Investigating LFP Correlates of TUS in Patients With Movement Disorders (TUS-LFP)

October 6, 2023 updated by: University Health Network, Toronto

Investigating Local Field Potential Correlates of Transcranial Ultrasound Stimulation in Patients With Movement Disorders

Transcranial Ultrasound Stimulation (TUS) is an emerging non-invasive brain stimulation(NIBS) technique that can be used on both superficial and deep brain targets with a high spatial resolution as small as a few cubic millimeters. Neural correlates of TUS have yet been elucidated. To date, no intracranial recordings (i.e., local field potential [LFP]) have been captured during or after TUS in patients with movement disorders. In this study, we are aiming to profile basal ganglia LFP activity during and after TUS by using a DBS system that is capable of recording LFP. This can shed light on mechanisms of TUS, as well as allow identification of a neurophysiological biomarker that can be used to tune the TUS sonication parameters for future clinical trials.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

Experiment 1: Subjects will be randomly assigned to either the sham or active stimulation group during the first study visit. In the second study visit, there will be a crossover between the groups, with all subjects undergoing one sham and one active stimulation visit before the study is completed. During the active stimulation visit, a theta burst protocol (Isppa: 30 W/cm2, burst length: 20 ms, period: 200 ms, frequency 500 kHz) will be used to sonicate the bilateral primary motor cortices (M1) or globus pallidus interna (GPi) for 2 minutes. The sham group involves sonications performed with the power set to 0 watts over bilateral M1s/GPis. In both groups, the subjects will be masked using white noise transmitted through earbuds. The targets will be identified anatomically using structural MRIs and a neuronavigation system.

The Percept PC DBS system will be used to record local field potentials (LFPs) from the subthalamic nucleus (STN) or globus pallidus internus (GPI) at various time points: before (baseline) and during the sonications, as well as at 10-, 30-, and 45-minute intervals after the sonications. These recordings will be obtained while the subjects engage in a finger tapping task monitored by an accelerometer, as well as during resting periods. The power of LFPs across different frequencies will be compared and correlated with the velocity observed during the finger tapping task.

Following the completion of sham and active stimulation visits, the subjects will have the opportunity to participate in an optional control group visit, which entails sonication of the occipital cortex utilizing the theta burst protocol.

Experiment 2: TUS will be utilized to target the area directly over the DBS lead, while concurrently recording LFPs to identify any stimulation artifact indicative of target area-sonication engagement.

Study Type

Interventional

Enrollment (Estimated)

25

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 Contact

Study Contact Backup

Study Locations

  • Canada
    • Ontario
      • Toronto, Ontario, Canada, M5T 2S8
        • Recruiting
        • Toronto Western Hospital
        • Contact:

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 = M1/GPi Stimulation parameters = Theta burst protocol and 30 Watts
Device: TUS Active
Bilateral M1s/GPis will be sonicated using NeuroFUS device for two minutes per hemisphere with theta burst protocol and 30 W/cm2 Isppa
Sham Comparator: Sham Low Intensity Transcranial Focused Ultrasound
NeuroFUS device stimulation with 4 channel transducer Stimulation target = M1/GPi Stimulation parameters = Theta burst protocol and 0 Watts
Device: TUS Sham
Bilateral M1s/GPis will be sonicated using NeuroFUS device for two minutes per hemisphere with theta burst protocol and 0 W/cm2 Isppa

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
LFP power (Experiment 1)
Time Frame: 5 minutes long recordings during both study visits at 1) Baseline (20-30 minutes before sonication), 2) during sonication, 3) 10 minutes after sonication, 4) 30 minutes after sonication, and 5) 45 minutes after sonication
The change of power of LFPs across different frequencies
5 minutes long recordings during both study visits at 1) Baseline (20-30 minutes before sonication), 2) during sonication, 3) 10 minutes after sonication, 4) 30 minutes after sonication, and 5) 45 minutes after sonication
Stimulation artifact (Experiment 2)
Time Frame: Online during sonications
Presence of a stimulation artifact during LFP recordings
Online during sonications

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
UPDRS (Experiment 1)
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 120 and 130 minutes after the study visit initiation).
Change of UPDRS score
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 120 and 130 minutes after the study visit initiation).
Finger tapping task (Experiment 1)
Time Frame: LFPs during finger tapping will be recorded at each visit for half minute at 1) Baseline (20-30 minutes before sonication), 2) 10 minutes after sonication, 3) 30 minutes after sonication, and 4) 45 minutes after sonication
Correlation of LFP power change with the velocity change during finger tapping task as recorded by an accelerometer
LFPs during finger tapping will be recorded at each visit for half minute at 1) Baseline (20-30 minutes before sonication), 2) 10 minutes after sonication, 3) 30 minutes after sonication, and 4) 45 minutes after sonication
Adverse effect profile (Experiment 1 and 2)
Time Frame: From the initiation of the study up to 1 day after its completion.
Presence of adverse effects as reported subjectively by the patient
From the initiation of the study up to 1 day after its completion.

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)

May 18, 2023

Primary Completion (Estimated)

June 1, 2024

Study Completion (Estimated)

June 1, 2024

Study Registration Dates

First Submitted

June 7, 2023

First Submitted That Met QC Criteria

July 25, 2023

First Posted (Actual)

July 28, 2023

Study Record Updates

Last Update Posted (Estimated)

October 10, 2023

Last Update Submitted That Met QC Criteria

October 6, 2023

Last Verified

July 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 20-5740#2

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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