Open Label Study for the Use of Transcranial Ultrasound Treatment of Tremor

Study Overview
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Brief Summary
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The purpose of this Phase I open label study is to evaluate longer term tolerability and potential effectiveness of transcranial ultrasound in people with tremor as a results of Parkinson's Disease or Essential Tremor.

Detailed Description
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This study is designed to evaluate the safety and efficacy of focused ultrasound in patients with Parkinson's Disease or Essential Tremor characterized by tremor. The safety of this protocol will be closely monitored and data will be used to determine whether any significant safety issues exist when using focused ultrasound. Adverse events will be noted whenever they occur but will be recorded at the time of the procedure and throughout routine follow-ups, which will persist weekly throughout the duration of the active study protocol. Patients deemed potentially appropriate candidates for focused ultrasound therapy will be treated with 8 sessions of transcranial ultrasound, each of which consists of 10 to 30 minutes of active administration. Clinical and safety outcome measures will be obtained throughout and after completion of the study protocol.

Official Title
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Open Label Study for the Use of Transcranial Ultrasound Treatment of Tremor

Conditions
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Tremor, Parkinson Disease, Essential Tremor

Intervention / Treatment
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* Device: Focused Ultrasound


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: In order for a subject to be considered for the Essential Tremor application of this study, the following criteria are required: Subjective complaint of tremor assessed and validated by physician Must be willing to comply with the study protocol English Proficiency At least 18 years of age At most 90 years of age In order for a subject to be considered for the Parkinson's Disease application of this study, the following criteria are required: Diagnosis of Parkinson's Disease validated by physician Must be willing to comply with the study protocol English Proficiency At least 18 years of age At most 90 years of age Exclusion Criteria: In order for a subject to be considered for this study, he/she may NOT have any of the following: Subjects not English proficient Subjects unable to give informed consent Subjects do not meet age requirements (18-90) Subjects who would not be able to lay down without excessive movement in a calm environment sufficiently long enough to be able to achieve sleep Pregnancy, women who may become pregnant or are breastfeeding Women with child-bearing potential who are not willing to use a double-barrier birth control method Males not willing to use a double-barrier birth control method with female sex partners with child-bearing potential Advanced terminal illness Any active cancer or chemotherapy Any other neoplastic illness or illness characterized by neovascularity Macular degeneration 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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No

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: Experimental<br>Participants will undergo ten to thirty minutes of transcranial ultrasound treatment. The sanitation device will be aimed at the hypothalamus. 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 middle cerebral artery, and optical tracking technology (e.g., AntNeuro Visor2™ system) may be used in tandem with the Brainsonix 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 |
| --- | --- | --- |
| Essential Tremor Rating Assessment Scale (TETRAS) | The Essential Tremor Rating Assessment Scale was developed by the Tremor Research Group to quantify essential tremor severity and its impact on activities of daily living. The ADL section of TETRAS has 12 items, each rated 0, 1, 2, 3 or 4. The maximum total score is 48. Item 1 addresses speech; item 10 addresses occupational impairment; and item 12 assesses social impact. The other 9 items assess activities that are affected primarily by upperweighting of lower limb tremor in the total performance score. | Baseline | 
| Essential Tremor Rating Assessment Scale (TETRAS) | The Essential Tremor Rating Assessment Scale was developed by the Tremor Research Group to quantify essential tremor severity and its impact on activities of daily living. The ADL section of TETRAS has 12 items, each rated 0, 1, 2, 3 or 4. The maximum total score is 48. Item 1 addresses speech; item 10 addresses occupational impairment; and item 12 assesses social impact. The other 9 items assess activities that are affected primarily by upperweighting of lower limb tremor in the total performance score. | Through Completion of Study (Average time 8-weeks) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 9 Hole Pegboard Task (9 HPT) | A validated assessment for fine motor skills, the 9-HPT involves having a participant move 9 pegs individually from starting position to 9 separate peg-holes, as quickly as possible, and to immediately return the 9 pegs to the starting position upon filling the final peg-hole. This is performed separately for each hand. The score is the time (seconds/milliseconds) that it takes to complete the task, recorded separately for dominant and non-dominant hands. The minimum detectable change is 2.6 seconds for the dominant hand and 1.3 seconds for the non-dominant hand. | Baseline | 
| 9 Hole Pegboard Task (9 HPT) | A validated assessment for fine motor skills, the 9-HPT involves having a participant move 9 pegs individually from starting position to 9 separate peg-holes, as quickly as possible, and to immediately return the 9 pegs to the starting position upon filling the final peg-hole. This is performed separately for each hand. The score is the time (seconds/milliseconds) that it takes to complete the task, recorded separately for dominant and non-dominant hands. The minimum detectable change is 2.6 seconds for the dominant hand and 1.3 seconds for the non-dominant hand. | Through Completion of Study (Average time 8-weeks) | 
| Parkinson's Activities of Daily Living Scale (PAD-L) | The Parkinson's Activities of Daily Living Scale is a self-report activities of daily living scale designed to assess difficulties in daily activities due to symptoms of Parkinson's Disease. | Baseline | 
| Parkinson's Activities of Daily Living Scale (PAD-L) | The Parkinson's Activities of Daily Living Scale is a self-report activities of daily living scale designed to assess difficulties in daily activities due to symptoms of Parkinson's Disease. | Through Completion of Study (Average time 8-weeks) |