Bilateral Essential Tremor Treatment With FUS

Study Overview
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Brief Summary
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Combined Phase II/III, multi-center, prospective, single-blinded trial. Ten (10) patients with who previously underwent successful and uncomplicated MRgFUS thalamotomy for essential tremor will undergo a contralateral treatment. The incidence of side effects will be determined at 1 and 3 months postoperatively, graded per the CTCAE v5 and analyzed by a data safety monitoring board. Upon successful review, this Phase II trial will be converted to a Phase III trial of utility that will enrol 40 additional patients. The primary outcome will be the change in QUEST score at 12 months postoperatively, as well as a patient-reported assessment of Health Utility. Secondary outcomes will include objective tremor, gait and speech assessments (filmed and scored by blinded evaluators), as well as quality of life questionnaires and adverse events questionnaires. Outcomes will be assessed immediately after the procedure, as well as 1, 3, 12, 24 and 36 months post-operatively.

Official Title
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Bilateral Essential Tremor Treatment With Magnetic Resonance-guided Focused Ultrasound

Conditions
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Essential Tremor

Intervention / Treatment
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* Procedure: Magnetic Resonance-guided Focused Ultrasound VIM Thalamotomy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Patients must be ≥ 18 years The patient has a primary diagnosis of ET or ET plus confirmed by a movement disorder neurologist; The patient previously underwent a MRgFUS (> 6 months ago); The tremor on the untreated side negatively impacts the patients' quality of life; The patient wants treatment of the contralateral side. Exclusion Criteria: Clinically relevant gait and/or balance impairment (e.g. wide-based, more than 2 falls/months, wheelchair, walker, cane use) Clinically relevant speech impairment (e.g. impairment of intelligibility) Inability to comply with the follow-up schedule; Refusal of the treating physician.

Ages Eligible for Study
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Minimum Age: 18 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: Treatment Group<br>Participants will undergo a thalamotomy contralateral to their previous treatment with MRgFUS using ExAblate Neuro 4000 device (InSightec Ltd, Tirat Carmel, Israel). | Procedure: Magnetic Resonance-guided Focused Ultrasound VIM Thalamotomy<br>* Ablation of contralateral VIM nucleus of thalamus with MRgFUS using ExAblate Neuro 4000 Device (InSightec Ltd, Tirat Carmel, Israel)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in QUEST Score | Difference in QUEST score between baseline and the 12-month follow-up, with statistical significance defined as p = 0.05 and a minimum clinically important difference (MCID) defined as 5 | 12 months | 
| Patient-based Assessment of Utility | A patient-reported assessment of utility after 12 months using the question Knowing what you know now, would you do this treatment again?. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Gait Assessment (NRS-11) | Patient-reported and blinded observer rating of the patient's ability to walk (Numerical rating scale (NRS-11) from 0 to 10, with 10 being best) | Immediately after surgery, post operative month 1, 3, 12, 24, 36 | 
| Gait Assessment (missteps) | Number of missteps in a 6 m standardized tandem walk | Immediately after surgery, post operative month 1, 3, 12, 24, 36 | 
| Falls | Number of falls in last month | Post operative month 1, 3, 12, 24, 36 | 
| Speech Assessment (NRS-11) | Patient-reported and blinded observer rating of the patient's ability to speak (Numerical rating scale (NRS-11) from 0 to 10, with 10 being best) | Immediately after surgery, post operative month 1, 3, 12, 24, 36 | 
| Numbness | Incidence of new-onset numbness | Immediately after surgery, post operative month 1, 3, 12, 24, 36 | 
| Dysgeusia | Incidence of taste alterations | Immediately after surgery, post operative month 1, 3, 12, 24, 36 | 
| Other adverse events | Incidence of other adverse events as classified in the CTCAE | Immediately after surgery, post operative month 1, 3, 12, 24, 36 | 
| Tremor (CRST) | Assessment of tremor using the Clinical Rating Scale for Tremor (CRST) parts A (0-88) and B (0-36), higher scores correspond to a worse tremor). | Immediately after surgery, post operative month 1, 3, 12, 24, 36 | 
| Quality of life (QUEST) | QUality of life in ESsential Tremor (QUEST) questionnaire (0-100%, higher scores correspond to a worse quality of life) | Post operative month 1, 3, 12, 24, 36 | 
| Quality of life (CRST part C) | Part C of the Clinical Rating Scale for Tremor (CRST) (0-32, higher scores correspond to a worse quality of life) | Post operative month 1, 3, 12, 24, 36 | 
| Health Utility (EQ-5D-5L) | Health Utility measured using the EQ-5D-5L and computed using the Canadian preference weights. Values range from 0 to 1, with 1 representing a perfect health. | Post operative month 1, 3, 12, 24, 36 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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High-Intensity Focused Ultrasound Ablation