profile of Mood States Dejection subscale

    Subjects rate how much mood adjectives apply to them at that moment, e.g., "unworthy." Score range 0-28, higher scores indicating higher dejection.

    5 minutes

  • State Shame and Guilt Scale

    Subjects rate how much certain statements apply to them, e.g., "I feel regret." Score range is 10-50, higher scores indicate more shame/guilt.

    5-10 minutes

  • Fawcett-Clark Pleasure Capacity Scale

    Subjects anticipate how much they would enjoy a certain scenario, e.g., "you sit watching a beautiful sunset in an isolated part of the world." Score range is 36 to 180, higher scores indicate higher pleasure capacity.

    5-10 minutes

  • Digit-Span Test

    Subjects repeat number lists in forward or reverse order (maximum score is 8 forwards and 8 backwards, higher scores indicate better performance).

    5 minutes

  • Tower of London Task

    Subjects plan a series of moves to match a start set to a goal set.

    5-10 minutes

  • Delayed Match to Sample Task

    Subjects match patterns to a recently viewed sample pattern. Score ranges from 0-30, with higher scores indicating better performance.

    5 minutes

  • The Simon Test

    Subjects press different buttons based on incongruent spatial and/or color cues. Scores range from 0-30, with higher scores indicating better performance.

    5 minutes

  • Face-name Associative Paradigm

    Subjects must remember names paired with certain faces (DN-A). Scores range from 0-32, with higher scores indicating better performance.

    30 minutes

  • Reading the Mind Through the Eyes Test

    Subjects judge another person's mental state by looking at pictures of only their eyes. Score ranges from 0-41, higher scores indicate better performance.

    10 minutes

Study Arms (6)

DLPFC Salience network target

EXPERIMENTAL

iTBS delivered four times daily to an individually defined salience network representation in left dorsolateral prefrontal cortex (DLPFC).

Device: Intermittent Theta Burst Stimulation (iTBS)

DLPFC Control network target

EXPERIMENTAL

iTBS delivered four times daily to an individually defined control network representation in left dorsolateral prefrontal cortex (DLPFC).

Device: Intermittent Theta Burst Stimulation (iTBS)

DLPFC Default network A target

EXPERIMENTAL

iTBS delivered four times daily to an individually defined default network A representation in left dorsolateral prefrontal cortex (DLPFC).

Device: Intermittent Theta Burst Stimulation (iTBS)

dmPFC Default network B target

EXPERIMENTAL

iTBS delivered four times daily to an individually defined default network B representation in left dorsomedial prefrontal cortex (DMPFC).

Device: Intermittent Theta Burst Stimulation (iTBS)

vmPFC limbic-reward network target

EXPERIMENTAL

iTBS delivered four times daily to an individually defined reward network representation in left ventromedial prefrontal cortex (vMPFC).

Device: Intermittent Theta Burst Stimulation (iTBS)

SHAM stimulation

SHAM COMPARATOR

SHAM iTBS delivered four times daily to an individually defined SHAM region in left dorsolateral prefrontal cortex (DLPFC).

Device: Intermittent Theta Burst Stimulation (iTBS)

Interventions

Intermittent Theta Burst Stimulation (iTBS)DEVICE

iTBS is a form of non-invasive brain stimulation used to treat depression. It works on the principles of electromagnetic induction.

Also known as: Repetitive Transcranial Magnetic Stimulation
DLPFC Control network targetDLPFC Default network A targetDLPFC Salience network targetSHAM stimulationdmPFC Default network B targetvmPFC limbic-reward network target

Eligibility Criteria

Age18 Years - 65 Years
Sexall
Healthy VolunteersYes
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • years of age
  • Capacity to provide informed consent form to participate in the study
  • years of age
  • Capacity to provide informed consent form to participate in the study
  • Currently in a major depressive episode. Comorbid anxiety disorders and personality disorders will be allowed provided that MDD is the primary diagnosis.

You may not qualify if:

  • Meeting criteria, in the past or currently, for bipolar affective disorder, hypomania or mania.
  • Meeting criteria, in the past or currently, for a primary psychotic disorder (e.g., schizophrenia).
  • Neurological conditions with known structural brain lesions, e.g., intracranial masses, multiple sclerosis.
  • Any personal history of seizures or a family history of epilepsy in a first-degree relative.
  • Metal in the body that is ferromagnetic or metallic injury to the eyes.
  • Implanted pacemakers, medication pumps, vagal stimulators, deep brain stimulators, or ventriculoperitoneal shunts, etc.
  • Substance abuse or dependence that is current and active within the last six months, as indicated by self-report (e.g., heroin, cocaine, methamphetamines).
  • Inability to meet the safety criteria for MRI scanning for any other reason.
  • Severe or unstable medical illness.
  • Currently pregnant, as assessed with urine pregnancy test in women of childbearing age.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Massachusetts General Hospital

Boston, Massachusetts, 02129, United States

RECRUITING

Related Publications (2)

  • Eldaief MC, Halko MA, Buckner RL, Pascual-Leone A. Transcranial magnetic stimulation modulates the brain's intrinsic activity in a frequency-dependent manner. Proc Natl Acad Sci U S A. 2011 Dec 27;108(52):21229-34. doi: 10.1073/pnas.1113103109. Epub 2011 Dec 12.

    PMID: 22160708BACKGROUND

  • Fox MD, Halko MA, Eldaief MC, Pascual-Leone A. Measuring and manipulating brain connectivity with resting state functional connectivity magnetic resonance imaging (fcMRI) and transcranial magnetic stimulation (TMS). Neuroimage. 2012 Oct 1;62(4):2232-43. doi: 10.1016/j.neuroimage.2012.03.035. Epub 2012 Mar 19.

    PMID: 22465297BACKGROUND

MeSH Terms

Conditions

Depressive Disorder, Major

Interventions

Transcranial Magnetic Stimulation

Condition Hierarchy (Ancestors)

Depressive DisorderMood DisordersMental Disorders

Intervention Hierarchy (Ancestors)

Magnetic Field TherapyTherapeutics

Study Design

Study Type
interventional
Phase
not applicable
Allocation
NON RANDOMIZED
Masking
DOUBLE
Who Masked
PARTICIPANT, OUTCOMES ASSESSOR
Masking Details
Participants will receive active or sham stimulation and will be blinded as to the stimulation type.
Purpose
OTHER
Intervention Model
CROSSOVER
Model Details: Within-subject crossover study
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Assistant Professor of Neurology

Study Record Dates

First Submitted

August 14, 2022

First Posted

August 31, 2022

Study Start

March 12, 2024

Primary Completion (Estimated)

December 31, 2027

Study Completion (Estimated)

December 31, 2028

Last Updated

September 29, 2025

Record last verified: 2025-09

Data Sharing

IPD Sharing
Will not share

This project will adhere to the NIH Grant Policy on Sharing of Unique Research Resources including the Principles and Guidelines for Recipients of NIH Research Grants and Contracts on Obtaining and Disseminating Biomedical Research Resources. The results of this research will be made available via publication in scientific journals and through scientific meetings where our findings are reported. Publication of data shall occur during the project, if appropriate, or at the end of the project, consistent with normal scientific practices. All publications will be made publicly available consistent with NIH policies. Such research data will be redacted to prevent the disclosure of personal identifiers.

Locations

US(1)