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

7 Participants Needed

Trial Summary

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.

Is transcranial MRgFUS safe for humans?

Transcranial MRgFUS (magnetic resonance-guided focused ultrasound) has been used safely in humans for conditions like Parkinson's disease and essential tremor. Most studies report mild and temporary side effects, and it is considered a potential treatment with a good safety profile. However, more research with larger groups and longer follow-up is needed to fully understand its safety. ^{1 2 3 4 5}

How is the ExAblate Transcranial System treatment different from other Parkinson's disease treatments?

The ExAblate Transcranial System uses magnetic resonance-guided focused ultrasound (MRgFUS) to treat Parkinson's disease without making any incisions, offering a non-invasive alternative to traditional surgical methods. This treatment is unique because it precisely targets and destroys specific brain areas responsible for tremors, potentially reducing the need for dopaminergic drugs. ^{2 6 7 8 9}

What is the purpose of this trial?

This is primarily a safety protocol to evaluate the safety of subthalamotomy using Transcranial ExAblate for treatment of Parkinson's Disease (PD) motor features.

Research Team

Jeff Elias, MD

Principal Investigator

University of Virginia

Eligibility Criteria

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

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

Treatment Details

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.

Participant Groups

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

Findings from Research

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]

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 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 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]

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]

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 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]

References

1. Italy pubmed.ncbi.nlm.nih.gov

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

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

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

3. 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]

4. 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]

5. England pubmed.ncbi.nlm.nih.gov

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

6. United States 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. [2023]

7. 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]

8. Switzerland pubmed.ncbi.nlm.nih.gov

Anatomical and Technical Reappraisal of the Pallidothalamic Tractotomy With the Incisionless Transcranial MR-Guided Focused Ultrasound. A Technical Note. [2020]

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

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