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

January 30, 2024 updated by: Robert Chen, University Health Network, Toronto

Towards Noninvasive Deep Brain Stimulation of the Basal Ganglia in Parkinson's Disease Using Low-intensity Transcranial Ultrasound Stimulation

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.

Study Overview

Status

Active, not recruiting

Conditions

Intervention / Treatment

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).

Study Type

Interventional

Enrollment (Estimated)

10

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5T 2S8
        • Toronto Western Hospital

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Basic Science
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: 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
Device: 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
Sham Comparator: 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)
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

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Modulations in the amplitude of the LFP power spectrum
Time Frame: 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
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
Any treatment-related adverse events and side effects of TUS applications
Time Frame: 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).
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).

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Modulations of the aperiodic activities derived from the LFPs
Time Frame: 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
The LFPs will be fitted to classical models of synaptic plasticity. The aperiodic activities derived from the LFPs, along with the results from the synaptic plasticity models, will be compared to investigate the potential mechanisms underlying neuroplasticity induced by TUS.
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

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

University Health Network, Toronto

Investigators

  • Principal Investigator: Robert Chen, MBBS, University Health Network, Toronto

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

August 1, 2023

Primary Completion (Estimated)

February 28, 2024

Study Completion (Estimated)

March 30, 2024

Study Registration Dates

First Submitted

December 26, 2023

First Submitted That Met QC Criteria

January 28, 2024

First Posted (Actual)

January 31, 2024

Study Record Updates

Last Update Posted (Estimated)

February 1, 2024

Last Update Submitted That Met QC Criteria

January 30, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20-5740#4

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

NO

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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