Focused Ultrasound for the Treatment of Neuropathic Pain

Study Overview
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Brief Summary
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A possible treatment approach for neuropathic pain would employ a process designed to promote healthier function of the ventral posteromedial (VPM) and ventral posterolateral (VPL) thalamic nuclei. This study is designed to employ focused ultrasound technology to target the VPM and VPL thalamus among participants with ongoing neuropathic pain syndromes to evaluate for tolerability and early efficacy.

Detailed Description
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The present open-label study is being undertaken to evaluate focused transcranial ultrasound therapy as an intervention for patients with neuropathic pain. The subjects in this research study will be recruited through medical practice. Participants who are enrolled will undergo 8 consecutive weekly ultrasound sessions. Targeting for treatment will be based on patient MRI scans using stereotaxic techniques.

Official Title
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Open Label Study for the Use of Focused Transcranial Ultrasound for Treatment of Neuropathic Pain

Conditions
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Neuropathic Pain

Intervention / Treatment
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* Device: Focused Ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: History of neuropathic pain (onset, location, intensity, duration, quality, aggravating factors) Confirmation of nervous system injury through imaging or negative or positive sensory signs confined to the corresponding bodily area Failure from at least 3 pharmacological treatments (e.g., antidepressants, anticonvulsants, opioids) At least 18 years of age Exclusion Criteria: Subjects unable to give informed consent Subjects who would not be able to lay down without excessive movement in a calm environment Pregnancy, women who may become pregnant or are breastfeeding Subjects with scalp rash or open wounds on the scalp (for example from treatment of squamous cell cancer)

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Active<br>Patients will undergo ten to thirty minutes of transcranial ultrasound treatment. The sonification device will be aimed at the thalamus. Targeting will include reference to scalp fiducials based on the obtained MRI; confirmation of target accuracy will either be obtained by Doppler waveform confirmation or optical tracking technology which co-registers patient neuroimaging with real space. | Device: Focused Ultrasound<br>* The DWL Doppler ultrasound device enables visual and auditory waveform confirmation of the anterior cerebral artery, and optical tracking technology (e.g., AntNeuro Visor2™ system) may be used in tandem with the Brainsonix Pulsar 1002 ultrasound device to track a patient's brain in virtual space as well as their physical location, thereby ensuring accurate placement.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief Pain Inventory (BPI) | Self-report measure containing a composite pain score and functional interference score. The pain subscale contains 4 questions, each with answers ranging from 0 'no pain' to 10 'pain as bad as you can imagine.' Total possible score for the pain subscale is 40 points. The functional/interference subscale contains 7 questions, with each answer ranging from 0 'does not interfere' to 10 'completely interferes.' The maximum possible score for the interference subscale is 70 points. The total overall composite BPI score is out of 100 maximum points. A clinical improvement is considered a decrease in BPI overall composite score by at least 30% from baseline. | Baseline | 
| Numeric Pain Rating Scale (NPRS) | The NRPS is a unidimensional measure of pain intensity for adults. The 11-point numeric scale ranges from '0' representing 'no pain' to 10 representing 'worst possible pain.' The NPRS can be administered verbally or graphically for self-completion. The respondent is asked to indicate the numeric scale value that best describes the intensity of their pain within the last 24-hours. Clinical improvement is denoted by at least 3 points improvement. | Baseline | 
| Patient Health Questionnaire (PHQ-9) | The PHQ-9 is a 9-item, self-report questionnaire to evaluate for depressive symptoms. Each question asks the patient if they have experienced a particular depressive symptom over the past two weeks. Answers may range from 0 (not at all), 1 (several days/week), 2 (more than half of the days), and 3 (nearly every day). Maximum total score is 27 points. A higher score indicates more severe depressive symptoms. A reduction in total score by at least 30% is considered clinically meaningful. | Baseline | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Brief Pain Inventory (BPI) | Self-report measure containing a composite pain score and functional interference score. The pain subscale contains 4 questions, each with answers ranging from 0 'no pain' to 10 'pain as bad as you can imagine.' Total possible score for the pain subscale is 40 points. The functional/interference subscale contains 7 questions, with each answer ranging from 0 'does not interfere' to 10 'completely interferes.' The maximum possible score for the interference subscale is 70 points. The total overall composite BPI score is out of 100 maximum points. A clinical improvement is considered a decrease in BPI overall composite score by at least 30% from baseline. | Post Final Treatment (8 weeks from baseline) | 
| Numeric Pain Rating Scale (NPRS) | The NRPS is a unidimensional measure of pain intensity for adults. The 11-point numeric scale ranges from '0' representing 'no pain' to 10 representing 'worst possible pain.' The NPRS can be administered verbally or graphically for self-completion. The respondent is asked to indicate the numeric scale value that best describes the intensity of their pain within the last 24-hours. Clinical improvement is denoted by at least 3 points improvement. | Post Final Treatment (8 weeks from baseline) | 
| Patient Health Questionnaire (PHQ-9) | The PHQ-9 is a 9-item, self-report questionnaire to evaluate for depressive symptoms. Each question asks the patient if they have experienced a particular depressive symptom over the past two weeks. Answers may range from 0 (not at all), 1 (several days/week), 2 (more than half of the days), and 3 (nearly every day). Maximum total score is 27 points. A higher score indicates more severe depressive symptoms. A reduction in total score by at least 30% is considered clinically meaningful. | Post Final Treatment (8 weeks from baseline) |