MR-Guided Focused Ultrasound (MRgFUS) for the Management of Tremor in Patients With Multiple Sclerosis (MSFUS001)

A Feasibility and Safety Clinical Trial of the Magnetic Resonance Guided Focused Ultrasound (MRgFUS) for the Management of Tremor in Patients With Multiple Sclerosis

This study will be a single-centre, prospective, single-arm, open-label pilot trial assessing the feasibility and safety of unilateral MR-guided focused ultrasound (MRgFUS) thalamotomy for refractory hand tremor in up to 12 patients with multiple sclerosis (relapsing-remitting, primary progressive or secondary progressive MS). This study will be conducted at the Focused Ultrasound Centre of Excellence and MS Clinic located at Sunnybrook Health Sciences Centre/ University of Toronto. Patients with stable MS and refractory hand tremor providing informed consent will receive MRgFUS thermal ablation of the Vim thalamus contralateral to the most affected side of the body (frequently this will be the dominant hand).

Study Overview

• Status: Unknown
• Conditions: Multiple Sclerosis
• Intervention / Treatment: Device: Focused Ultrasound (MRgFUS) for the Management of Tremor in Patients With Multiple Sclerosis

• Study Type: Interventional
• Enrollment (Anticipated): 6
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Ontario
    • Toronto, Ontario, Canada, M4N 3M5
      • Recruiting
      • Sunnybrook Health Sciences Centre
      • Contact: Nadia Scatlebury, PhD; Phone Number: 4390 +1 416-480-6100; Email: nadia.scantlebury@sunnybrook.ca

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 78 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or Female aged 18-80 years
• Willing and able to give consent and attend all study visits
• A confirmed diagnosis of medication-refractory, MS-related hand tremor
• No clinical evidence of relapse over 12 months or more before enrollment
• No MRI activity over 3 months or more before enrollment
• Presence of disabling postural or kinetic tremor
• Unsatisfactory tremor response to adequate trials of at least two medications
• Able to communicate sensations during the treatment
• Stable doses of all medications for 30 days prior to and during study

Exclusion Criteria:

• Severe cerebellar dysfunction measured by Scale for the Assessment and Rating of Ataxia (>35 out of 40)
• Severe weakness or sensory loss in arm contralateral to the side of the brain considered for MRgFUS
• Evidence of a superimposed or atypical movement disorder
• Unstable cardiac status such as angina pectoris, congestive heart failure, etc.
• Severe hypertension
• Patients with standard contraindications for MR imaging
• History of abnormal bleeding and/or coagulopathy
• Ischemic or hemorrhagic stroke within 6 months
• Symptoms and signs of increased intracranial pressure (e.g. headache, nausea, vomiting, lethargy, and papilledema)
• Untreated, uncontrolled sleep apnea
• Active or suspected acute or chronic uncontrolled infection
• Receiving anticoagulant or antiplatelet therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage within one month of MRgFUS surgery
• Not able or willing to tolerate the required prolonged stationary supine position during treatment
• Participating or have participated in another clinical trial in the last 30 days
• Unable to communicate with the investigator and staff
• Presence of neurodegenerative disease or significant cognitive impairment
• Presence of significant cognitive impairment (≤24 on MMSE)
• Uncontrolled major psychiatric disorder or suicidal ideation
• Risk factors for intraoperative or postoperative bleeding or documented coagulopathy
• Presence of brain tumours
• Any illness that in the investigator's opinion preclude participation in this study
• Pregnancy or lactation
• Legal incapacity or limited legal capacity
• Deep Brain Stimulation or a prior stereotactic ablation of the basal ganglia
• A history of seizures within the past year

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Device Feasibility
• 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: Patients with Multiple Sclerosis and Tremor; Participants will undergo MRgFUS thermal ablation of the ventral intermedius (Vim) thalamus contralateral to the most affected side of the body.	Device: Focused Ultrasound (MRgFUS) for the Management of Tremor in Patients With Multiple Sclerosis; The intervention is MRIgFUS thermal ablation of the ventral intermedius (Vim) thalamus contralateral to the most affected side of the body.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Composite safety outcome of MRgFUS thalamotomy	Composite outcome of detectable Vim lesion on MRI scan; AND lack of new-onset or worsening of contralateral upper limb sensory loss or weakness	90 days

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence and severity of adverse events related to MRgFUS thalamotomy	Incidence and severity of adverse events possibly, probably or definitely related to the MRgFUS procedure at 1, 7, 30, 90 and 120 days after treatment.	1, 7, 30, 90 and 120 days
Incidence and severity of adverse events related to MS disease relapse or progression	Incidence and severity of AEs possibly, probably or definitely-related to MS disease relapse or progression (based on clinical assessment) over 30 and 90 days.	30 and 90 days
Changes from baseline in the EDSS (Expanded Disability Status Scale) scores	Changes from baseline in the EDSS scores at 30 and 90 days. This is a scale to of quantify disability in multiple sclerosis. Score: 0 to 10 with higher scores meaning worse outcome.	30 and 90 days
Changes from baseline in the SARA (Scale for Assessment and Rating of Ataxia) scores	Changes from baseline in the SARA scores at 30 and 90 days. This is a scale to of quantify function and disability related to ataxia. Score: 0 to 40 with higher scores meaning worse outcome.	30 and 90 days
Changes from baseline in the speech intelligibility (percentage of intelligible words recorded during standardized passage reading)	Changes from baseline in intelligibility percentage at 30 and 90 days. Score: 0 to 100% with higher scores meaning better outcome.	30 and 90 days
Changes from baseline in QUEST (Quality of Life in Essential Tremor Questionnaire) scores	Changes from baseline in QUEST scores at 30 and 90 days. This is a 30-item scale developed specifically for patients with essential tremor to measure items impacting perceived quality of life (QOL) that generic QOL measures do not effectively capture, including activities of daily living that are affected by tremor. Higher scores mean worse outcome.	30 and 90 days
Change from baseline in the CRST (Clinical Rating Scale for Tremors)	Change from baseline in the treated upper limb tremor subscore of the CRST at 30 and 90 days. Score: 0 to 32 with higher scores meaning worse outcome.	30 and 90 days
Composite safety outcome of MRgFUS thalamotomy	Composite outcome of detectable Vim lesion on MRI scan; AND lack of new-onset or worsening of contralateral upper limb sensory loss or weakness	30 days

Collaborators and Investigators

• Sponsor: Sunnybrook Health Sciences Centre
• Collaborators: Multiple Sclerosis Society of Canada
• Investigators: Principal Investigator: Agessandro Abrahao, MD, MSc, Sunnybrook Health Sciences Centre; Principal Investigator: Nir Lipsman, MD, PhD, Sunnybrook Health Sciences Centre

Study record dates

Study Major Dates

• Study Start (Actual): January 16, 2020
• Primary Completion (Anticipated): March 1, 2021
• Study Completion (Anticipated): July 1, 2021

Study Registration Dates

• First Submitted: January 31, 2020
• First Submitted That Met QC Criteria: February 19, 2020
• First Posted (Actual): February 21, 2020

Study Record Updates

• Last Update Posted (Actual): February 21, 2020
• Last Update Submitted That Met QC Criteria: February 19, 2020
• Last Verified: February 1, 2020

More Information

Terms related to this study

• Keywords: Multiple Sclerosis; Tremor; MR-guided Focused Ultrasound
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Immune System Diseases; Demyelinating Autoimmune Diseases, CNS; Autoimmune Diseases of the Nervous System; Demyelinating Diseases; Autoimmune Diseases; Neurologic Manifestations; Dyskinesias; Multiple Sclerosis; Sclerosis; Tremor
• Other Study ID Numbers: 029-2019

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