Bilateral Essential Tremor Treatment With FUS (BEST-FUS)

Bilateral Essential Tremor Treatment With Magnetic Resonance-guided Focused Ultrasound

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.

Study Overview

• Status: Recruiting
• Conditions: Essential Tremor
• Intervention / Treatment: Procedure: Magnetic Resonance-guided Focused Ultrasound VIM Thalamotomy

• Study Type: Interventional
• Enrollment (Anticipated): 50
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Christian Iorio-Morin, MD, PhD; Email: christian.iorio-morin@usherbrooke.ca
• Study Contact Backup: Name: Martha Lenis, BHA; Phone Number: 2797 +14166035800; Email: martha.lenis@uhnresearch.ca

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M5T 2S8
      • Recruiting
      • Toronto Western Hospital, University Health Network
      • Contact: Martha Lenis, BHA; Phone Number: 2797 +14166035800; Email: martha.lenis@uhnresearch.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Treatment Group; 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; Ablation of contralateral VIM nucleus of thalamus with MRgFUS using ExAblate Neuro 4000 Device (InSightec Ltd, Tirat Carmel, Israel)

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University Health Network, Toronto
• Collaborators: Université de Sherbrooke
• Investigators: Principal Investigator: Andres Lozano, MD, PhD, University of Toronto

Study record dates

Study Major Dates

• Study Start (Actual): July 8, 2020
• Primary Completion (Anticipated): October 1, 2024
• Study Completion (Anticipated): October 1, 2024

Study Registration Dates

• First Submitted: July 29, 2020
• First Submitted That Met QC Criteria: August 3, 2020
• First Posted (Actual): August 6, 2020

Study Record Updates

• Last Update Posted (Actual): May 17, 2022
• Last Update Submitted That Met QC Criteria: May 16, 2022
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: High-Intensity Focused Ultrasound Ablation
• Additional Relevant MeSH Terms: Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Movement Disorders; Dyskinesias; Tremor; Essential Tremor
• Other Study ID Numbers: 20-5172

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No