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

Primary Purpose

Multiple Sclerosis

Status
Unknown status
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
Focused Ultrasound (MRgFUS) for the Management of Tremor in Patients With Multiple Sclerosis
Sponsored by
Sunnybrook Health Sciences Centre
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional device feasibility trial for Multiple Sclerosis focused on measuring Tremor, Multiple Sclerosis, MR-guided Focused Ultrasound

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

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

Sites / Locations

  • Sunnybrook Health Sciences CentreRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Patients with Multiple Sclerosis and Tremor

Arm Description

Participants will undergo MRgFUS thermal ablation of the ventral intermedius (Vim) thalamus contralateral to the most affected side of the body.

Outcomes

Primary Outcome Measures

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

Secondary Outcome Measures

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.
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.
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.
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.
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.
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.
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.
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

Full Information

First Posted
January 31, 2020
Last Updated
February 19, 2020
Sponsor
Sunnybrook Health Sciences Centre
Collaborators
Multiple Sclerosis Society of Canada
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1. Study Identification

Unique Protocol Identification Number
NCT04279912
Brief Title
MR-Guided Focused Ultrasound (MRgFUS) for the Management of Tremor in Patients With Multiple Sclerosis
Acronym
MSFUS001
Official Title
A Feasibility and Safety Clinical Trial of the Magnetic Resonance Guided Focused Ultrasound (MRgFUS) for the Management of Tremor in Patients With Multiple Sclerosis
Study Type
Interventional

2. Study Status

Record Verification Date
February 2020
Overall Recruitment Status
Unknown status
Study Start Date
January 16, 2020 (Actual)
Primary Completion Date
March 2021 (Anticipated)
Study Completion Date
July 2021 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Sunnybrook Health Sciences Centre
Collaborators
Multiple Sclerosis Society of Canada

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
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).

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Multiple Sclerosis
Keywords
Tremor, Multiple Sclerosis, MR-guided Focused Ultrasound

7. Study Design

Primary Purpose
Device Feasibility
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Model Description
Single-centre, prospective, single-arm, open-label pilot trial assessing the feasibility and safety of MRgFUS thalamotomy for refractory hand tremor in up to 6 patients with multiple sclerosis
Masking
None (Open Label)
Allocation
N/A
Enrollment
6 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Patients with Multiple Sclerosis and Tremor
Arm Type
Experimental
Arm Description
Participants will undergo MRgFUS thermal ablation of the ventral intermedius (Vim) thalamus contralateral to the most affected side of the body.
Intervention Type
Device
Intervention Name(s)
Focused Ultrasound (MRgFUS) for the Management of Tremor in Patients With Multiple Sclerosis
Intervention Description
The intervention is MRIgFUS thermal ablation of the ventral intermedius (Vim) thalamus contralateral to the most affected side of the body.
Primary Outcome Measure Information:
Title
Composite safety outcome of MRgFUS thalamotomy
Description
Composite outcome of detectable Vim lesion on MRI scan; AND lack of new-onset or worsening of contralateral upper limb sensory loss or weakness
Time Frame
90 days
Secondary Outcome Measure Information:
Title
Incidence and severity of adverse events related to MRgFUS thalamotomy
Description
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.
Time Frame
1, 7, 30, 90 and 120 days
Title
Incidence and severity of adverse events related to MS disease relapse or progression
Description
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.
Time Frame
30 and 90 days
Title
Changes from baseline in the EDSS (Expanded Disability Status Scale) scores
Description
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.
Time Frame
30 and 90 days
Title
Changes from baseline in the SARA (Scale for Assessment and Rating of Ataxia) scores
Description
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.
Time Frame
30 and 90 days
Title
Changes from baseline in the speech intelligibility (percentage of intelligible words recorded during standardized passage reading)
Description
Changes from baseline in intelligibility percentage at 30 and 90 days. Score: 0 to 100% with higher scores meaning better outcome.
Time Frame
30 and 90 days
Title
Changes from baseline in QUEST (Quality of Life in Essential Tremor Questionnaire) scores
Description
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.
Time Frame
30 and 90 days
Title
Change from baseline in the CRST (Clinical Rating Scale for Tremors)
Description
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.
Time Frame
30 and 90 days
Title
Composite safety outcome of MRgFUS thalamotomy
Description
Composite outcome of detectable Vim lesion on MRI scan; AND lack of new-onset or worsening of contralateral upper limb sensory loss or weakness
Time Frame
30 days

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Nadia Scantlebury, PhD
Phone
416-480-6100
Ext
4390
Email
nadia.scantlebury@sunnybrook.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Nir Lipsman, MD, PhD
Organizational Affiliation
Sunnybrook Health Sciences Centre
Official's Role
Principal Investigator
First Name & Middle Initial & Last Name & Degree
Agessandro Abrahao, MD, MSc
Organizational Affiliation
Sunnybrook Health Sciences Centre
Official's Role
Principal Investigator
Facility Information:
Facility Name
Sunnybrook Health Sciences Centre
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M4N 3M5
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Nadia Scatlebury, PhD
Phone
+1 416-480-6100
Ext
4390
Email
nadia.scantlebury@sunnybrook.ca

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

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

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