ExAblate Transcranial MR Guided Focused Ultrasound for the Treatment of Essential Tremors

Study Overview
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Brief Summary
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The objective of this prospective, randomized, double-blind (to subjects, local site's blinded assessor and Tremor Core Lab assessors), crossover, multi-site, two-arm study (ExAblate treated arm Vs ExAblate Sham treated control arm) is to test the efficacy of treatment using the ExAblate Transcranial System and to further demonstrate safety in medication-refractory tremor in subjects with essential tremor (ET).

Detailed Description
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This study is evaluating a new technique for performing Thalamotomy for tremor control. While current techniques have possible invasive or radiation effects, the use of ExAblate if totally non-invasive and without any radiation. After informed consent and screening, eligible subjects will be randomized to either an ExAblate treatment or an ExAblate Sham or fake procedure. The chance of randomization to Sham is one out of four. Subjects who are randomized to Sham Control will undergo the same procedure and follow-up visits through their Month 3 visit. After the Month 3 assessments are complete, all subjects will be unblinded and those in the Sham treated group will have the option for an actual ExAblate treatment in an unblinded fashion, as long as they still qualify for ExAblate treatment. All subjects will be followed at 6 and 12 months and for up to 5 years as directed by their doctor.

Official Title
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A Pivotal Study to Evaluate the Effectiveness and Safety of ExAblate Transcranial MRgFUS Thalamotomy Treatment of Medication Refractory Essential Tremor Subjects

Conditions
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Essential Tremor

Intervention / Treatment
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* Device: Transcranial ExAblate
* Device: Sham Transcranial ExAblate


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Men and women, age 22 years and older Subjects who are able and willing to give informed consent and able to attend all study visits Subjects with a diagnosis of Essential Tremor as confirmed from clinical history and examination by a neurologist or neurosurgeon specialized in movement disorder Subject exhibits a significant disability from their ET despite medical treatment Subjects should be on a stable dose of all ET medications for 30 days prior to study entry Subject is able to communicate sensations during the ExAblate Transcranial procedure Exclusion Criteria: Subjects with unstable cardiac status Severe hypertension Subjects with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc. Known intolerance or allergies to the MRI contrast agent including advanced kidney disease or severely impaired renal function Significant claustrophobia that cannot be managed with mild medication Current medical condition resulting in abnormal bleeding and/or coagulopathy Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage History of intracranial hemorrhage History of multiple strokes, or a stroke within past 6 months Subjects who are not able or willing to tolerate the required prolonged stationary supine position during treatment Are participating or have participated in another clinical trial in the last 30 days Subjects unable to communicate with the investigator and staff Subjects with a history of seizures within the past year Subjects with brain tumors

Ages Eligible for Study
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Minimum Age: 22 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: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transcranial ExAblate<br>Transcranial ExAblate | Device: Transcranial ExAblate<br> <br> * Other names: Thalamotomy;|
| Sham Comparator: Sham Transcranial ExAblate<br>Sham Treatment with Transcranial ExAblate | Device: Sham Transcranial ExAblate<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Primary Efficacy Outcome | The treated upper limb CRST subscore (CRST A + B) applicable to upper limb in the ExAblate Group will be statistically better than the Sham control Group at Month 3 | Participants will be followed from the date of treatment until study completion, approximately up to 12 months | 
| Severity of Device and Procedure related complications | To evaluate the incidence and severity of adverse events (AEs) associated with the ExAblate Transcranial thalamotomy of medication-refractory Essential Tremor related to the ExAblate treatment | At the time of ExAblate Transcranial thalamotomy procedure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Clinical Rating Scale for Tremor Part C Score | Subject daily functionalities: as measured by CRST Part-C (subscales) Month 12 as compared to Baseline, and between treatment groups through Month 3 Durability (as measured by QUEST upper arm extremity questions) of the procedure as reflected by the efficacy data through change from baseline measures through Month 12 follow up Quality life claims: Questionnaire for Essential Tremor (QUEST) outcome (upper extremity questions) at Months 3 change from Baseline.as compared between treatment groups | Participants will be followed from the date of treatment until study completion, approximately up to 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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ExAblate Transcranial MRgFUS