Transcranial MRgFUS for Parkinson's Disease

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: InSightec

Must be taking: PD medications

Must not be taking: Neuroleptics, Anticoagulants

Disqualifiers: Severe dyskinesia, Cognitive impairment, Unstable psychiatric disease, others

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

Compensation: Varies

Number of Visits: Unknown

Duration: 4 months

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial tests a new procedure called the ExAblate Transcranial System to determine its safety for treating movement issues in people with Parkinson's Disease. The focus is on addressing motor symptoms not well-managed by medication. Participants are divided into two groups: one receives the actual treatment, while the other initially receives a sham (placebo) treatment but may receive the real one later. Individuals with Parkinson's who experience significant movement problems on one side of their body and find their current medications insufficient may be suitable for this trial. As an unphased trial, this study provides an opportunity to explore innovative treatment options for those seeking alternatives to current medications.

Will I have to stop taking my current medications?

The trial requires that you stay on a stable dose of all Parkinson's Disease medications for 30 days before joining. If you are on anticoagulant or antiplatelet therapy, you must stop these at least one week before the procedure.

What prior data suggests that the ExAblate Transcranial System is safe for treating Parkinson's Disease?

Research has shown that the ExAblate Transcranial System, used to treat Parkinson's Disease symptoms, has been studied for safety. Previous studies found it to be relatively safe, especially for patients with tremors unresponsive to medication.

For example, one study found that MRgFUS (a type of focused ultrasound guided by MRI), part of the ExAblate system, was well-tolerated by participants. Most side effects, if they occurred, were mild and temporary. Another study showed that the ExAblate Neuro system, used in similar treatments, is approved for certain Parkinson's treatments, indicating a recognized level of safety.

In summary, while all treatments carry some risks, earlier research shows promising safety results for the ExAblate Transcranial System. Participants in clinical trials should feel reassured by these findings but should always discuss potential risks with their healthcare provider. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Unlike the standard of care for Parkinson's Disease, which typically includes medications like Levodopa and deep brain stimulation surgery, the ExAblate Transcranial System offers a non-invasive approach. This system uses focused ultrasound waves guided by MRI to precisely target and treat areas of the brain associated with motor symptoms. Researchers are excited about this technique because it doesn't require surgery, potentially reducing recovery time and surgical risks, while still providing relief from symptoms. This novel method could offer an alternative for patients who are not ideal candidates for traditional surgical interventions.

What evidence suggests that the ExAblate Transcranial System is effective for Parkinson's Disease?

Research has shown that the ExAblate Transcranial System, which uses focused ultrasound guided by MRI, may help treat movement problems in people with Parkinson's Disease. In this trial, participants will be assigned to either the ExAblate Treated Arm or the ExAblate Sham Treated Arm. Studies have found that the actual ExAblate treatment can help patients with tremors unresponsive to medication perform daily activities better. A review of several small studies found that people who received this treatment had significant improvements in their movement skills. Additionally, researchers consider it relatively safe and an effective option for patients whose symptoms do not respond well to medication. ^{1 2 3 4 6}

Who Is on the Research Team?

Jeff Elias, MD

Principal Investigator

University of Virginia

Are You a Good Fit for This Trial?

This trial is for men and women aged 30 or older with idiopathic Parkinson's Disease, who can communicate during the procedure, have visible subthalamic nucleus on MRI, respond to Levodopa, and have disabling motor features not well-controlled by medication. Excluded are those with advanced disease stages, severe dyskinesia, other neurodegenerative diseases or strokes, cognitive impairment or significant depression, recent participation in another trial, unstable cardiac status or bleeding disorders.

Inclusion Criteria

Subject is able to communicate sensations during the ExAblate Transcranial procedure

People who are 30 years old or older.

You have been diagnosed with Parkinson's disease by a movement disorder neurologist using specific criteria.

Exclusion Criteria

You are at stage 2.5 or higher on the Hoehn and Yahr scale when taking your medication.

You have severe difficulty with movement as determined by specific questions on a medical assessment.

You have signs of other brain diseases, such as multisystem atrophy, progressive supranuclear palsy, corticobasal syndrome, dementia with Lewy bodies, or Alzheimer's disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive either ExAblate Transcranial System subthalamotomy or sham treatment for motor symptoms of Parkinson's Disease

4 months

Multiple visits for treatment and monitoring

Follow-up

Participants are monitored for safety and effectiveness after treatment

12 months

Regular follow-up visits

What Are the Treatments Tested in This Trial?

Interventions

• ExAblate Transcranial System

Trial Overview The safety of using the ExAblate Transcranial System for subthalamotomy in treating Parkinson's Disease motor symptoms is being tested. This non-invasive technique focuses ultrasound waves to target brain areas involved in movement control.

How Is the Trial Designed?

Group I: ExAblate Treated Arm Experimental Treatment 1 Intervention

ExAblate Transcranial System subthalamotomy for motor symptoms of Parkinson's Disease.

Group II: ExAblate Sham Treated Arm Placebo Group 1 Intervention

ExAblate Transcranial System sham subthalamotomy for motor symptoms of Parkinson's Disease. Sham subjects completing the 4 Month visit may be offered the actual ExAblate subthalamotomy.

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 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]

The study presents an optimized strategy for performing pallidothalamic tractotomy (PTT) using MR-guided focused ultrasound (MRgFUS) in patients with chronic therapy-resistant Parkinson's disease, based on detailed histological analysis of 6 human brain hemispheres.

A standardized target coverage for PTT was established, involving 5 to 7 preplanned lesion sub-units, which enhances the precision and effectiveness of the procedure while maintaining thermal dose control.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Anatomical and Technical Reappraisal of the Pallidothalamic Tractotomy With the Incisionless Transcranial MR-Guided Focused Ultrasound. A Technical Note. Gallay, MN., Moser, D., Federau, C., et al.[2020]

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 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 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]

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 involving 10 patients with early-stage tremor-dominant Parkinson's disease who underwent MRgFUS thalamotomy, the procedure was found to effectively reduce tremors without the need to increase dopaminergic medication over 6 months.

In contrast, a control group of 20 patients on standard dopaminergic therapy showed a significant increase in their medication dosage, highlighting the potential of MRgFUS as a beneficial alternative treatment.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Magnetic Resonance-Guided Focused Ultrasound Thalamotomy May Spare Dopaminergic Therapy in Early-Stage Tremor-Dominant Parkinson's Disease: A Pilot Study. Golfrè Andreasi, N., Cilia, R., Romito, LM., et al.[2023]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT02263885

ExAblate Transcranial MRgFUS of the Globus Pallidum for ... The purpose of this study is to evaluate the safety and initial clinical effectiveness of ExAblate Transcranial unilateral thermal ablation of the globus ...

2. clinicaltrials.gov clinicaltrials.gov/study/NCT02003248

NCT02003248 | A Feasibility Study to Evaluate Safety and ... The proposed study is to evaluate the safety and initial effectiveness of the ExAblate Transcranial MRI-guided focused ultrasound (MRgFUS) treatment of ...

3. accessdata.fda.gov accessdata.fda.gov/cdrh_docs/pdf15/P150038S037B.pdf

SUMMARY OF SAFETY AND EFFECTIVENESS DATA (SSED) The Exablate Neuro is indicated for use in the unilateral pallidothalamic tractotomy of advanced idiopathic Parkinson's Disease with medication- ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10749343/

Efficacy and safety of magnetic resonance-guided focused ... MRgFUS offers an effective and relatively safe treatment option for patients with drug-resistant PD-related tremor.

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

Magnetic-Resonance-Guided Focused Ultrasound Surgery ... A meta-analysis of two small RCTs found significant improvement in the ability of patients with Parkinson's disease, who received MRgFUS, to perform daily ...

6. 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 ...