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

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ClinicalTrials.gov Identifier: NCT05965960
Recruitment Status : Recruiting
First Posted : July 28, 2023
Last Update Posted : October 10, 2023
Sponsor:
Information provided by (Responsible Party):
University Health Network, Toronto

Tracking Information
First Submitted Date  ICMJE June 7, 2023
First Posted Date  ICMJE July 28, 2023
Last Update Posted Date October 10, 2023
Actual Study Start Date  ICMJE May 18, 2023
Estimated Primary Completion Date June 1, 2024   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: July 25, 2023)
  • 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
  • Stimulation artifact (Experiment 2) [ Time Frame: Online during sonications ]
    Presence of a stimulation artifact during LFP recordings
Original Primary Outcome Measures  ICMJE Same as current
Change History
Current Secondary Outcome Measures  ICMJE
 (submitted: July 25, 2023)
  • 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
  • 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
  • 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
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Investigating LFP Correlates of TUS in Patients With Movement Disorders
Official Title  ICMJE Investigating Local Field Potential Correlates of Transcranial Ultrasound Stimulation in Patients With Movement Disorders
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.
Study Type  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Participant, Outcomes 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.
Primary Purpose: Basic Science
Condition  ICMJE
  • Parkinson Disease
  • Essential Tremor
  • Dystonia
Intervention  ICMJE
  • 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
  • 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
Study Arms  ICMJE
  • 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
    Intervention: Device: TUS Active
  • 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
    Intervention: Device: TUS Sham
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Recruiting
Estimated Enrollment  ICMJE
 (submitted: July 25, 2023)		 25
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE June 1, 2024
Estimated Primary Completion Date June 1, 2024   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE
Contact: Julian Kwok 1 416 603 5800 ext 2708 julian.kwok@uhn.ca
Contact: Can Sarica, MD 1 437 777 2269 can.sarica@mail.utoronto.ca
Listed Location Countries  ICMJE Canada
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT05965960
Other Study ID Numbers  ICMJE 20-5740#2
Has Data Monitoring Committee No
U.S. FDA-regulated Product
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Current Responsible Party University Health Network, Toronto
Original Responsible Party Robert Chen, University Health Network, Toronto, Senior Scientist
Current Study Sponsor  ICMJE University Health Network, Toronto
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Not Provided
Investigators  ICMJE
Principal Investigator: Robert Chen, MBBS University Health Network, Toronto
PRS Account University Health Network, Toronto
Verification Date July 2023

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP