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History of Changes for Study: NCT05965960
Investigating LFP Correlates of TUS in Patients With Movement Disorders (TUS-LFP)
Latest version (submitted October 6, 2023) on ClinicalTrials.gov
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Study Record Versions
Version A B Submitted Date Changes
1 July 25, 2023 None (earliest Version on record)
2 October 6, 2023 Sponsor/Collaborators, Arms and Interventions, Study Description and Study Status
Comparison Format:
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Study NCT05965960
Submitted Date:  July 25, 2023 (v1)
Open or close this module Study Identification
Unique Protocol ID: 20-5740#2
Brief Title: Investigating LFP Correlates of TUS in Patients With Movement Disorders (TUS-LFP)
Official Title: Investigating Local Field Potential Correlates of Transcranial Ultrasound Stimulation in Patients With Movement Disorders
Secondary IDs:
Open or close this module Study Status
Record Verification: July 2023
Overall Status: Recruiting
Study Start: May 18, 2023
Primary Completion: June 1, 2024 [Anticipated]
Study Completion: June 1, 2024 [Anticipated]
First Submitted: June 7, 2023
First Submitted that
Met QC Criteria:		 July 25, 2023
First Posted: July 28, 2023 [Actual]
Last Update Submitted that
Met QC Criteria:		 July 25, 2023
Last Update Posted: July 28, 2023 [Actual]
Open or close this module Sponsor/Collaborators
Sponsor: University Health Network, Toronto
Responsible Party: Principal Investigator
Investigator: Robert Chen
Official Title: Senior Scientist
Affiliation: University Health Network, Toronto
Collaborators:
Open or close this module Oversight
U.S. FDA-regulated Drug: No
U.S. FDA-regulated Device: No
Data Monitoring: No
Open or close this module 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, focus: 35 mm, frequency 500 kHz) will be used to sonicate the bilateral primary motor cortices (M1) for 2 minutes. The sham group involves sonications performed with the power set to 0 watts over bilateral M1s. In both groups, the subjects will be masked using white noise transmitted through earbuds. The cortical 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.
Open or close this module Conditions
Conditions: Parkinson Disease
Essential Tremor
Dystonia
Keywords:
Open or close this module Study Design
Study Type: Interventional
Primary Purpose: Basic Science
Study Phase: Not Applicable
Interventional Study Model: Crossover Assignment
Number of Arms: 2
Masking: Double (Participant, Outcomes Assessor)
Allocation: Randomized
Enrollment: 25 [Anticipated]
Open or close this module Arms and Interventions
Arms Assigned Interventions
Active Comparator: Active Low Intensity Transcranial Focused Ultrasound
NeuroFUS device stimulation with 4 channel transducer Stimulation target = M1 Stimulation parameters = Theta burst protocol and 30 Watts
 Device: TUS Active
Bilateral M1s 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 Stimulation parameters = Theta burst protocol and 0 Watts
 Device: TUS Sham
Bilateral M1s will be sonicated using NeuroFUS device for two minutes per hemisphere with theta burst protocol and 0 W/cm2 Isppa
Open or close this module Outcome Measures
Primary Outcome Measures:
1. 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
2. Stimulation artifact (Experiment 2)
[ Time Frame: Online during sonications ]

Presence of a stimulation artifact during LFP recordings
Secondary Outcome Measures:
1. 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
2. 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
3. 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
Open or close this module Eligibility
Minimum Age: 18 Years
Maximum Age:
Sex: All
Gender Based:
Accepts Healthy Volunteers: No
Criteria:

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
Open or close this module Contacts/Locations
Central Contact Person: Julian Kwok
Telephone: 1 416 603 5800 Ext. 2708
Email: julian.kwok@uhn.ca
Central Contact Backup: Can Sarica, MD
Telephone: 1 437 777 2269
Email: can.sarica@mail.utoronto.ca
Study Officials: Robert Chen, MBBS
Principal Investigator
University Health Network, Toronto
Locations: Canada, Ontario
Toronto Western Hospital
[Recruiting]
Toronto, Ontario, Canada, M5T 2S8
Contact:Contact: Julian Kwok 1 416 603 580 Ext. 2708 julian.kwok@uhn.ca
Open or close this module IPDSharing
Plan to Share IPD: No
Open or close this module References
Citations:
Links:
Available IPD/Information:
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U.S. National Library of Medicine | U.S. National Institutes of Health | U.S. Department of Health & Human Services