Transcranial MRgFUS for Movement Disorders

Recruiting at 1 trial location

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: InSightec

Must not be taking: Anti-arrhythmics

Disqualifiers: Unstable cardiac, Severe hypertension, Coagulopathy, Neurodegenerative diseases, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 1

Duration: 1 day

10 Participants Needed

Trial Summary

What is the purpose of this trial?

The proposed study is to evaluate the effectiveness of ExAblate Transcranial MRgFUS as a tool for creating a unilateral lesion in the Vim thalamus or the globus pallidus (GPi) in patients with treatment-refractory symptoms of movement disorders.

Do I need to stop my current medications for the trial?

You will need to keep your medication doses stable for 30 days before joining the study and throughout the trial.

What data supports the effectiveness of the treatment ExAblate Transcranial MRgFUS for movement disorders?

Research shows that MRgFUS, including the ExAblate system, is effective in treating essential tremor and tremor-predominant Parkinson's disease by precisely targeting and treating specific areas in the brain without surgery. This treatment has been shown to reduce tremors and improve patient outcomes. ^{1 2 3 4 5}

Is Transcranial MRgFUS generally safe for humans?

Transcranial MRgFUS has been used safely in humans for conditions like Parkinson's disease and essential tremor. Most reported side effects are mild and temporary, but more research is needed to fully understand its long-term safety. ^{1 6 7 8 9}

How is the ExAblate Transcranial MRgFUS treatment different from other treatments for movement disorders?

ExAblate Transcranial MRgFUS is unique because it uses focused ultrasound waves guided by MRI to target and treat specific brain areas without any incisions, offering a non-invasive alternative to traditional surgical methods for movement disorders like essential tremor and Parkinson's disease. ^{1 2 4 10 11}

Research Team

Andres Lozano, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Eligibility Criteria

This trial is for adults aged 18-85 with treatment-resistant movement disorders like Tardive Dyskinesia, Dystonia, and various forms of Tremor. Participants must have stable medication doses for 30 days prior and be able to communicate during treatment. Exclusions include a history of brain hemorrhage or seizures, bleeding risks, brain tumors, infections, HIV positivity, recent participation in other trials, inability to lie still supine for long periods or give consent.

Inclusion Criteria

People who are between 18 and 85 years old, including both men and women.

Subjects who are able and willing to give consent and able to attend all study visits

Stable doses of all medications for 30 days prior to study entry and for the duration of the study

Exclusion Criteria

You have a history of bleeding inside the brain.

You have had a seizure in the past year.

You have a low platelet count or a bleeding disorder that could cause problems during or after surgery.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo MRI-guided focused ultrasound thermal ablation to create a unilateral lesion in the Vim thalamus or globus pallidus

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment, with follow-up evaluations up to 12 months

12 months

Treatment Details

Interventions

• ExAblate Transcranial MRgFUS

Trial Overview The study tests the effectiveness of the ExAblate Transcranial MRgFUS system in creating lesions within specific brain regions (Vim thalamus or globus pallidus) to alleviate symptoms in patients whose movement disorders haven't improved with standard treatments.

Participant Groups

Group I: Transcranial ExAblate System Experimental Treatment 1 Intervention

Transcranial ExAblate System (MRgFUS)

Who Is Running the Clinical Trial?

InSightec

Lead Sponsor

Trials

92

Recruited

3,800+

Dr. Maurice R. Ferré

InSightec

Chief Executive Officer

MD

Dr. Arjun Desai

InSightec

Chief Medical Officer

MD

Findings from Research

In a study of 31 patients with Essential Tremor treated with MRgFUS, tremor severity significantly decreased, with an average improvement of 45.5% in the Clinical Rating Scale for Tremor and 62.6% in Hand Tremor Scores after treatment.

The effectiveness of MRgFUS was positively linked to the extent of ablation in the posterior dentatorubrothalamic tract, suggesting that targeting this area may enhance treatment outcomes, while older age was associated with less improvement.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Tremor suppression following treatment with MRgFUS: skull density ratio consistency and degree of posterior dentatorubrothalamic tract lesioning predicts long-term clinical outcomes in essential tremor. Kyle, K., Maller, J., Barnett, Y., et al.[2023]

In a study of 29 patients who underwent MRgFUS thalamotomy for tremor-predominant Parkinson's Disease, 96% experienced immediate tremor improvement, and 63% maintained this improvement at a median follow-up of 16 months, indicating the efficacy of this incisionless treatment.

Patient satisfaction was high, with 69% reporting improved quality of life, although 38% experienced mild long-term side effects, particularly related to speech when additional targeting of certain brain areas was performed, which did not enhance tremor control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes After Focused Ultrasound Thalamotomy for Tremor-Predominant Parkinson's Disease. Maragkos, GA., Kosyakovsky, J., Zhao, P., et al.[2023]

The ExAblate Neuro 4000 system uses Magnetic Resonance guided Focused UltraSound (MRgFUS) to precisely target and thermally ablate specific brain tissues, showing promise particularly in treating conditions like Essential Tremor.

Current clinical applications demonstrate that MRgFUS is both safe and effective, but ongoing advancements in technology are needed to enhance its efficacy and expand its use for various neurological diseases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Device profile of exAblate Neuro 4000, the leading system for brain magnetic resonance guided focused ultrasound technology: an overview of its safety and efficacy in the treatment of medically refractory essential tremor. Jameel, A., Bain, P., Nandi, D., et al.[2021]

In a study involving four male patients with essential tremor, bilateral MR-guided focused ultrasound (MRgFUS) treatment resulted in a significant reduction of tremor symptoms, with a decrease in severity of 57.5-69.7% after six months.

No complications were observed in any of the patients, suggesting that simultaneous bilateral thalamotomy using MRgFUS is a safe and effective treatment option for essential tremor.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Experience of staged and simultaneous bilateral thalamotomy using MR-guided focused ultrasound in the treatment of essential tremor]. Nabiullina, DI., Galimova, RM., Illarioshkin, SN., et al.[2023]

The ExAblate device, approved for treating movement disorders like tremor-dominant Parkinson's disease, shows minimal cognitive decline in patients post-treatment, particularly in areas like verbal fluency and inhibition.

Current research on the neurocognitive effects of MRgFUS in Parkinson's disease is limited, with only two studies using comprehensive evaluations, highlighting the need for more rigorous assessments to understand cognitive risks associated with this treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound for Parkinson's disease since ExAblate, 2016-2019: a systematic review. Lennon, JC., Hassan, I.[2022]

In a study of 48 patients with medically refractory tremor-dominant Parkinson's disease, MRgFUS thalamotomy provided significant and sustained tremor control over a follow-up period of up to 3 years.

The procedure was associated with mild side effects, such as gait imbalance and sensory deficits, which were mostly manageable and persisted in some cases, indicating a favorable safety profile.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Focused Ultrasound Thalamotomy for Tremor in Parkinson's Disease: Outcomes in a Large, Prospective Cohort. Chua, MMJ., Blitz, SE., Ng, PR., et al.[2023]

In a study of 180 treatments using incisionless magnetic resonance-guided focused ultrasound (MRgFUS) for chronic therapy-resistant conditions like Parkinson's disease and essential tremor, the procedure demonstrated high targeting accuracy with a mean 3D accuracy of 0.73 mm and a low side-effect profile, with only 14 documented side effects (7.8% of treatments).

The procedure resulted in slight cognitive improvements measured by the Montreal Cognitive Assessment (MoCA) at 2 days and 1 year post-treatment, indicating potential benefits for cognitive function without significant adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and accuracy of incisionless transcranial MR-guided focused ultrasound functional neurosurgery: single-center experience with 253 targets in 180 treatments. Gallay, MN., Moser, D., Jeanmonod, D.[2023]

Magnetic resonance imaging-guided focused ultrasound (MRgFUS) shows potential as a treatment for medication-resistant Parkinson's disease, with 10 out of 11 studies reporting a decline in motor symptoms as measured by UPDRS-III scores, and four studies indicating significant improvements in quality of life.

Most adverse events related to MRgFUS were mild and temporary, suggesting that the treatment is generally safe; however, the overall evidence is limited, highlighting the need for more rigorous studies with larger participant groups and longer follow-up periods.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Safety and efficacy of magnetic resonance imaging-guided focused ultrasound neurosurgery for Parkinson's disease: a systematic review. Xu, Y., He, Q., Wang, M., et al.[2021]

This case study describes the first instance of a functional tremor developing in a 71-year-old man after a successful MR-guided focused ultrasound thalamotomy (MRgFUS) for essential tremor, highlighting a potential complication of this treatment.

Electrophysiological studies confirmed the presence of both essential tremor and a functional tremor, emphasizing the importance of recognizing such complications to prevent unnecessary additional treatments.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Functional tremor developing after successful MRI-guided focused ultrasound thalamotomy for essential tremor. Alshimemeri, S., Vargas-Méndez, D., Chen, R., et al.[2022]

References

1. Switzerland pubmed.ncbi.nlm.nih.gov

Tremor suppression following treatment with MRgFUS: skull density ratio consistency and degree of posterior dentatorubrothalamic tract lesioning predicts long-term clinical outcomes in essential tremor. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

Patient-Reported Outcomes After Focused Ultrasound Thalamotomy for Tremor-Predominant Parkinson's Disease. [2023]

3. England pubmed.ncbi.nlm.nih.gov

Device profile of exAblate Neuro 4000, the leading system for brain magnetic resonance guided focused ultrasound technology: an overview of its safety and efficacy in the treatment of medically refractory essential tremor. [2021]

4. England pubmed.ncbi.nlm.nih.gov

Cognitive outcomes after focused ultrasound thalamotomy for tremor: Results from the COGNIFUS (COGNitive in Focused UltraSound) study. [2023]

5. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Experience of staged and simultaneous bilateral thalamotomy using MR-guided focused ultrasound in the treatment of essential tremor]. [2023]

6. Italy pubmed.ncbi.nlm.nih.gov

Magnetic resonance-guided focused ultrasound for Parkinson's disease since ExAblate, 2016-2019: a systematic review. [2022]

7. United States pubmed.ncbi.nlm.nih.gov

Focused Ultrasound Thalamotomy for Tremor in Parkinson's Disease: Outcomes in a Large, Prospective Cohort. [2023]

8. United States pubmed.ncbi.nlm.nih.gov

Safety and accuracy of incisionless transcranial MR-guided focused ultrasound functional neurosurgery: single-center experience with 253 targets in 180 treatments. [2023]

9. Germany pubmed.ncbi.nlm.nih.gov

Safety and efficacy of magnetic resonance imaging-guided focused ultrasound neurosurgery for Parkinson's disease: a systematic review. [2021]

10. Germany pubmed.ncbi.nlm.nih.gov

Four-tract probabilistic tractography technique for target selection in essential tremor treatment with magnetic resonance-guided focused ultrasound. [2023]

11. England pubmed.ncbi.nlm.nih.gov

Functional tremor developing after successful MRI-guided focused ultrasound thalamotomy for essential tremor. [2022]