Towards Noninvasive DBS of the Basal Ganglia in Parkinson's Disease Using TUS

NCT ID: NCT06232629

Last Updated: 2025-09-15

Basic Information

• Recruitment Status: ACTIVE_NOT_RECRUITING
• Clinical Phase: NA
• Total Enrollment: 10 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-01
• Study Completion Date: 2026-12-31

Brief Summary

Transcranial Ultrasound Stimulation (TUS) is an emerging non-invasive brain stimulation technique capable of targeting both superficial and deep brain areas with high spatial resolution, down to a few cubic millimeters. In this study, the investigators aim to use TUS to non-invasively modulate the globus pallidus internus (GPi) in patients with Parkinson's disease (PD) and dystonia. These patients have previously been implanted with deep brain stimulation (DBS) leads. The investigators plan to simultaneously record local field potentials (LFPs) from the DBS leads using the Percept PC device (Medtronic Inc.) while the DBS is turned off. The study's goal is to investigate the mechanism of action of TUS and its neuromodulatory effects on LFPs recorded from the GPi. This will enable us to compare the effects of TUS with those of DBS.

Detailed Description

Study Participants and Visits: The investigators will recruit 10-15 PD and dystonia patients who have undergone DBS with lead locations at the GPi. These participants will be involved in three study visits.

First Visit - MRI Scanning: During the first visit, participants will undergo a structural MRI scan, including T1 and T2 scans, at the Toronto Western Hospital using a 3.0 T Siemens MR-imager. These scans are crucial for transcranial ultrasound modeling to accurately localize the targets.

Second and Third Visits - Transcranial Ultrasound Stimulation (TUS): For the second and third visits, the investigators will use the Brainsight system and BabelBrain, an open source application, to neuronavigate the TUS transducer (NeuroFUS system). This process involves sonication of the GPi, with individualized modeling and simulations to account for ultrasound losses due to variations in skull density and morphology. The investigators will target the GPi bilaterally (where the DBS electrodes are located) and record local field potentials (LFPs) before, during, and up to one hour post TUS.

TUS Protocols: Patients will undergo two different TUS protocols across the recording visits, assigned in random order and spaced at least one week apart. The protocols include:

A tbTUS protocol (5Hz Pulse Repetition Frequency [PRF]), previously shown to increase motor cortex excitability for about one hour after sonication and a 10Hz protocol, which has been demonstrated to inhibit motor cortical activity for about one hour post sonication.

Additionally, the investigators will administer two sham-TUS protocols at each visit, randomly selected to assess placebo effects and the impact of somatosensory stimulation associated with TUS.

The sham protocols are an active sham-TUS for which the investigators will sonicate the occipital cortex (Isppa: 30 W/cm2) using either 5 or 10 Hz protocols, and a passive sham-TUS for which the GPi will be sonicated with either 5 or 10 Hz protocols but at zero power (Isppa: 0 W/cm2).

Conditions

Parkinson Disease; Dystonia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: BASIC_SCIENCE
• Blinding Strategy: DOUBLE

Study Groups

Active Low-Intensity Transcranial Focused Ultrasound

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

Group Type: ACTIVE_COMPARATOR

TUS Active

Intervention Type: DEVICE

Bilateral GPis will be sonicated using NeuroFUS device for either two minutes (5Hz protocol) or 40 seconds (10 Hz protocol) per hemisphere and with 30 W/cm2 Isppa

Sham Low-Intensity Transcranial Focused Ultrasound

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)

Group Type: SHAM_COMPARATOR

TUS Sham

Intervention Type: DEVICE

Passive sham: Bilateral GPis will be sonicated using NeuroFUS device for two minutes (5Hz protocol) or 40 seconds (10 Hz protocol) per hemisphere and 0 W/cm2 Isppa

Active sham: Bilateral occipital cortices will be sonicated using NeuroFUS device for two minutes (5Hz protocol) or 40 seconds (10 Hz protocol) per hemisphere and 30 W/cm2 Isppa

Interventions

TUS Active

Bilateral GPis will be sonicated using NeuroFUS device for either two minutes (5Hz protocol) or 40 seconds (10 Hz protocol) per hemisphere and with 30 W/cm2 Isppa

Intervention Type: DEVICE

TUS Sham

Passive sham: Bilateral GPis will be sonicated using NeuroFUS device for two minutes (5Hz protocol) or 40 seconds (10 Hz protocol) per hemisphere and 0 W/cm2 Isppa

Active sham: Bilateral occipital cortices will be sonicated using NeuroFUS device for two minutes (5Hz protocol) or 40 seconds (10 Hz protocol) per hemisphere and 30 W/cm2 Isppa

Intervention Type: DEVICE

Eligibility Criteria

Inclusion Criteria

1. Adult patients with movement disorders (diagnosed by a movement disorder specialist)

2. Implantation of a Percept PC DBS system at least one month before the sonications

3. Stable dopaminergic medication dose for a minimum of 4 weeks

Exclusion Criteria

1. Concomitant neurological conditions (stroke, seizure, dementia, major depression / psychiatric disorders, active drug abuse/addiction and major neuromuscular/musculoskeletal diseases)

2. Declined cognitive scores (MoCA score < 22)

3. Implants (cardiac pacemaker, implantable cardioverter-defibrillator, intracranial devices other than DBS system such as shunts and MR- unsafe devices)

4. History of intracranial lesioning procedures

5. Major systemic illness, infection or pregnancy

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Health Network, Toronto

OTHER

Sponsor Role: lead

Responsible Party

Robert Chen

Senior Scientist

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Robert Chen, MBBS

Role: PRINCIPAL_INVESTIGATOR

University Health Network, Toronto

Locations

Toronto Western Hospital

Toronto, Ontario, Canada

Countries

Canada

Other Identifiers

20-5740#4

Identifier Type: -

Identifier Source: org_study_id