search
Back to results

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

Primary Purpose

Parkinson Disease, Essential Tremor, Dystonia

Status
Recruiting
Phase
Not Applicable
Locations
Canada
Study Type
Interventional
Intervention
TUS Active
TUS Sham
Sponsored by
University Health Network, Toronto
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional basic science trial for Parkinson Disease

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria: 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 Exclusion Criteria: 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

Sites / Locations

  • Toronto Western HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Sham Comparator

Arm Label

Active Low Intensity Transcranial Focused Ultrasound

Sham Low Intensity Transcranial Focused Ultrasound

Arm Description

NeuroFUS device stimulation with 4 channel transducer Stimulation target = M1/GPi Stimulation parameters = Theta burst protocol and 30 Watts

NeuroFUS device stimulation with 4 channel transducer Stimulation target = M1/GPi Stimulation parameters = Theta burst protocol and 0 Watts

Outcomes

Primary Outcome Measures

LFP power (Experiment 1)
The change of power of LFPs across different frequencies
Stimulation artifact (Experiment 2)
Presence of a stimulation artifact during LFP recordings

Secondary Outcome Measures

UPDRS (Experiment 1)
Change of UPDRS score
Finger tapping task (Experiment 1)
Correlation of LFP power change with the velocity change during finger tapping task as recorded by an accelerometer
Adverse effect profile (Experiment 1 and 2)
Presence of adverse effects as reported subjectively by the patient

Full Information

First Posted
June 7, 2023
Last Updated
October 6, 2023
Sponsor
University Health Network, Toronto
search

1. Study Identification

Unique Protocol Identification Number
NCT05965960
Brief Title
Investigating LFP Correlates of TUS in Patients With Movement Disorders
Acronym
TUS-LFP
Official Title
Investigating Local Field Potential Correlates of Transcranial Ultrasound Stimulation in Patients With Movement Disorders
Study Type
Interventional

2. Study Status

Record Verification Date
July 2023
Overall Recruitment Status
Recruiting
Study Start Date
May 18, 2023 (Actual)
Primary Completion Date
June 1, 2024 (Anticipated)
Study Completion Date
June 1, 2024 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
University Health Network, Toronto

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
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.
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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Parkinson Disease, Essential Tremor, Dystonia

7. Study Design

Primary Purpose
Basic Science
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantOutcomes Assessor
Masking Description
The subject will be blind to stimulation condition (sham/active TUS). The assessor will be blind to stimulation condition (sham/active TUS) while analyzing LFPs. The UPDRS examination will be video-recorded and blindly assessed by a research team member.
Allocation
Randomized
Enrollment
25 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Active Low Intensity Transcranial Focused Ultrasound
Arm Type
Active Comparator
Arm Description
NeuroFUS device stimulation with 4 channel transducer Stimulation target = M1/GPi Stimulation parameters = Theta burst protocol and 30 Watts
Arm Title
Sham Low Intensity Transcranial Focused Ultrasound
Arm Type
Sham Comparator
Arm Description
NeuroFUS device stimulation with 4 channel transducer Stimulation target = M1/GPi Stimulation parameters = Theta burst protocol and 0 Watts
Intervention Type
Device
Intervention Name(s)
TUS Active
Intervention Description
Bilateral M1s/GPis will be sonicated using NeuroFUS device for two minutes per hemisphere with theta burst protocol and 30 W/cm2 Isppa
Intervention Type
Device
Intervention Name(s)
TUS Sham
Intervention Description
Bilateral M1s/GPis will be sonicated using NeuroFUS device for two minutes per hemisphere with theta burst protocol and 0 W/cm2 Isppa
Primary Outcome Measure Information:
Title
LFP power (Experiment 1)
Description
The change of power of LFPs across different frequencies
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
Title
Stimulation artifact (Experiment 2)
Description
Presence of a stimulation artifact during LFP recordings
Time Frame
Online during sonications
Secondary Outcome Measure Information:
Title
UPDRS (Experiment 1)
Description
Change of UPDRS score
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).
Title
Finger tapping task (Experiment 1)
Description
Correlation of LFP power change with the velocity change during finger tapping task as recorded by an accelerometer
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
Title
Adverse effect profile (Experiment 1 and 2)
Description
Presence of adverse effects as reported subjectively by the patient
Time Frame
From the initiation of the study up to 1 day after its completion.

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: 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 Exclusion Criteria: 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
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Julian Kwok
Phone
1 416 603 5800
Ext
2708
Email
julian.kwok@uhn.ca
First Name & Middle Initial & Last Name or Official Title & Degree
Can Sarica, MD
Phone
1 437 777 2269
Email
can.sarica@mail.utoronto.ca
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Robert Chen, MBBS
Organizational Affiliation
University Health Network, Toronto
Official's Role
Principal Investigator
Facility Information:
Facility Name
Toronto Western Hospital
City
Toronto
State/Province
Ontario
ZIP/Postal Code
M5T 2S8
Country
Canada
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Julian Kwok
Phone
1 416 603 580
Ext
2708
Email
julian.kwok@uhn.ca

12. IPD Sharing Statement

Plan to Share IPD
No

Learn more about this trial

Investigating LFP Correlates of TUS in Patients With Movement Disorders

We'll reach out to this number within 24 hrs