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

NCT06232629 | Active Not Recruiting

• 1 other identifier: 20-5740#4
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

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.

Conditions

Parkinson Disease; Dystonia

Keywords

Transcranial Ultrasound Stimulation; Local Field Potential; Globus Pallidus

Outcome Measures

Primary Outcomes (2)

• Any treatment-related adverse events and side effects of TUS applications

  Adverse effects or side effects, as reported by the neurologist participating throughout the study, will be documented. The neurologist will conduct comprehensive neurological assessments, including cranial nerve evaluations, strength tests, sensory and memory examinations, as well as assessments of coordination and reflexes.

  Two assessments will be conducted during each study visit: one at baseline (within the first minute of the study) and the other upon completion of the study visit (between 150 and 180 minutes after the study visit initiation).

• Modulations in the amplitude of the LFP power spectrum

  The power modulations will be measured across different frequencies (theta, alpha, beta) and at different time points (before, during, and after TUS application at each visit).

  4-minute long recordings at 1) Baseline (10 minutes before TUS), 2) during TUS (lasting either 120 seconds or 40 seconds, depending on the protocol), 3) 10 minutes after TUS, 4) 30 minutes after TUS, and 5) 45 minutes after TUS

Secondary Outcomes (1)

• Modulations of the aperiodic activities derived from the LFPs

  4-minute long recordings at 1) Baseline (10 minutes before TUS), 2) during TUS (lasting either 120 seconds or 40 seconds, depending on the protocol), 3) 10 minutes after TUS, 4) 30 minutes after TUS, and 5) 45 minutes after TUS

Study Arms (2)

Active Low-Intensity Transcranial Focused Ultrasound

ACTIVE COMPARATOR

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

Device: TUS Active

Sham Low-Intensity Transcranial Focused Ultrasound

SHAM COMPARATOR

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)

Device: TUS Sham

Interventions

TUS Active 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

Active Low-Intensity Transcranial Focused Ultrasound

TUS Sham 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

Sham Low-Intensity Transcranial Focused Ultrasound

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Adult patients with movement disorders (diagnosed by a movement disorder specialist)
• Implantation of a Percept PC DBS system at least one month before the sonications
• Stable dopaminergic medication dose for a minimum of 4 weeks

You may not qualify if:

• Concomitant neurological conditions (stroke, seizure, dementia, major depression / psychiatric disorders, active drug abuse/addiction and major neuromuscular/musculoskeletal diseases)
• Declined cognitive scores (MoCA score \< 22)
• Implants (cardiac pacemaker, implantable cardioverter-defibrillator, intracranial devices other than DBS system such as shunts and MR- unsafe devices)
• History of intracranial lesioning procedures
• Major systemic illness, infection or pregnancy

Sponsors & Collaborators

• University Health Network, Toronto: lead

Study Sites (1)

Toronto Western Hospital

Toronto, Ontario, M5T 2S8, Canada

Location

MeSH Terms

Conditions

Parkinson Disease; Dystonia

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases; Dyskinesias; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Robert Chen, MBBS

  University Health Network, Toronto

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Masking Details: The subject will be blind to stimulation conditions (sham/active TUS). The assessor will be blind to the stimulation condition (sham/active TUS) while analyzing LFPs.
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Senior Scientist

Study Record Dates

• First Submitted: December 26, 2023
• First Posted: January 31, 2024
• Study Start: August 1, 2023
• Primary Completion: December 31, 2025
• Study Completion (Estimated): December 31, 2026
• Last Updated: September 15, 2025

Record last verified: 2025-09

Data Sharing

• IPD Sharing: Will not share

Locations

CA (1)