Essential TremorNCT04720469
A Second Magnetic Resonance Guided Focused Ultrasound Thalamotomy for Essential Tremor
A study testing MRgFUS thalamotomy in people with Essential Tremor, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
Trial summary
This study will be a single-centre, prospective, single-arm, open-label, 12-week pilot trial assessing the safety and preliminary efficacy of a second MR-guided focused ultrasound (MRgFUS) thalamotomy on the naïve brain hemisphere after 48 weeks or more of the first MRgFUS thalamotomy in patients with… Read more about this study
- Who is it for?
- Ages 22 years and older
- Conditions the study is for
- Essential Tremor
- What is being tested?
- MRgFUS thalamotomy
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 11 participants
- Where
- 1 siteCanada
- Study dates
- 5 Oct 2020to 18 Mar 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 22 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Individuals aged 22 years or older;
- Subjects who are able and willing to give consent and able to attend all study visits and MRgFUS procedure, understanding the associated risks, benefits, and alternative treatments;
- Diagnosis of ET as confirmed from clinical history and examination by a neurologist or neurosurgeon and unilateral MRgFUS thalamotomy at least 48 weeks prior;
- On a stable dose of medication for tremor for at least 4 weeks;
- Medication-refractory criterion: tremor refractory to adequate trials of at least two medications, one of which should be a first line therapy of either propranolol or primidone. An adequate medication trial is defined as a therapeutic dose of each medication or the development of side effects as the medication dose is titrated;
- Moderate-severe tremor severity criteria in the untreated hand: Despite medical treatment, untreated hand score of ≥2 points in the postural or intention component of the item 5 or 6 in the Part A of CRST, AND untreated hand score of ≥2 points in any one of the items 12-15 of the Part B of CRST;
- Disability criterion: ≥2 points in any one of the Part C items 17-23 as measured by the CRST;
- Able to communicate sensations during the MRgFUS treatment and to press the device STOP button.
Who cannot join
- Patients with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc;
- Women who are pregnant;
- Gait subscore ≥2 points in the SARA scale;
- Speech subscore ≥2 points in the SARA scale;
- Patients with advanced kidney disease (with estimated glomerular filtration rate <30 mL/min/1.73m2) or on dialysis;
- Patients with unstable cardiac status or severe hypertension including:
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- Documented myocardial infarction within six months of enrollment
- Unstable angina on medication
- Unstable or worsening congestive heart failure
- Left ventricular ejection fraction below the lower limit of normal
- History of a hemodynamically unstable cardiac arrhythmia
- Cardiac pacemaker
- Severe hypertension (diastolic BP > 100 on medication);
- Patients exhibiting any behaviour(s) or clinical assessment consistent with ethanol or substance abuse;
- Patients with history of abnormal bleeding, hemorrhage, and/or coagulopathy defined as abnormal coagulation profile (platelet < 100,00/μl), PT (>14 sec) or PTT (>36 sec), and INR > 1.3;
- Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage (e.g. Avastin) within one month of focused ultrasound procedure;
- Ischemic or hemorrhagic stroke within 6 months;
- Patients with brain tumors;
- Individuals who are not able or unwilling to tolerate the required prolonged stationary position during treatment (approximately 2-3 hours);
- Patients who are currently participating in another clinical investigation with an active treatment arm;
- Patients who have had deep brain stimulation (DBS) or a prior stereotactic ablation of the basal ganglia with GKRS or radiofrequency;
- Patients who have been administered botulinum toxins into the arm for 5 months prior to baseline.
- Evidence of clinically important movement disorder, such as chorea, dystonia, or parkinsonism. Anyone with the presence of parkinsonian features including bradykinesia, rigidity, or postural instability will be excluded. Subjects who exhibit only mild resting tremor but no other symptoms or signs of Parkinson's disease may be included.
- Symptoms and signs of increased intracranial pressure (e.g. headache, nausea, vomiting, lethargy, and papilledema);
- Untreated, uncontrolled sleep apnea;
- Presence of any other neurodegenerative disease like multisystem atrophy, progressive supranuclear palsy, dementia with Lewy bodies, and Alzheimer's disease;
- Mild cognitive impairment with impairment in the domain of language as determined by screening neuropsychological battery and judged by study neuropsychologist;
- A known diagnosis of dementia of any cause;
- Uncontrolled major psychiatric disorder or suicidal ideation. Patients with psychiatric disorders identified on initial screening can be treated for these conditions before MRgFUS treatment and enrolled if deemed psychiatrically stable for at least three months before study entry. Any presence of psychosis will be excluded;
- Any illness that in the investigator's opinion preclude participation in this study;
- Patients with a history of seizures within the past year.
- Inability to generate a thermal thalamic lesion during the first MRgFUS procedure;
- Poor tolerance to the first MRgFUS procedure;
- Severe adverse event or moderate-severe adverse event related to the MRgFUS procedure or thalamotomy, such as clinically significant and permanent speech, language, sensory, motor or gait dysfunction.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: A Safety Pilot Clinical Trial of a Second Magnetic Resonance Guided Focused Ultrasound (MRgFUS) Thalamotomy for the Management of Medication-refractory Essential Tremor
This study will be a single-centre, prospective, single-arm, open-label, 12-week pilot trial assessing the safety and preliminary efficacy of a second MR-guided focused ultrasound (MRgFUS) thalamotomy on the naïve brain hemisphere after 48 weeks or more of the first MRgFUS thalamotomy in patients with medication-refractory ET.
This study will be conducted at the Focused Ultrasound Centre of Excellence at Sunnybrook Health Sciences Centre/University of Toronto.
Read the detailed description
Patients who are medication-refractory for ET often require a surgical option to relieve symptoms of ET and improve quality of life. To-date, unilateral MRgFUS has been beneficial in providing patients with some of relief from tremor. However, tasks that require two hands remain a challenge for many patients. Historical risks of bilateral treatment have been an impediment to complete tremor relief. The introduction of MRI and current stereotactic methodologies has significantly reduced the probability of non-target tissue injury. In this study, a second MRgFUS thalamotomy will be performed in a cohort of patients who have already successfully undergone unilateral MRgFUS treatment. Tremor severity, speech, balance, gait, and cognition will be assessed during baseline and follow up visits.
- Conditions
- Essential Tremor
- Being tested
- MRgFUS thalamotomy
- Medical subject headings
- Essential Tremor
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
MRgFUS thalamotomyDevice
Also called ExAblate Neuro
Ablation of untreated thalamus using focused ultrasound to abate tremor.
| Study group | Role | What they receive |
|---|---|---|
| Patients with bilateral essential tremor who have undergone one MRgFUS thalamotomy | Experimental | Patients with bilateral essential tremor who have undergone one MRgFUS thalamotomy Receives: Device: MRgFUS thalamotomy |
What is being measured
The primary outcome is the main question the study is designed to answer.
Incidence at week 12 of new onset or significant worsening of: ataxic gait; speech impairment; cognitive impairment; contralateral weakness; patient-reported disabling sensory loss; Severe AEs related to the MRgFUS procedure.
This composite outcome will be measured by the Scale for the Assessment and Rating of Ataxia (SARA) scale, neuropsychology battery, neurological examination and AE reports.
Measured: 12 weeks
Secondary outcomes (2)
Change in the tremor score (Part A and B) from baseline to 12 weeks after MRgFUS thalamotomy, adjusted for baseline scores.
This CRST subscore will be measured on the treated side.
Measured: 12 weeks
Change in QUEST global score and EQ-5D from baseline to 12 weeks after MRgFUS, adjusted for baseline scores.
QUEST (Quality of Life in Essential Tremor) is a disease-specific quality of life scale.
Measured: 12 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2021
- Study start5 Oct 2020
- Primary completion18 Mar 2024
- Study completion18 Mar 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Essential TremorStudies of the same condition, open and under way.
- More trials run by Sunnybrook Health Sciences CentreThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Model description
- Single-arm, pre/post designl study
- Masking
- None (open label)
- Enrolment
- 11 participants (actual)
Sponsor and investigators
- Lead sponsor
- Sunnybrook Health Sciences Centre
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Agessandro Abrahao, MD, MSc, Principal investigator, Sunnybrook Health Sciences Centre
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04720469
- Sponsor's protocol ID
- 3341
- Status last verified
- Mar 2024
- First submitted
- 5 Nov 2020
- Last updated
- 26 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: Individual participant data can be made available by request and approval of the Sunnybrook REB and study PI.
Study at a glance
From the registry record, last updated by the sponsor on 26 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Safety Pilot Clinical Trial of a Second Magnetic Resonance Guided Focused Ultrasound (MRgFUS) Thalamotomy for the Management of Medication-refractory Essential Tremor
- ClinicalTrials.gov ID
- NCT04720469
- Acronym / sponsor ID
- 3341
- Conditions
- Essential Tremor
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 11 participants (actual)
- Lead sponsor
- Sunnybrook Health Sciences CentreUniversity, hospital or other
- Study start
- 5 Oct 2020 (actual)
- Primary completion
- 18 Mar 2024 (actual)
- Study completion
- 18 Mar 2024 (actual)
- First posted
- 22 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This study will be a single-centre, prospective, single-arm, open-label, 12-week pilot trial assessing the safety and preliminary efficacy of a second MR-guided focused ultrasound (MRgFUS) thalamotomy on the naïve brain hemisphere after 48 weeks or more of the first MRgFUS thalamotomy in patients with medication-refractory ET.
This study will be conducted at the Focused Ultrasound Centre of Excellence at Sunnybrook Health Sciences Centre/University of Toronto.
Detailed description
Patients who are medication-refractory for ET often require a surgical option to relieve symptoms of ET and improve quality of life. To-date, unilateral MRgFUS has been beneficial in providing patients with some of relief from tremor. However, tasks that require two hands remain a challenge for many patients. Historical risks of bilateral treatment have been an impediment to complete tremor relief. The introduction of MRI and current stereotactic methodologies has significantly reduced the probability of non-target tissue injury. In this study, a second MRgFUS thalamotomy will be performed in a cohort of patients who have already successfully undergone unilateral MRgFUS treatment. Tremor severity, speech, balance, gait, and cognition will be assessed during baseline and follow up visits.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
- Model description
- Single-arm, pre/post designl study
| Arm | Type | Receives |
|---|---|---|
| Patients with bilateral essential tremor who have undergone one MRgFUS thalamotomy | Experimental | Device: MRgFUS thalamotomyPatients with bilateral essential tremor who have undergone one MRgFUS thalamotomy |
Who may qualify
- Ages
- 22 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (8 listed)
- Individuals aged 22 years or older;
- Subjects who are able and willing to give consent and able to attend all study visits and MRgFUS procedure, understanding the associated risks, benefits, and alternative treatments;
- Diagnosis of ET as confirmed from clinical history and examination by a neurologist or neurosurgeon and unilateral MRgFUS thalamotomy at least 48 weeks prior;
- On a stable dose of medication for tremor for at least 4 weeks;
- Medication-refractory criterion: tremor refractory to adequate trials of at least two medications, one of which should be a first line therapy of either propranolol or primidone. An adequate medication trial is defined as a therapeutic dose of each medication or the development of side effects as the medication dose is titrated;
Key exclusion criteria (34 listed)
- Patients with standard contraindications for MR imaging such as non-MRI compatible implanted metallic devices including cardiac pacemakers, size limitations, etc;
- Women who are pregnant;
- Gait subscore ≥2 points in the SARA scale;
- Speech subscore ≥2 points in the SARA scale;
- Patients with advanced kidney disease (with estimated glomerular filtration rate <30 mL/min/1.73m2) or on dialysis;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| MRgFUS thalamotomyAlso: ExAblate NeuroAblation of untreated thalamus using focused ultrasound to abate tremor. | Device | Patients with bilateral essential tremor who have undergone one MRgFUS thalamotomy |
Primary outcome
Incidence at week 12 of new onset or significant worsening of: ataxic gait; speech impairment; cognitive impairment; contralateral weakness; patient-reported disabling sensory loss; Severe AEs related to the MRgFUS procedure.
Time frame: 12 weeks
This composite outcome will be measured by the Scale for the Assessment and Rating of Ataxia (SARA) scale, neuropsychology battery, neurological examination and AE reports.
2 secondary outcomes
Change in the tremor score (Part A and B) from baseline to 12 weeks after MRgFUS thalamotomy, adjusted for baseline scores.
Time frame: 12 weeks
Change in QUEST global score and EQ-5D from baseline to 12 weeks after MRgFUS, adjusted for baseline scores.
Time frame: 12 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Apr 2024.
- Sunnybrook Focused Ultrasound Centre of ExcellenceLink provided by the sponsor.
- Individual participant dataSharing planned: No. Individual participant data can be made available by request and approval of the Sunnybrook REB and study PI.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Agessandro Abrahao, MD, MSc principal investigator
Sunnybrook Health Sciences Centre
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing MRgFUS thalamotomy in people with Essential Tremor, run by Sunnybrook Health Sciences Centre at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 8 inclusion and 34 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Apr 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Incidence at week 12 of new onset or significant worsening of: ataxic gait; speech impairment; cognitive impairment; contralateral weakness; patient-reported disabling sensory loss; Severe AEs related to the MRgFUS procedure. (time frame: 12 weeks). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Apr 2024.