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

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

Researchers have found that a treatment called Magnetic Resonance guided Focused Ultrasound (MRgFUS) can effectively reduce tremors in patients with essential tremor (ET) and Parkinson's disease (PD). They noticed that ET patients initially responded better to the treatment than PD patients, but by the end of the treatment, both groups showed similar improvement. The study also suggested that targeting a specific area of the brain called the Zona Incerta (ZI) may be more beneficial for PD patients. Based on these findings, the investigators plan to use low-intensity focused ultrasound to directly modulate the ZI area and investigate the mechanisms of reduced tremors in PD patients. The investigators will also compare the effectiveness of this approach with the current target, the ventral intermediate nucleus (Vim) of the thalamus. The investigators will use a simulation model to determine the best ultrasound parameters for this new approach and will also examine the impact of the treatment on the brain's network activity using functional Magnetic Resonance Imaging. Success of this project may lay the foundation for finding a more effective target for MRgFUS treatment of PD tremor.

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.

Is focused ultrasound safe for treating tremors in humans?

Focused ultrasound for tremors, including those in Parkinson's disease, is generally considered safe, with most side effects like headache and nausea being mild and temporary. ^{1 2 3 4 5}

How is the Low Intensity Focused Ultrasound treatment for Parkinson's tremors different from other treatments?

Low Intensity Focused Ultrasound (LIFU) is unique because it is a non-invasive treatment that uses sound waves to target specific areas of the brain, potentially offering tremor relief without surgery. Unlike traditional treatments that may involve medication or invasive procedures, LIFU can temporarily open the blood-brain barrier to enhance the delivery of therapeutic agents. ^{3 5 6 7 8}

What data supports the effectiveness of the treatment Low Intensity Focused Ultrasound for tremors in Parkinson's Disease?

Research shows that focused ultrasound, a non-invasive treatment, has been effective in reducing tremors in Parkinson's disease and essential tremor, with studies indicating both short-term and long-term benefits. ^{3 4 5 6 9}

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

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]

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 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]

Citations

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

The emerging role of transcranial magnetic resonance imaging-guided focused ultrasound in functional neurosurgery. [2022]

2. Netherlands pubmed.ncbi.nlm.nih.gov

Focused Ultrasound Thalamotomy in Tremor Dominant Parkinson's Disease: Long-Term Results. [2022]

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

Transcranial MRI-guided high-intensity focused ultrasound for treatment of essential tremor: A pilot study on the correlation between lesion size, lesion location, thermal dose, and clinical outcome. [2019]

4. Italy pubmed.ncbi.nlm.nih.gov

Clinical application of magnetic resonance-guided focused ultrasound in Parkinson's disease: a meta-analysis of randomized clinical trials. [2022]

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

Trial of Globus Pallidus Focused Ultrasound Ablation in Parkinson's Disease. [2023]

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

Accumulated thermal dose in MRI-guided focused ultrasound for essential tremor: repeated sonications with low focal temperatures. [2021]

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

Factors Associated with Headache and Nausea During Magnetic Resonance-Guided Focused Ultrasound for Tremor. [2022]

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

Focused ultrasound thalamotomy for tremor treatment impacts the cerebello-thalamo-cortical network. [2023]

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

Focused ultrasound opening of the blood-brain barrier for treatment of Parkinson's disease. [2020]