Clinical trial NCT04279912: MR-Guided Focused Ultrasound (MRgFUS) for the Management of Tremor in Patients With Multiple Sclerosis
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
Overall status: UNKNOWN
Phase: NA
Conditions: Multiple Sclerosis
Keywords: Tremor
Multiple Sclerosis
MR-guided Focused Ultrasound
Lead sponsor: Sunnybrook Health Sciences Centre
Sponsor class: OTHER
Collaborators: name: Multiple Sclerosis Society of Canada
First posted: 2020-02-21
Enrollment: 6
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention 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
Primary purpose: DEVICE_FEASIBILITY

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).


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

Primary outcomes:
measure: Composite safety outcome of MRgFUS thalamotomy
timeFrame: 90 days
Secondary outcomes:
measure: Incidence and severity of adverse events related to MRgFUS thalamotomy
timeFrame: 1, 7, 30, 90 and 120 days
measure: Incidence and severity of adverse events related to MS disease relapse or progression
timeFrame: 30 and 90 days
measure: Changes from baseline in the EDSS (Expanded Disability Status Scale) scores
timeFrame: 30 and 90 days
measure: Changes from baseline in the SARA (Scale for Assessment and Rating of Ataxia) scores
timeFrame: 30 and 90 days
measure: Changes from baseline in the speech intelligibility (percentage of intelligible words recorded during standardized passage reading)
timeFrame: 30 and 90 days
measure: Changes from baseline in QUEST (Quality of Life in Essential Tremor Questionnaire) scores
timeFrame: 30 and 90 days
measure: Change from baseline in the CRST (Clinical Rating Scale for Tremors)
timeFrame: 30 and 90 days
measure: Composite safety outcome of MRgFUS thalamotomy
timeFrame: 30 days
Other outcomes:
Locations:
city: Toronto
country: Canada
facility: Sunnybrook Health Sciences Centre
state: Ontario
Study officials:
affiliation: Sunnybrook Health Sciences Centre
name: Nir Lipsman, MD, PhD
role: PRINCIPAL_INVESTIGATOR
affiliation: Sunnybrook Health Sciences Centre
name: Agessandro Abrahao, MD, MSc
role: PRINCIPAL_INVESTIGATOR
References: