NCT07230990 · Subha Subramanian
Mechanisms Of Orbitofrontal Stimulation in Depression
(MOOD)
What this study is about
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.
View original scientific description
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.
Interventions
DEVICE
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.
DEVICE
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 measures
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.
The BDI-II is a 21-item self-report questionnaire assessing the severity of depressive symptoms over the past two weeks. Each item is rated from 0 to 3, reflecting increasing symptom severity. The total score range is 0 to 63 points, where higher scores indicate worse depressive symptoms. The investigators will examine the change in BDI-II scores in each experimental phase (randomized and open-label).
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.
The HDRS is a clinician-rated scale assessing the severity of depressive symptoms across mood, somatic, and cognitive domains. Items are scored on either 3- or 5-point scales depending on the symptom. The score ranges from 0 to 76, with higher scores reflecting greater severity.
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.
The RRS is a 22-item self-report questionnaire measuring the tendency to engage in repetitive, negative thinking about one's distress or mood. Each item is rated from 1 ("almost never") to 4 ("almost always"). Scores range from 22 to 88 points, with higher scores indicating greater rumination.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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
Where
- Boston, Massachusetts
Related conditions & keywords
Frequently asked questions
What is a clinical trial?
A clinical trial is a research study that tests new medical treatments, drugs, devices, or procedures to determine their safety and effectiveness. Trials are carefully designed and monitored to protect participants while advancing medical knowledge.
Is it safe to participate?
Clinical trials follow strict safety guidelines and ethical standards. Trials must be reviewed and approved, and participants are closely monitored by medical professionals throughout the study. You can withdraw at any time if you choose.
Will I be compensated?
Many clinical trials offer compensation for your time, travel expenses, and inconvenience. The specific compensation varies by study and will be discussed during the screening process. All study-related medical care is typically provided at no cost to participants.
Will I receive a placebo instead of treatment?
When effective treatment exists, participants typically receive either the standard treatment plus the study intervention, or the standard treatment plus placebo. You would not be denied effective care. Placebos are primarily used when no proven treatment is available, or in addition to standard care. Your trial consent form will clearly explain what treatments you may receive.
Can I leave a trial if I change my mind?
Absolutely. Participation in clinical trials is completely voluntary. You have the right to withdraw from the study at any time, for any reason, without penalty or loss of benefits to which you are otherwise entitled.
How long does a clinical trial last?
Trial duration varies widely depending on the study design and purpose. Some trials last just a few weeks, while others may continue for months or years. The study coordinator will provide specific timeline information during your screening call.
Data: ClinicalTrials.gov · synced May 14, 2026 · Source of record for eligibility and locations