Transcranial MRgFUS for Movement Disorders

Not currently 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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new treatment called ExAblate Transcranial MRgFUS, a non-invasive procedure using focused ultrasound, to assist people with movement disorders unresponsive to standard treatments. The goal is to determine if this method can create a small lesion in the brain to reduce symptoms like tremors, spasms, or tics. The trial seeks participants with persistent movement problems despite previous treatments. Those who have tried medications but still struggle with these symptoms may find this trial suitable. As an unphased trial, it offers a unique opportunity to explore innovative treatment options for 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 prior data suggests that the ExAblate Transcranial MRgFUS is safe for treating movement disorders?

Research has shown that ExAblate Transcranial MRgFUS, a type of MRI-guided focused ultrasound, safely treats movement disorders like essential tremor and Parkinson's tremor. This technology targets and treats specific brain areas without surgery by precisely focusing ultrasound energy, reducing risks.

Some patients have experienced mild side effects, such as headaches or temporary numbness, but these effects usually resolve quickly. The treatment has been well-tolerated, with many patients experiencing significant symptom improvement. While researchers continue to study the ExAblate system for safety and effectiveness, its use in treating other conditions suggests it is likely safe. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Transcranial MR-guided Focused Ultrasound (MRgFUS) for movement disorders because it offers a non-invasive alternative to traditional surgical treatments like deep brain stimulation. Unlike standard options that require incisions and implanted devices, MRgFUS uses precise ultrasound waves to target and treat affected brain areas without the need for open surgery. This method reduces recovery time and potential complications, making it a promising option for patients looking for less invasive solutions. Additionally, the real-time MRI guidance allows for precise targeting, which could lead to improved outcomes and fewer side effects.

What evidence suggests that ExAblate Transcranial MRgFUS is effective for movement disorders?

Research has shown that ExAblate Transcranial MRgFUS, a treatment using focused ultrasound with MRI guidance, effectively addresses movement disorders. This treatment targets and heats specific brain areas to ease symptoms. Studies have found success in treating conditions like essential tremor and Parkinson's tremor by creating precise changes in the brain. Patients in these studies reported significant symptom improvements after treatment. This method offers promise for those who haven't found relief with other therapies. Participants in this trial will receive the Transcranial ExAblate System as the experimental treatment. ^{1 2 3 4 6}

Who Is on the Research Team?

Andres Lozano, MD

Principal Investigator

Sunnybrook Health Sciences Centre

Are You a Good Fit for This Trial?

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

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

You have a movement disorder that has not improved with treatment, as confirmed by a movement disorder specialist.

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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

Published Research Related to This Trial

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]

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]

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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/ct2/show/NCT02252380?term=NCT02252380&rank=1

NCT02252380 | ExAblate Transcranial MRgFUS for the ... The purpose of this study is to evaluate the safety and initial effectiveness of MRI-guided focused ultrasound thermal ablation of a designated area in the ...

2. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf15/P150038S006B.pdf

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) The treatment effect using Exablate Neuro Type 1.0 and Type 1.1 is achieved by accurately guiding the focus of the ultrasound energy to the target region. The ...

3. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4687492/

Transcranial MR-Guided Focused Ultrasound - PubMed Central Transcranial MRgFUS has been successfully used for the treatment of movement disorders, including essential tremor(8) and Parkinson tremor(9), as well as for ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT01304758

ExAblate Transcranial MR Guided Focused Ultrasound in ... The purpose of this study is to evaluate the safety and initial effectiveness of MRI-guided focused ultrasound thermal ablation of a designated ...

5. clinicaltrials.stanford.edu clinicaltrials.stanford.edu/trials/e/NCT02037217.html

ExAblate Transcranial MR Guided Focused Ultrasound in the ... A feasibility Study to Evaluate Safety and Initial Effectiveness of ExAblate Transcranial MRI-guided focused ultrasound (MRgFUS) treatment of ...

6. cms.gov cms.gov/medicare-coverage-database/view/lcd.aspx?LCDId=37729

Magnetic-Resonance-Guided Focused Ultrasound Surgery ... The authors conclude that “MRgFUS is a promising therapy with the potential to replace DBS for patients who cannot tolerate DBS, the standard surgical treatment ...