Recruiting

TMS

Sponsor:

Subha Subramanian

Code:

NCT07230990

Conditions

Major Depressive Disorder (MDD)

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Interventions

Sham TMS

Active TMS

Study Details

Brief summary:

The orbitofrontal cortex (OFC), a region involved in emotional regulation, decision making, and reward processing, is a key area linked to antidepressant response. This study tests whether noninvasive stimulation of the OFC using transcranial magnetic stimulation (TMS) can improve depressive symptoms. TMS uses magnetic fields generated by a coil placed next to the scalp to alter brain activity.

Conditions

Major Depressive Disorder (MDD)

Study ID

NCT07230990

Start date

Apr 15, 2026

Status verified date

Apr, 2026

Completion date

Dec, 2030

Anticipated

Primary completion date

Dec, 2030

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 18 - 65

Healthy Volunteers: Not accepted

Inclusion Criteria:

  • Age 18-65 years
  • Must be able to read, speak and understand English
  • DSM-5 diagnosis of major depressive disorder, experiencing a moderate to severe depressive episode (Hamilton Depression Rating Scale score greater than or equal to 17 points)
  • Must be judged by study staff to be capable of completing the study procedures
  • Participants will be in stable outpatient treatment with no recent (within the past 30 days) hospitalizations or changes in their medication regimens

Exclusion Criteria:

  • DSM-5 moderate to severe substance use disorder within the past three months, based on Structured Clinical Interview for DSM-5
  • Conditions that might result in increased risks of side effects or complications from rTMS or MRI, including:

  • History of fainting spells of unknown or undetermined etiology that might constitute seizures
  • Diagnosis of epilepsy with the exception of a single seizure of benign etiology (e.g., febrile seizures) in the judgment of a board-certified neurologist
  • Current or past history of a neurological disorder, such as stroke, a progressive neurologic disease, or intracranial brain lesion(s); and history of previous neurosurgery or head trauma that resulted in residual neurologic impairment
  • Any unstable medical condition
  • Any metal in the brain or skull (excluding dental fillings) unless cleared by the responsible covering MD
  • Any devices which could be affected by TMS or MRI such as a pacemaker, medication pump, nerve stimulator, cochlear implant, TENS unit, ventriculo-peritoneal shunt unless cleared by the responsible covering MD
  • Pregnancy; All female participants will be required to have a pregnancy test; any participant who is pregnant will not be enrolled in the study. The pregnancy test will be administered by study staff trained to administer point of care pregnancy testing that complies with institutional laboratory policies

Study Design

Enrollment

80 participants

Anticipated

Allocation

Randomized

Intervention Model

Crossover

Primary purpose

Treatment

Interventions and Outcome Measures

Arms

active comparator: Active OFC stimulation

Continuous intermittent theta burst stimulation (cTBS, a type of inhibitory TMS) to the right OFC.

sham comparator: Sham OFC stimulation

Sham TMS treatment to the right OFC

Interventions

Sham TMS

The MagVenture MagPro system's active/sham coil (e.g., Cool-B65 A/P) will be used to deliver either active or sham TMS. The sham mode reproduces the same clicking sound and scalp sensation as active stimulation but does not induce cortical activation. The built-in MagPro double-blind feature ensures operator, participant, and investigator blinding. All participants will be randomized to receive active or sham TMS to the OFC in the first phase.

Active TMS

TMS uses magnetic fields generated by a coil placed next to the scalp to alter brain activity at a specific region (i.e., OFC) protocol. Here, active TMS protocol is continuous intermittent theta burst stimulation (cTBS, a type of inhibitory TMS) to the right OFC. Investigators will use the MagVenture MagPro system's active/sham coil (e.g., Cool-B65 A/P) to deliver either active or sham TMS. All participants will be randomized to receive active or sham TMS to the OFC in the first phase. In the second phase, all participants will receive active TMS to the OFC. The active protocol to the right OFC is: continuous intermittent theta burst stimulation (cTBS, a type of inhibitory TMS).

Primary outcome measure

  • Beck Depression Inventory II (BDI-II) [ Time Frame: The survey will be administered at 4 timepoints: Day 1 (baseline) and Day 10 (last day) of randomized phase; Day 1 (baseline) and Day 10 (last day) of open-label phase. ]
  • Hamilton Depression Rating Scale (HDRS) - 24 item version [ Time Frame: The survey will be administered at 4 timepoints: Day 1 (baseline) and Day 10 (last day) of randomized phase; Day 1 (baseline) and Day 10 (last day) of open-label phase. ]
  • Rumination Response Scale (RRS) [ Time Frame: The survey will be administered at 4 timepoints: Day 1 (baseline) and Day 10 (last day) of randomized phase; Day 1 (baseline) and Day 10 (last day) of open-label phase. ]

Central Contacts and Locations

Central contacts

Subha Subramanian, MD

6176675247ssubram5@bidmc.harvard.edu

Locations

Beth Israel Deaconess Medical Center

Recruiting

Boston, Massachusetts, United States, 02215

Contacts

Subha Subramanian, MD

ssubram5@bidmc.harvard.edu

More Information

Sponsor

Subha Subramanian

Last update posted

May 14, 2026

Last verified

Apr, 2026

Keywords

  • Depression
  • Transcranial magnetic stimulation (TMS)
  • orbitofrontal cortex
  • Frontal pole

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by Subha Subramanian on 2026-05-14.