xml: <clinical_study>
    <!-- This xml conforms to an XML Schema at:
      https://clinicaltrials.gov/ct2/html/images/info/public.xsd -->
    <required_header>
      <download_date>ClinicalTrials.gov processed this data on September 20, 2023</download_date>
      <link_text>Link to the current ClinicalTrials.gov record.</link_text>
      <url>https://clinicaltrials.gov/ct2/show/NCT05965960</url>
    </required_header>
    <id_info>
      <org_study_id>20-5740#2</org_study_id>
      <nct_id>NCT05965960</nct_id>
    </id_info>
    <brief_title>Investigating LFP Correlates of TUS in Patients With Movement Disorders</brief_title>
    <acronym>TUS-LFP</acronym>
    <official_title>Investigating Local Field Potential Correlates of Transcranial Ultrasound Stimulation in Patients With Movement Disorders</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University Health Network, Toronto</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University Health Network, Toronto</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        Transcranial Ultrasound Stimulation (TUS) is an emerging non-invasive brain stimulation(NIBS)&#xD;
        technique that can be used on both superficial and deep brain targets with a high spatial&#xD;
        resolution as small as a few cubic millimeters. Neural correlates of TUS have yet been&#xD;
        elucidated. To date, no intracranial recordings (i.e., local field potential [LFP]) have been&#xD;
        captured during or after TUS in patients with movement disorders. In this study, we are&#xD;
        aiming to profile basal ganglia LFP activity during and after TUS by using a DBS system that&#xD;
        is capable of recording LFP. This can shed light on mechanisms of TUS, as well as allow&#xD;
        identification of a neurophysiological biomarker that can be used to tune the TUS sonication&#xD;
        parameters for future clinical trials.&#xD;
      </textblock>
    </brief_summary>
    <detailed_description>
      <textblock>
        Experiment 1: Subjects will be randomly assigned to either the sham or active stimulation&#xD;
        group during the first study visit. In the second study visit, there will be a crossover&#xD;
        between the groups, with all subjects undergoing one sham and one active stimulation visit&#xD;
        before the study is completed. During the active stimulation visit, a theta burst protocol&#xD;
        (Isppa: 30 W/cm2, burst length: 20 ms, period: 200 ms, focus: 35 mm, frequency 500 kHz) will&#xD;
        be used to sonicate the bilateral primary motor cortices (M1) for 2 minutes. The sham group&#xD;
        involves sonications performed with the power set to 0 watts over bilateral M1s. In both&#xD;
        groups, the subjects will be masked using white noise transmitted through earbuds. The&#xD;
        cortical targets will be identified anatomically using structural MRIs and a neuronavigation&#xD;
        system.&#xD;
  &#xD;
        The Percept PC DBS system will be used to record local field potentials (LFPs) from the&#xD;
        subthalamic nucleus (STN) or globus pallidus internus (GPI) at various time points: before&#xD;
        (baseline) and during the sonications, as well as at 10-, 30-, and 45-minute intervals after&#xD;
        the sonications. These recordings will be obtained while the subjects engage in a finger&#xD;
        tapping task monitored by an accelerometer, as well as during resting periods. The power of&#xD;
        LFPs across different frequencies will be compared and correlated with the velocity observed&#xD;
        during the finger tapping task.&#xD;
  &#xD;
        Following the completion of sham and active stimulation visits, the subjects will have the&#xD;
        opportunity to participate in an optional control group visit, which entails sonication of&#xD;
        the occipital cortex utilizing the theta burst protocol.&#xD;
  &#xD;
        Experiment 2: TUS will be utilized to target the area directly over the DBS lead, while&#xD;
        concurrently recording LFPs to identify any stimulation artifact indicative of target&#xD;
        area-sonication engagement.&#xD;
      </textblock>
    </detailed_description>
    <overall_status>Recruiting</overall_status>
    <start_date type="Actual">May 18, 2023</start_date>
    <completion_date type="Anticipated">June 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">June 1, 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Crossover Assignment</intervention_model>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Double (Participant, Outcomes Assessor)</masking>
      <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.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>LFP power (Experiment 1)</measure>
      <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</time_frame>
      <description>The change of power of LFPs across different frequencies</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Stimulation artifact (Experiment 2)</measure>
      <time_frame>Online during sonications</time_frame>
      <description>Presence of a stimulation artifact during LFP recordings</description>
    </primary_outcome>
    <secondary_outcome>
      <measure>UPDRS (Experiment 1)</measure>
      <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).</time_frame>
      <description>Change of UPDRS score</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Finger tapping task (Experiment 1)</measure>
      <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</time_frame>
      <description>Correlation of LFP power change with the velocity change during finger tapping task as recorded by an accelerometer</description>
    </secondary_outcome>
    <secondary_outcome>
      <measure>Adverse effect profile (Experiment 1 and 2)</measure>
      <time_frame>From the initiation of the study up to 1 day after its completion.</time_frame>
      <description>Presence of adverse effects as reported subjectively by the patient</description>
    </secondary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">25</enrollment>
    <condition>Parkinson Disease</condition>
    <condition>Essential Tremor</condition>
    <condition>Dystonia</condition>
    <arm_group>
      <arm_group_label>Active Low Intensity Transcranial Focused Ultrasound</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>NeuroFUS device stimulation with 4 channel transducer Stimulation target = M1 Stimulation parameters = Theta burst protocol and 30 Watts</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Sham Low Intensity Transcranial Focused Ultrasound</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
      <description>NeuroFUS device stimulation with 4 channel transducer Stimulation target = M1 Stimulation parameters = Theta burst protocol and 0 Watts</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>TUS Active</intervention_name>
      <description>Bilateral M1s will be sonicated using NeuroFUS device for two minutes per hemisphere with theta burst protocol and 30 W/cm2 Isppa</description>
      <arm_group_label>Active Low Intensity Transcranial Focused Ultrasound</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>TUS Sham</intervention_name>
      <description>Bilateral M1s will be sonicated using NeuroFUS device for two minutes per hemisphere with theta burst protocol and 0 W/cm2 Isppa</description>
      <arm_group_label>Sham Low Intensity Transcranial Focused Ultrasound</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Adult patients with movement disorders (diagnosed by a movement disorder specialist)&#xD;
  &#xD;
            2. Implantation of a Percept PC DBS system at least one month before the sonications&#xD;
  &#xD;
            3. Stable dopaminergic medication dose for a minimum of 4 weeks&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Concomitant neurological conditions (stroke, seizure, dementia, major depression /&#xD;
               psychiatric disorders, active drug abuse/addiction and major&#xD;
               neuromuscular/musculoskeletal diseases)&#xD;
  &#xD;
            2. Declined cognitive scores (MoCA score &lt; 22)&#xD;
  &#xD;
            3. Implants (cardiac pacemaker, implantable cardioverter-defibrillator, intracranial&#xD;
               devices other than DBS system such as shunts and MR-unsafe devices)&#xD;
  &#xD;
            4. History of intracranial lesioning procedures&#xD;
  &#xD;
            5. Major systemic illness, infection or pregnancy&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>N/A</maximum_age>
      <healthy_volunteers>No</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Robert Chen, MBBS</last_name>
      <role>Principal Investigator</role>
      <affiliation>University Health Network, Toronto</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Julian Kwok</last_name>
      <phone>1 416 603 5800</phone>
      <phone_ext>2708</phone_ext>
      <email>julian.kwok@uhn.ca</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Can Sarica, MD</last_name>
      <phone>1 437 777 2269</phone>
      <email>can.sarica@mail.utoronto.ca</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Toronto Western Hospital</name>
        <address>
          <city>Toronto</city>
          <state>Ontario</state>
          <zip>M5T 2S8</zip>
          <country>Canada</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Julian Kwok</last_name>
        <phone>1 416 603 580</phone>
        <phone_ext>2708</phone_ext>
        <email>julian.kwok@uhn.ca</email>
      </contact>
    </location>
    <location_countries>
      <country>Canada</country>
    </location_countries>
    <verification_date>July 2023</verification_date>
    <study_first_submitted>June 7, 2023</study_first_submitted>
    <study_first_submitted_qc>July 25, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">July 28, 2023</study_first_posted>
    <last_update_submitted>July 25, 2023</last_update_submitted>
    <last_update_submitted_qc>July 25, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">July 28, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Principal Investigator</responsible_party_type>
      <investigator_affiliation>University Health Network, Toronto</investigator_affiliation>
      <investigator_full_name>Robert Chen</investigator_full_name>
      <investigator_title>Senior Scientist</investigator_title>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Parkinson Disease</mesh_term>
      <mesh_term>Dystonia</mesh_term>
      <mesh_term>Movement Disorders</mesh_term>
      <mesh_term>Essential Tremor</mesh_term>
    </condition_browse>
    <patient_data>
      <sharing_ipd>No</sharing_ipd>
    </patient_data>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: download date: ClinicalTrials.gov processed this data on September 20, 2023
  link text: Link to the current ClinicalTrials.gov record.
  url: https://clinicaltrials.gov/ct2/show/NCT05965960
  org study id: 20-5740#2
  nct id: NCT05965960
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  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.
  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.
  allocation: Randomized
  intervention model: Crossover Assignment
  primary purpose: Basic Science
  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.
  measure: 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
  description: The change of power of LFPs across different frequencies
  measure: Stimulation artifact (Experiment 2)
  time frame: Online during sonications
  description: Presence of a stimulation artifact during LFP recordings
  measure: 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).
  description: Change of UPDRS score
  measure: 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
  description: Correlation of LFP power change with the velocity change during finger tapping task as recorded by an accelerometer
  measure: Adverse effect profile (Experiment 1 and 2)
  time frame: From the initiation of the study up to 1 day after its completion.
  description: Presence of adverse effects as reported subjectively by the patient
  arm group label: Active Low Intensity Transcranial Focused Ultrasound
  arm group type: Active Comparator
  description: NeuroFUS device stimulation with 4 channel transducer Stimulation target = M1 Stimulation parameters = Theta burst protocol and 30 Watts
  arm group label: Sham Low Intensity Transcranial Focused Ultrasound
  arm group type: Sham Comparator
  description: NeuroFUS device stimulation with 4 channel transducer Stimulation target = M1 Stimulation parameters = Theta burst protocol and 0 Watts
  intervention type: Device
  intervention name: TUS Active
  description: Bilateral M1s will be sonicated using NeuroFUS device for two minutes per hemisphere with theta burst protocol and 30 W/cm2 Isppa
  arm group label: Active Low Intensity Transcranial Focused Ultrasound
  intervention type: Device
  intervention name: TUS Sham
  description: Bilateral M1s will be sonicated using NeuroFUS device for two minutes per hemisphere with theta burst protocol and 0 W/cm2 Isppa
  arm group label: Sham Low Intensity Transcranial Focused Ultrasound
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: N/A
  healthy volunteers: No
  last name: Robert Chen, MBBS
  role: Principal Investigator
  affiliation: University Health Network, Toronto
  last name: Julian Kwok
  phone: 1 416 603 5800
  phone ext: 2708
  email: julian.kwok@uhn.ca
  last name: Can Sarica, MD
  phone: 1 437 777 2269
  email: can.sarica@mail.utoronto.ca
  facility: 
  status: Recruiting
  contact: 
  country: Canada
  responsible party type: Principal Investigator
  investigator affiliation: University Health Network, Toronto
  investigator full name: Robert Chen
  investigator title: Senior Scientist
  mesh term: Parkinson Disease
  mesh term: Dystonia
  mesh term: Movement Disorders
  mesh term: Essential Tremor
  sharing ipd: No