NCT07230990

Mechanisms Of Orbitofrontal Stimulation in Depression

Mechanisms Of Orbitofrontal Stimulation in Depression (MOOD)

• Status: Not Yet Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 80 (estimated)
• Sponsor: Subha Subramanian · Academic / Other
• Sex: All
• Age: 18 Years – 65 Years
• Healthy volunteers: Not accepted

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.

Detailed description

The main purpose of this study is to test a new treatment target for major depressive disorder (MDD) and to understand the brain mechanisms that may lead to antidepressant response. The treatment target of this study is the right orbitofrontal cortex (OFC), a brain region towards the front of the brain involved in emotion regulation, reward-processing, and decision-making. Other studies have shown that stimulating the OFC can improve depression symptoms. However, no study has yet directly compared the effects of real (active) versus placebo (sham) OFC stimulation on both mood and brain function. Comparison of active versus sham treatment is key in medical research. This study aims to fill that gap by comparing active versus sham stimulation of the right OFC in people with MDD who are currently experiencing moderate to severe symptoms. Participants will take part in a two phases: a triple-blind, randomized, sham-controlled phase, followed by an open-label phase where all participants receive active OFC stimulation. Aim 1: To determine whether active TMS targeting the right OFC, compared to sham stimulation at the same site, reduces depressive symptom severity in individuals with MDD. Aim 2: To test whether active TMS to the right OFC, compared to sham stimulation at the same site, reduces ruminative symptoms in individuals with MDD.

Conditions

• Major Depressive Disorder (MDD)

Interventions

Type	Name	Description
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).

Timeline

• Start date: 2026-01-01
• Primary completion: 2030-12-01
• Completion: 2030-12-01
• First posted: 2025-11-17
• Last updated: 2025-11-17

Regulatory

• FDA-regulated device study