Transcranial Ultrasound Stimulation for Parkinson's Disease

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University Health Network, Toronto

Must be taking: Dopaminergic medications

Disqualifiers: Stroke, Seizure, Dementia, others

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

Compensation: Varies

Number of Visits: 3

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores a new treatment called Transcranial Ultrasound Stimulation (TUS). TUS uses focused sound waves to target specific brain areas non-invasively, aiming to help people with Parkinson's disease and dystonia. The trial compares TUS effects with those of an existing treatment, deep brain stimulation (DBS). It suits individuals who have had DBS devices implanted and maintained stable medication for at least four weeks. As an unphased trial, this study offers a unique opportunity to contribute to pioneering research in non-invasive treatments for neurological conditions.

Do I have to stop taking my current medications for the trial?

The trial requires that your dopaminergic medication dose has been stable for at least 4 weeks before participating, so you won't need to stop taking it, but you should not change the dose.

What prior data suggests that this technique is safe for patients with Parkinson's disease?

Research has shown that Transcranial Ultrasound Stimulation (TUS) is generally safe and well-tolerated. In past studies, most participants did not experience serious side effects. Minor issues, such as mild headaches or brief dizziness, were uncommon and short-lived. TUS is a non-invasive method, meaning it doesn't require surgery or breaking the skin, which often enhances its safety.

In one study, researchers confirmed the safe use of TUS by monitoring side effects. The results indicated that the treatment was practical with very few problems reported. Another study found that while TUS can reach deep brain areas, its effects on these areas are still under investigation. Overall, the evidence so far suggests that TUS is a promising and safe method for brain stimulation. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about Transcranial Ultrasound Stimulation (TUS) for Parkinson's disease because it offers a non-invasive approach to targeting specific brain areas, potentially reducing symptoms without the need for surgery or medication. Unlike standard treatments like Levodopa or deep brain stimulation, TUS uses focused sound waves to stimulate the globus pallidus internus (GPi), which could improve motor function. This technique also allows for precise control and adjustment of stimulation parameters, potentially leading to personalized treatment plans tailored to individual patients' needs. The promise of fewer side effects and a more targeted intervention is what makes TUS stand out.

What evidence suggests that Transcranial Ultrasound Stimulation is effective for Parkinson's disease?

Research has shown that Transcranial Ultrasound Stimulation (TUS) can affect brain activity and may help treat neurological conditions. Studies have found that low-intensity TUS can ease symptoms in disorders like Parkinson's disease by targeting specific brain areas. In this trial, participants will receive either Active Low-Intensity Transcranial Focused Ultrasound or Sham Low-Intensity Transcranial Focused Ultrasound. One study discovered that TUS can change brain activity similarly to deep brain stimulation (DBS), but without requiring surgery. This treatment uses sound waves directed at the brain to alter brain circuit function, which might help reduce some Parkinson's symptoms. Early results are promising, but more research is needed to fully understand its effectiveness and safety. ^{1 6 7 8 9}

Who Is on the Research Team?

Robert Chen, MBBS

Principal Investigator

University Health Network, Toronto

Are You a Good Fit for This Trial?

This trial is for adults with Parkinson's Disease or dystonia, diagnosed by a specialist. Participants must have had a Percept PC DBS system implanted at least one month prior and been on a stable dose of dopaminergic medication for at least four weeks.

Inclusion Criteria

I have been diagnosed with a movement disorder by a specialist.

I had a Percept PC DBS system implanted at least a month ago.

My Parkinson's medication dose has been the same for at least 4 weeks.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

First Visit - MRI Scanning

Participants undergo a structural MRI scan, including T1 and T2 scans, for transcranial ultrasound modeling

1 day

1 visit (in-person)

Second and Third Visits - Transcranial Ultrasound Stimulation (TUS)

Participants undergo TUS with two different protocols, with LFPs recorded before, during, and after TUS

2 visits, spaced at least one week apart

2 visits (in-person)

Follow-up

Participants are monitored for safety and effectiveness after TUS sessions

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• TUS

Trial Overview The study tests Transcranial Ultrasound Stimulation (TUS) as a non-invasive alternative to Deep Brain Stimulation (DBS). It aims to modulate brain activity in the globus pallidus internus using TUS while recording local field potentials from previously implanted DBS leads.

How Is the Trial Designed?

Group I: Active Low-Intensity Transcranial Focused Ultrasound Active Control 1 Intervention

NeuroFUS device stimulation with 4-channel transducer Stimulation target = GPi Stimulation parameters = 5Hz and 10 Hz protocols at ISPPA=30 W/cm2

Group II: Sham Low-Intensity Transcranial Focused Ultrasound Placebo Group 1 Intervention

NeuroFUS device stimulation with 4-channel transducer Stimulation target = GPi and occipital cortex Stimulation parameters = for the passive sham protocol: GPi target (5Hz and 10 Hz protocols at 0 ISPPA) and for the active sham protocol: occipital target (5Hz and 10 Hz protocol at 30 ISPPA)

Who Is Running the Clinical Trial?

University Health Network, Toronto

Lead Sponsor

Trials

1,555

Recruited

526,000+

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC9139935/

Low-Intensity Transcranial Ultrasound Stimulation Indeed, increasing ultrasound frequency narrows the stimulation focus but results in greater transcranial attenuation and scattering [15].

2. clinicaltrials.gov clinicaltrials.gov/study/NCT07207122

Effects of Transcranial Ultrasound Stimulation (TUS) on ... The purpose of this study is to evaluate the safety and efficacy of transcranial focused ultrasound neuromodulation in improving neural ...

3. sciencedirect.com sciencedirect.com/science/article/abs/pii/S0149763423004700

The effectiveness and safety of low-intensity transcranial ... Low-intensity transcranial ultrasound stimulation shows therapeutic effects in neurological and psychiatric disorders. •. Low-intensity transcranial ...

4. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10030814/

Transcranial low-intensity ultrasound stimulation for treating ... The present review describes the current status of research on low-intensity transcranial ultrasound stimulation (LITUS) in the treatment of neurological ...

5. neurology.org neurology.org/doi/10.1212/WNL.0000000000203886

Neurophysiological and Clinical Effects of Low-intensity ... Abstract. Objective: Evaluate the neurophysiological and clinical effects of transcranial ultrasound stimulation (TUS) of motor cortex (M1) in PD patients.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC12106416/

Transcranial ultrasound stimulation in neuromodulation Transcranial ultrasound stimulation (TUS) is a non-invasive neuromodulation technique with promising clinical potential.

7. nature.com nature.com/articles/s41467-025-57883-7

Individualized non-invasive deep brain stimulation of the ... Transcranial ultrasound stimulation (TUS) offers precise, non-invasive neuromodulation, though its impact on human deep brain structures remains underexplored.

8. movementdisorders.onlinelibrary.wiley.com movementdisorders.onlinelibrary.wiley.com/doi/10.1002/mds.29622

Accelerated Transcranial Ultrasound Neuromodulation in ... The primary outcomes of the study were feasibility and safe delivery of a-tbTUS as assessed by the occurrence of adverse events reported by ...

9. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC10896933/

Novel ultrasound neuromodulation therapy with ... We present a first retrospective analysis of TPS as an add-on therapy for Parkinson's disease (PD), focusing on feasibility, safety, and clinical effects.