Focused Ultrasound for Tremors in Parkinson's Disease

Overseen By Juana MA Ayala Castaneda, MSc

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of British Columbia

Must not be taking: Duodopa, Deep brain stimulation

Disqualifiers: Atypical Parkinsonism, Dementia, Neurological disease, 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 treatment called Low Intensity Focused Ultrasound, a non-invasive brain stimulation technique, to reduce tremors in people with Parkinson's disease. The researchers aim to determine if targeting the Zona Incerta is more effective than the current target, the ventral intermediate nucleus, for reducing tremors. Participants are divided into two groups, each receiving the ultrasound treatment in a different order. The trial seeks individuals diagnosed with Parkinson's disease who experience resting tremors and are willing to shave a small area above the ear for the procedure. As an unphased trial, this study offers a unique opportunity to contribute to groundbreaking research that could improve treatment options for Parkinson's disease.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you cannot participate if you've changed your Parkinson's medication in the last two weeks or if you are receiving certain treatments like Duodopa or deep brain stimulation.

What prior data suggests that this focused ultrasound technique is safe for treating tremors in Parkinson's disease?

Research has shown that Magnetic Resonance guided Focused Ultrasound (MRgFUS) is generally safe and can help reduce tremors in people with Parkinson's disease and essential tremor. This technique is approved for treating tremor symptoms in Parkinson's disease in the United States and other countries.

Several studies have tested focused ultrasound and found it safe for treating movement disorders like tremors. Side effects have been minimal, indicating that most patients handle the treatment well.

The treatment uses low-intensity focused ultrasound to stimulate the brain without surgery. As a non-invasive method, it avoids the risks of infection or complications associated with surgery.

Overall, this method appears promising for those dealing with tremors, with studies supporting its safety and effectiveness. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Low Intensity Focused Ultrasound (LIFU) for treating tremors in Parkinson's disease because it offers a non-invasive alternative to current treatments like medications and deep brain stimulation. Unlike traditional options, LIFU uses sound waves to target specific brain areas without the need for surgery, potentially reducing risks and recovery time. Additionally, LIFU allows for precise targeting, which may lead to better control of tremors with fewer side effects. This innovative approach could significantly improve the quality of life for individuals with Parkinson's disease.

What evidence suggests that Low Intensity Focused Ultrasound is effective for reducing tremors in Parkinson's disease?

Research has shown that Magnetic Resonance guided Focused Ultrasound (MRgFUS) can help reduce tremors in people with Parkinson's disease (PD). This treatment is already approved for managing tremor symptoms in PD. Initially, patients with essential tremor responded better, but over time, both groups experienced similar improvements. This trial will compare two approaches: one arm will receive Low Intensity Focused Ultrasound (LIFU) stimulation targeting the ventral intermediate nucleus (Vim) of the thalamus first, while the other arm will receive LIFU stimulation targeting the Zona Incerta (ZI) first. Recent studies suggest that targeting the ZI might be more helpful for PD patients. Researchers are also studying how this treatment changes brain activity. ^{1 2 3 6 7}

Who Is on the Research Team?

Hongchae Baek, PhD

Principal Investigator

Food and Drugs Administration

Soojin Lee, PhD

Principal Investigator

University of British Columbia

Martin J. McKeown, MD, FRCPC

Principal Investigator

University of British Columbia

Are You a Good Fit for This Trial?

This trial is for Parkinson's Disease patients who experience tremors. It aims to help those who haven't found relief with standard treatments. Participants should be able to undergo MRI scans and focused ultrasound procedures.

Inclusion Criteria

Resting tremor score (MDS-UPDRS III 3.17 Rest Tremore Amplitude (RUE or LUE)) ≥ 2

I am between 40 and 80 years old.

I have been diagnosed with Parkinson's disease.

Exclusion Criteria

I have a history of essential tremor.

I do not have dementia affecting my ability to understand this consent.

Individuals should also not participate if they have any of the following contraindications for undergoing fMRI scanning: Cardiac pacemaker, wires, or defibrillator; Metal in eye or orbit, including the history of any eye injury involving metal fragments and increased risk due to (history of) working as a metal worker (grinding, machining, or welding); Ferromagnetic aneurysm clip; Possibility of pregnancy; Artificial heart valve; Ear or eye implant, including cochlear implant; Brain aneurysm clip; Implanted drug infusion pump; Electrical stimulator to nerves or bones; Coil, catheter, or filter in any blood vessel; Orthopedic hardware (artificial joint, plate, screw, rod); Other metallic prostheses; Shrapnel, bullets, or other metal fragments; Surgery, piercings or tattoos (including tattooed eyeliner) in the last six weeks; Medication releasing skin patches (i.e. nicotine, birth control, nitroglycerine); History of claustrophobia

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants receive low-intensity focused ultrasound (LIFU) targeting the Zona Incerta (ZI) and ventral intermediate nucleus (Vim) for tremor control

1 day

1 visit (in-person)

Follow-up

Participants are monitored for changes in functional connectivity and tremor reduction using fMRI and finger acceleration measurements

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Low Intensity Focused Ultrasound

Trial Overview The study tests low intensity focused ultrasound on a brain area called the Zona Incerta, comparing it with current methods targeting the thalamus. Researchers will use simulations and MRIs to find optimal settings and assess brain activity changes.

How Is the Trial Designed?

Group I: ZI first Experimental Treatment 1 Intervention

Participants assigned to this arm get LIFU stimulation in the Vim before the ZI.

Group II: Vim first Experimental Treatment 1 Intervention

Participants assigned to this arm get LIFU stimulation in the Vim before the ZI.

Who Is Running the Clinical Trial?

University of British Columbia

Lead Sponsor

Trials

1,506

Recruited

2,528,000+

Focused Ultrasound Foundation

Collaborator

Trials

18

Recruited

460+

Published Research Related to This Trial

In a study of 123 patients undergoing magnetic resonance-guided focused ultrasound for tremor, those with lower skull density ratios were three times more likely to experience moderate or severe headaches, suggesting that tailored analgesic prophylaxis may be beneficial for these patients.

Women were found to have a significantly higher likelihood of experiencing nausea compared to men, with four times the odds, indicating a need for gender-specific considerations in managing side effects during the procedure.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Factors Associated with Headache and Nausea During Magnetic Resonance-Guided Focused Ultrasound for Tremor. Cacho-Asenjo, E., Honorato-Cia, C., Nuñez-Cordoba, JM., et al.[2022]

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]

Transcranial MR-guided focused ultrasound has shown promise as a safe and effective treatment for functional neurological disorders, with clinical trials demonstrating its ability to create thermal lesions.

Preclinical studies suggest that focused ultrasound can also disrupt the blood-brain barrier and provide reversible neuromodulation, indicating potential for broader therapeutic applications.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The emerging role of transcranial magnetic resonance imaging-guided focused ultrasound in functional neurosurgery. Weintraub, D., Elias, WJ.[2022]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10461511/

Low intensity focused ultrasound: a new prospect for the ... Low-intensity focused ultrasound (LIFU), a new method to stimulate the brain and open the blood-brain barrier (BBB), has been widely concerned by PD ...

2. fusfoundation.org fusfoundation.org/diseases-and-conditions/parkinsons-disease/

Parkinson's Disease Focused ultrasound is cleared to treat both the symptoms of tremor-dominant Parkinson's disease and dyskinesia within and outside the US.

3. clinicaltrials.gov clinicaltrials.gov/study/NCT06259708

Using Low Intensity Focused Ultrasound to Modulate Deep ... Researchers have found that a treatment called Magnetic Resonance guided Focused Ultrasound (MRgFUS) can effectively reduce tremors in patients ...

4. sciencedirect.com sciencedirect.com/science/article/abs/pii/S1474442225002108

Focused ultrasound therapy for movement disorders Several randomised controlled trials have shown safety and symptomatic efficacy of focused ultrasound ablation, particularly to treat patients with essential ...

5. tandfonline.com tandfonline.com/doi/abs/10.1080/07853890.2023.2251145

Low intensity focused ultrasound: a new prospect for the ... Results: Current preclinical studies have shown that LIFU could improve PD motor symptoms by regulating microglia activation, increasing neurotrophic factors, ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12063574/

High Intensity Focused Ultrasound – Longitudinal Data on ... High intensity focused ultrasound (HiFU) is a relatively new incisionless intervention used for treatment of essential tremor and Parkinson's disease tremor.

7. thelancet.com thelancet.com/journals/laneur/article/PIIS1474-4422(25)00210-8/abstract

Focused ultrasound therapy for movement disorders Several randomised controlled trials have shown safety and symptomatic efficacy of focused ultrasound ablation, particularly to treat patients with essential ...