Deep Brain Therapy With Low-intensity Ultrasound for Generalized Chronic Pain

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 generalized chronic pain. 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 CVAS and PROMIS numerical rating scales of pain.

Official Title
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Deep Brain Therapy With Low-intensity Ultrasound for Generalized Chronic Pain: A Pilot Study of Target Engagement and Analgesic Effects

Conditions
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Chronic Pain, Chronic Pain Syndrome, Widespread Chronic Pain

Intervention / Treatment
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* Device: Verum stimulation with Diadem prototype
* Device: Sham stimulation with Diadem prototype


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age 18-65, any gender Primary diagnosis of generalized chronic pain or widespread chronic pain. Moderate-to-severe chronic pain lasting at least 2 months Stated willingness to comply with all study procedures and avoid changes to current treatments (medications, physical therapy, cognitive behavioral therapy) 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., VNS, TMS) in the past month Lifetime history of a serious suicide attempt (Hooley et al., 2014) 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>Low-intensity transcranial focused ultrasound stimulation of deep brain targets involved in pain perception Intervention: Device: Diadem prototype | Device: Verum stimulation with Diadem prototype<br>* Diadem prototype device delivers focused low-intensity ultrasound stimulation<br>|
| Sham Comparator: Sham stimulation<br>Low-intensity transcranial focused ultrasound stimulation using unfocused wave Intervention: Device: Diadem prototype | Device: Sham stimulation with Diadem prototype<br>* Diadem prototype device delivers active sham, unfocused low-intensity ultrasound stimulation<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Target engagement: brain activation | MRI quantification of blood oxygenation level dependent (BOLD) activation. | 1 day At MRI study visit | 
| Target engagement: brain connectivity | Pearson's correlation of BOLD signals between the stimulated target and connected regions. | 1 day At MRI study visit | 
| Pain intensity: momentary change | Computerized Visual Analogue Scale. The scale is measured using a continuous slider. At its left boundary, the slider indicates no pain (score 0). At its right boundary, the slider indicates worst pain imaginable (score 100). A lower score indicates a better treatment outcome. | 1 day At stimulation visit | 
| Pain intensity: subjective state | PROMIS scale of pain intensity. Scores range from 1 (no pain) to 5 (severe pain). A lower score indicates a better treatment outcome. | 1 day At stimulation visit | 
| Depression scale: subjective state | PROMIS scale of depression. Scores range from 1 (not at all depressed) to 5 (severely depressed). A lower score indicates a better treatment outcome. | 1 day At stimulation visit | 
| Anxiety scale: subjective state | PROMIS scale of anxiety. Scores range from 1 (not at all anxious) to 5 (severely anxious). A lower score indicates a better treatment outcome. | 1 day At stimulation visit |