Transcranial MRgFUS for Parkinson's Disease

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: InSightec

Must not be taking: Anti-arrhythmics, Anticoagulants, Antiplatelets, others

Disqualifiers: Cardiac issues, Severe hypertension, others

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

Compensation: Varies

Number of Visits: 4

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 guided by MRI, for people with Parkinson's disease who experience unwanted movements from their medication. The goal is to determine if this treatment is safe and effective in reducing these movements. The trial seeks participants with Parkinson's who have stable medication doses and can communicate during the procedure.

As an unphased trial, this study provides a unique opportunity for patients to contribute to groundbreaking research and potentially benefit from an innovative treatment.

Will I have to stop taking my current medications?

The trial requires that you stay on stable doses of all your current medications for 30 days before joining and throughout the study.

What prior data suggests that the ExAblate Transcranial MRgFUS is safe for treating dyskinesia in Parkinson's disease?

Research shows that Transcranial ExAblate, a treatment using focused ultrasound guided by MRI, is generally safe for people with Parkinson's disease. Studies have found this method effective and relatively safe, especially for those whose tremors don't improve with medication.

The treatment directs ultrasound energy to a specific part of the brain. Tested in people with Parkinson's disease, many reported being able to perform daily activities more easily after the treatment.

While the treatment is considered safe, some people might experience side effects like headaches or dizziness, though serious issues are rare. Prospective trial participants should consult a doctor to understand how this treatment might work for them. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Transcranial ExAblate MRgFUS because it offers a non-invasive approach to treating Parkinson's disease, unlike standard treatments like medications and deep brain stimulation. This treatment uses focused ultrasound waves guided by MRI to precisely target and disrupt brain regions involved in Parkinson's symptoms without the need for incisions. This innovative method could reduce risks associated with surgery and potentially provide faster relief from symptoms.

What evidence suggests that the ExAblate Transcranial MRgFUS is effective for L-dopa induced dyskinesia in Parkinson's disease?

Research has shown that Transcranial ExAblate, the treatment under study in this trial using MRI-guided focused ultrasound, may alleviate Parkinson's disease symptoms, particularly tremors unresponsive to medication. One study found that this treatment reduced tremors in patients who did not respond well to drugs. It directs ultrasound energy to a specific part of the brain, helping to relieve symptoms. Reviews comparing it to other treatments, such as deep brain stimulation, suggest it is relatively safe. Although more information is needed on its effect on movement problems caused by L-dopa, early results appear promising. ^{2 3 5 6 7}

Are You a Good Fit for This Trial?

This trial is for men and women aged 18-80 with Parkinson's Disease who experience L-dopa induced dyskinesia. Participants must have stable medication doses for 30 days prior, be able to give consent, attend all visits, and communicate during treatment. Excluded are those with severe health issues like brain hemorrhage or tumors, unstable heart conditions, bleeding risks, other neurodegenerative diseases or cognitive impairment.

Inclusion Criteria

Patients 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

Inclusion and exclusion criteria have been agreed upon by two members of the medical team

Exclusion Criteria

You have a history of bleeding inside your brain.

You have an infection that is not being treated or controlled.

You have a serious illness that could be life-threatening.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive ExAblate Transcranial MRgFUS treatment for L-dopa induced dyskinesia

1 day

1 visit (in-person)

Follow-up

Participants are monitored for safety and effectiveness after treatment using clinical rating scales at Baseline, 3-Months, and 12-Months post-treatment

12 months

3 visits (in-person)

What Are the Treatments Tested in This Trial?

Interventions

• Transcranial ExAblate

Trial Overview The study tests the safety and effectiveness of ExAblate Transcranial MRgFUS in treating dyskinesia in Parkinson's patients. It involves using focused ultrasound to target brain areas responsible for movement disorders. Effectiveness will be measured by changes in clinical rating scales at baseline, 3 months and 12 months post-treatment.

How Is the Trial Designed?

Group I: Transcranial ExAblate Experimental Treatment 1 Intervention

Transcranial ExAblate 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

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]

Magnetic resonance-guided focused ultrasound (MRgFUS) significantly improved limb tremor and daily activities in Parkinson's disease patients compared to a sham procedure, based on a pooled analysis of 2 studies with treatment durations of up to 4 months.

While MRgFUS was associated with some adverse events, such as dizziness, there were no serious side effects reported, indicating a favorable safety profile for this treatment approach.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Clinical application of magnetic resonance-guided focused ultrasound in Parkinson's disease: a meta-analysis of randomized clinical trials. Ge, Y., Wang, Z., Gu, F., et al.[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 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 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]

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 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]

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. 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.

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1353802023001542

Magnetic Resonance–Guided focused ultrasound surgery ... Review article. Magnetic Resonance–Guided focused ultrasound surgery for Parkinson's disease: A mini-review and comparison between deep brain stimulation.

4. 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 ...

5. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/40179892/

Transcranial magnetic resonance-guided focused ... This paper presents an industry-focused perspective on the current state of MRgFUS, highlighting recent advancements, challenges, and emerging opportunities ...

6. 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 ...

7. 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 ...