Ultrasonic Neuromodulation for Treatment of PTSD

Study Overview
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Brief Summary
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This study will evaluate a new form of non-invasive deep brain therapy for individuals with post-traumatic stress disorder (PTSD). Low-intensity transcranial focused ultrasound stimulation will first be delivered using a range of stimulation parameters during psychophysical and physiological monitoring. A well-tolerated stimulation protocol will be selected for subsequent testing in a blinded randomized sham-controlled cross-over trial. The trial will evaluate brain target engagement using magnetic resonance imaging and numerical scales of PTSD, cognitive performance, and mood.

Official Title
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Deep Brain Therapy With Low-intensity Ultrasound for Treatment of Post-traumatic Stress Disorder

Conditions
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PTSD

Intervention / Treatment
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* Device: Diadem


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Positive PTSD diagnosis; PCL-5 > 20 Exclusion Criteria: Inability to complete MRI Suicidal ideation

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>Low-intensity transcranial focused ultrasound stimulation of deep brain targets affected by PTSD. | Device: Diadem<br>* The device delivers low-intensity ultrasonic waves into specified brain targets.<br>|
| Sham Comparator: Sham stimulation<br>Sham stimulation that applies the device in the same way as verum but only delivers auditory sounds correspoding to the ultrasonic pulses. | Device: Diadem<br>* The device delivers low-intensity ultrasonic waves into specified brain targets.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| PTSD Checklist for DSM-5 (PCL-5) | 20-item self-report measure that assesses the 20 DSM-5 symptoms of PTSD. The total severity scores range from 0 to 80. | Up to 3 months following study initiation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| National Institutes of Health Toolbox Cognitive Battery (NIHTB-CB) | The NIHTB-CB provides the following summary scores: Total Cognition Composite, Fluid Composite (includes Dimensional Change Card Sort, Flanker Inhibitory Control and Attention, Picture Sequence Memory (Form A), List Sorting Working Memory, and Pattern Comparison tests), and Crystallized Composite (includes Picture Vocabulary and Oral Reading Recognition tests). The scores are normalized to have a mean score of 10 and standard deviation of 3. | Up to 3 months following study initiation | 
| California Verbal Learning Test, 3rd Edition (CVLT3) | A verbal learning and memory test designed to test immediate recall, short delay recall, long delay recall, and recognition memory, as well as the memory strategies being used by the participant. The Brief Form of the CVLT 3 consists of nine words, administered repeatedly over 4 immediate recall trials. The scoring software provides normative data. | Up to 3 months following study initiation | 
| PROMIS scale of Pain Intensity | The score assess the worst, average, and current levels of pain on a scale from 1 (no pain) to 5 (very severe) | Up to 3 months following study initiation | 
| Hamilton Depression Rating Scale (HDRS-17) | This 17-item questionnaire rates the severity of depression by probing mood, feelings of guilt, suicide ideation, insomnia, agitation or retardation, anxiety, weight loss, and somatic symptoms. The scores range from 0 (no symptoms) to 52 (worst possible). | Up to 3 months following study initiation | 
| Pittsburgh Sleep Quality Index (PSQI) | Test consisting of 7 components summed to yield a global PSQI score, ranging from of 0 (good sleep) to 21 (poor sleep). | Up to 3 months following study initiation |