Personalized Ultrasonic Brain Stimulation for Depression

Study Overview
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Brief Summary
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This study will evaluate a new form of non-invasive brain stimulation for individuals with depression. Personalized low-intensity transcranial focused ultrasound stimulation will first be delivered using a range of stimulation parameters during psychological and physiological monitoring. A well-tolerated stimulation protocol will then be selected for subsequent testing in a blinded randomized sham-controlled cross-over trial to evaluate brain target engagement using magnetic resonance imaging.

Official Title
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Personalized Ultrasonic Brain Stimulation for Depression: A Pilot Study of Target Engagement and Mood Effects

Conditions
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Major Depressive Episode

Intervention / Treatment
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* Device: Diadem prototype


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65, any gender Primary diagnosis of major depressive disorder or bipolar disorder Current moderate-to-severe depressive episode, without psychotic features, lasting at least 2 months Self-rated 16-item Quick Inventory of Depressive Symptomatology (QIDS) total score > 10 Stated willingness to comply with all study procedures and avoid changes to psychiatric treatments (medications, psychotherapy) for the duration of the study For females of reproductive potential: negative pregnancy test or use of highly effective contraception for at least 1 month prior to baseline; agreement to use such a method throughout the study Capacity to provide informed consent; provision of a signed and dated consent form Exclusion Criteria: History of serious brain injury or other neurologic disorder Poorly managed general medical condition Pregnant or breast feeding Implanted device in the head or neck MRI intolerance or contraindication Brain stimulation (e.g., ECT, TMS, VNS) in the past month Suicidal ideation (Columbia Suicide Severity Rating Scale screen item #2, past month) Lifetime history of a serious suicide attempt Moderate-to-severe substance use disorder (past 3 months) Obsessive compulsive disorder (past month) Posttraumatic stress disorder (past month) Schizophrenia-spectrum disorder (lifetime) Neurocognitive disorder (past year) Personality disorder as a current focus of treatment Clinically inappropriate for participation in the study as determined by the study team

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active stimulation<br>Personalized low-intensity transcranial focused ultrasound stimulation of deep brain target (subgenual cingulate or alternative targets) | Device: Diadem prototype<br>* Diadem prototype device delivers personalized low-intensity transcranial focused ultrasound stimulation<br>|
| Sham Comparator: Sham stimulation<br>Personalized low-intensity transcranial focused ultrasound stimulation of lateral ventricle | Device: Diadem prototype<br>* Diadem prototype device delivers personalized low-intensity transcranial focused ultrasound stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target engagement: MRI quantification of brain activation | Blood oxygenation level dependent (BOLD) or arterial spin labeling (ASL) response to active versus sham stimulation | 1 day at MRI study visit | 
| Target engagement: MRI quantification of brain connectivity | Resting functional connectivity of target in response to active versus sham stimulation | 1 day at MRI study visit | 
| Mood effects: momentary mood change | 4-item Affect Change Scale: valence, arousal, depression, anxiety | 1 day at stimulation study visit | 
| Mood effects: subjective mood state | Positive and Negative Affect Schedule Extended (PANAS-X) | 1 day at stimulation study visit |