Investigating LFP Correlates of TUS in Patients With Movement Disorders

Parkinson Disease Clinical Trial

— TUS-LFP  

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT05965960
• Other study ID #: 20-5740#2
• Status: Recruiting
• Phase: N/A
• Start date: May 18, 2023
• Est. completion date: June 1, 2024

Study information

• Verified date: July 2023
• Source: University Health Network, Toronto
• Contact: Julian Kwok
• Phone: 1 416 603 5800
• Email: julian.kwok[@]uhn.ca
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: June 1, 2024
• Est. primary completion date: June 1, 2024
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Dystonia
• Essential Tremor
• Movement Disorders
• Parkinson Disease

Intervention

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
• 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

Locations

Country	Name	City	State
Canada	Toronto Western Hospital	Toronto	Ontario

Sponsors (1)

Lead Sponsor	Collaborator
University Health Network, Toronto

Country where clinical trial is conducted

Canada, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	LFP power (Experiment 1)	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
Primary	Stimulation artifact (Experiment 2)	Presence of a stimulation artifact during LFP recordings	Online during sonications
Secondary	UPDRS (Experiment 1)	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).
Secondary	Finger tapping task (Experiment 1)	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
Secondary	Adverse effect profile (Experiment 1 and 2)	Presence of adverse effects as reported subjectively by the patient	From the initiation of the study up to 1 day after its completion.