Recruiting

Depression Treatment

Sponsor:

Massachusetts General Hospital

Code:

NCT05523817

Conditions

Major Depressive Disorder

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

Interventions

Intermittent Theta Burst Stimulation (iTBS)

Study Details

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.

Conditions

Major Depressive Disorder

Study ID

NCT05523817

Start date

Mar 12, 2024

Status verified date

Sep, 2025

Completion date

Dec 31, 2028

Anticipated

Primary completion date

Dec 31, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Accepted

Inclusion Criteria for healthy participants:

  • 18-65 years of age
  • Capacity to provide informed consent form to participate in the study

Inclusion Criteria for participants with Major Depressive Disorder (MDD):

  • 18-65 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.

Exclusion Criteria for all participants:

  • 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.

Study Design

Enrollment

80 participants

Anticipated

Allocation

Non randomized

Intervention Model

Crossover

Primary purpose

Other

Interventions and Outcome Measures

Arms

experimental: DLPFC Salience network target

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

experimental: DLPFC Control network target

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

experimental: DLPFC Default network A target

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

experimental: dmPFC Default network B target

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

experimental: vmPFC limbic-reward network target

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

sham comparator: SHAM stimulation

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

Interventions

Intermittent Theta Burst Stimulation (iTBS)

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

Primary outcome measure

  • Resting-state functional connectivity (FC) [ Time Frame: 1 hour ]
  • Blood oxygenation level dependent (BOLD) activation [ Time Frame: 1 hour ]
  • Applied Cognition-General Concerns scale [ Time Frame: 10 minutes ]
  • Profile of Mood States Tension subscale [ Time Frame: 5 minutes ]
  • Profile of Mood States Vigor subscale [ Time Frame: 5 minutes ]
  • Profile of Mood States Dejection subscale [ Time Frame: 5 minutes ]
  • State Shame and Guilt Scale [ Time Frame: 5-10 minutes ]
  • Fawcett-Clark Pleasure Capacity Scale [ Time Frame: 5-10 minutes ]
  • Digit-Span Test [ Time Frame: 5 minutes ]
  • Tower of London Task [ Time Frame: 5-10 minutes ]
  • Delayed Match to Sample Task [ Time Frame: 5 minutes ]
  • The Simon Test [ Time Frame: 5 minutes ]
  • Face-name Associative Paradigm [ Time Frame: 30 minutes ]
  • Reading the Mind Through the Eyes Test [ Time Frame: 10 minutes ]

Central Contacts and Locations

Locations

Massachusetts General Hospital

Recruiting

Boston, Massachusetts, United States, 02129

Contacts

Mark Eldaief, MD

(617) 726-1728meldaief@partners.org

More Information

Sponsor

Massachusetts General Hospital

Last update posted

Sep 29, 2025

Last verified

Sep, 2025

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Massachusetts General Hospital on 2025-09-29.