<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/NCT04501484</url>
  </required_header>
  <id_info>
    <org_study_id>20-5172</org_study_id>
    <nct_id>NCT04501484</nct_id>
  </id_info>
  <brief_title>Bilateral Essential Tremor Treatment With FUS</brief_title>
  <acronym>BEST-FUS</acronym>
  <official_title>Bilateral Essential Tremor Treatment With Magnetic Resonance-guided Focused Ultrasound</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Health Network, Toronto</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Université de Sherbrooke</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>University Health Network, Toronto</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Combined Phase II/III, multi-center, prospective, single-blinded trial.&#xD;
&#xD;
      Ten (10) patients with who previously underwent successful and uncomplicated MRgFUS&#xD;
      thalamotomy for essential tremor will undergo a contralateral treatment. The incidence of&#xD;
      side effects will be determined at 1 and 3 months postoperatively, graded per the CTCAE v5&#xD;
      and analyzed by a data safety monitoring board. Upon successful review, this Phase II trial&#xD;
      will be converted to a Phase III trial of utility that will enrol 40 additional patients. The&#xD;
      primary outcome will be the change in QUEST score at 12 months postoperatively, as well as a&#xD;
      patient-reported assessment of Health Utility. Secondary outcomes will include objective&#xD;
      tremor, gait and speech assessments (filmed and scored by blinded evaluators), as well as&#xD;
      quality of life questionnaires and adverse events questionnaires. Outcomes will be assessed&#xD;
      immediately after the procedure, as well as 1, 3, 12, 24 and 36 months post-operatively.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">July 8, 2020</start_date>
  <completion_date type="Anticipated">October 2024</completion_date>
  <primary_completion_date type="Anticipated">October 2024</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
    <masking_description>All assessments filmed on video and scored by a blinded evaluator.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Change in QUEST Score</measure>
    <time_frame>12 months</time_frame>
    <description>Difference in QUEST score between baseline and the 12-month follow-up, with statistical significance defined as p = 0.05 and a minimum clinically important difference (MCID) defined as 5</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Patient-based Assessment of Utility</measure>
    <time_frame>12 months</time_frame>
    <description>A patient-reported assessment of utility after 12 months using the question &quot;Knowing what you know now, would you do this treatment again?&quot;.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Gait Assessment (NRS-11)</measure>
    <time_frame>Immediately after surgery, post operative month 1, 3, 12, 24, 36</time_frame>
    <description>Patient-reported and blinded observer rating of the patient's ability to walk (Numerical rating scale (NRS-11) from 0 to 10, with 10 being best)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gait Assessment (missteps)</measure>
    <time_frame>Immediately after surgery, post operative month 1, 3, 12, 24, 36</time_frame>
    <description>Number of missteps in a 6 m standardized tandem walk</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Falls</measure>
    <time_frame>Post operative month 1, 3, 12, 24, 36</time_frame>
    <description>Number of falls in last month</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Speech Assessment (NRS-11)</measure>
    <time_frame>Immediately after surgery, post operative month 1, 3, 12, 24, 36</time_frame>
    <description>Patient-reported and blinded observer rating of the patient's ability to speak (Numerical rating scale (NRS-11) from 0 to 10, with 10 being best)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Numbness</measure>
    <time_frame>Immediately after surgery, post operative month 1, 3, 12, 24, 36</time_frame>
    <description>Incidence of new-onset numbness</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Dysgeusia</measure>
    <time_frame>Immediately after surgery, post operative month 1, 3, 12, 24, 36</time_frame>
    <description>Incidence of taste alterations</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Other adverse events</measure>
    <time_frame>Immediately after surgery, post operative month 1, 3, 12, 24, 36</time_frame>
    <description>Incidence of other adverse events as classified in the CTCAE</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Tremor (CRST)</measure>
    <time_frame>Immediately after surgery, post operative month 1, 3, 12, 24, 36</time_frame>
    <description>Assessment of tremor using the Clinical Rating Scale for Tremor (CRST) parts A (0-88) and B (0-36), higher scores correspond to a worse tremor).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life (QUEST)</measure>
    <time_frame>Post operative month 1, 3, 12, 24, 36</time_frame>
    <description>QUality of life in ESsential Tremor (QUEST) questionnaire (0-100%, higher scores correspond to a worse quality of life)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of life (CRST part C)</measure>
    <time_frame>Post operative month 1, 3, 12, 24, 36</time_frame>
    <description>Part C of the Clinical Rating Scale for Tremor (CRST) (0-32, higher scores correspond to a worse quality of life)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Health Utility (EQ-5D-5L)</measure>
    <time_frame>Post operative month 1, 3, 12, 24, 36</time_frame>
    <description>Health Utility measured using the EQ-5D-5L and computed using the Canadian preference weights. Values range from 0 to 1, with 1 representing a perfect health.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">50</enrollment>
  <condition>Essential Tremor</condition>
  <arm_group>
    <arm_group_label>Treatment Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will undergo a thalamotomy contralateral to their previous treatment with MRgFUS using ExAblate Neuro 4000 device (InSightec Ltd, Tirat Carmel, Israel).</description>
  </arm_group>
  <intervention>
    <intervention_type>Procedure</intervention_type>
    <intervention_name>Magnetic Resonance-guided Focused Ultrasound VIM Thalamotomy</intervention_name>
    <description>Ablation of contralateral VIM nucleus of thalamus with MRgFUS using ExAblate Neuro 4000 Device (InSightec Ltd, Tirat Carmel, Israel)</description>
    <arm_group_label>Treatment Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Patients must be ≥ 18 years&#xD;
&#xD;
          -  The patient has a primary diagnosis of ET or ET plus confirmed by a movement disorder&#xD;
             neurologist;&#xD;
&#xD;
          -  The patient previously underwent a MRgFUS (&gt; 6 months ago);&#xD;
&#xD;
          -  The tremor on the untreated side negatively impacts the patients' quality of life;&#xD;
&#xD;
          -  The patient wants treatment of the contralateral side.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Clinically relevant gait and/or balance impairment (e.g. wide-based, more than 2&#xD;
             falls/months, wheelchair, walker, cane use)&#xD;
&#xD;
          -  Clinically relevant speech impairment (e.g. impairment of intelligibility)&#xD;
&#xD;
          -  Inability to comply with the follow-up schedule;&#xD;
&#xD;
          -  Refusal of the treating physician.&#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>Andres Lozano, MD, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Toronto</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Martha Lenis, BHA</last_name>
    <phone>+14166035800</phone>
    <phone_ext>2797</phone_ext>
    <email>martha.lenis@uhnresearch.ca</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Christian Iorio-Morin, MD, PhD</last_name>
    <email>christian.iorio-morin@usherbrooke.ca</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Toronto Western Hospital, University Health Network</name>
      <address>
        <city>Toronto</city>
        <state>Ontario</state>
        <zip>M5T 2S8</zip>
        <country>Canada</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Martha Lenis, BHA</last_name>
      <phone>+14166035800</phone>
      <phone_ext>2797</phone_ext>
      <email>martha.lenis@uhnresearch.ca</email>
    </contact>
  </location>
  <location_countries>
    <country>Canada</country>
  </location_countries>
  <verification_date>May 2022</verification_date>
  <study_first_submitted>July 29, 2020</study_first_submitted>
  <study_first_submitted_qc>August 3, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">August 6, 2020</study_first_posted>
  <last_update_submitted>May 16, 2022</last_update_submitted>
  <last_update_submitted_qc>May 16, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">May 17, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University Health Network, Toronto</investigator_affiliation>
    <investigator_full_name>Andres M. Lozano</investigator_full_name>
    <investigator_title>Neurosurgeon</investigator_title>
  </responsible_party>
  <keyword>High-Intensity Focused Ultrasound Ablation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Tremor</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>


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/NCT04501484
org study id: 20-5172
nct id: NCT04501484
lead sponsor: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
is us export: No
Combined Phase II/III, multi-center, prospective, single-blinded trial.

      Ten (10) patients with who previously underwent successful and uncomplicated MRgFUS
      thalamotomy for essential tremor will undergo a contralateral treatment. The incidence of
      side effects will be determined at 1 and 3 months postoperatively, graded per the CTCAE v5
      and analyzed by a data safety monitoring board. Upon successful review, this Phase II trial
      will be converted to a Phase III trial of utility that will enrol 40 additional patients. The
      primary outcome will be the change in QUEST score at 12 months postoperatively, as well as a
      patient-reported assessment of Health Utility. Secondary outcomes will include objective
      tremor, gait and speech assessments (filmed and scored by blinded evaluators), as well as
      quality of life questionnaires and adverse events questionnaires. Outcomes will be assessed
      immediately after the procedure, as well as 1, 3, 12, 24 and 36 months post-operatively.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
masking description: All assessments filmed on video and scored by a blinded evaluator.
measure: Change in QUEST Score
time frame: 12 months
description: Difference in QUEST score between baseline and the 12-month follow-up, with statistical significance defined as p = 0.05 and a minimum clinically important difference (MCID) defined as 5
measure: Patient-based Assessment of Utility
time frame: 12 months
description: A patient-reported assessment of utility after 12 months using the question "Knowing what you know now, would you do this treatment again?".
measure: Gait Assessment (NRS-11)
time frame: Immediately after surgery, post operative month 1, 3, 12, 24, 36
description: Patient-reported and blinded observer rating of the patient's ability to walk (Numerical rating scale (NRS-11) from 0 to 10, with 10 being best)
measure: Gait Assessment (missteps)
time frame: Immediately after surgery, post operative month 1, 3, 12, 24, 36
description: Number of missteps in a 6 m standardized tandem walk
measure: Falls
time frame: Post operative month 1, 3, 12, 24, 36
description: Number of falls in last month
measure: Speech Assessment (NRS-11)
time frame: Immediately after surgery, post operative month 1, 3, 12, 24, 36
description: Patient-reported and blinded observer rating of the patient's ability to speak (Numerical rating scale (NRS-11) from 0 to 10, with 10 being best)
measure: Numbness
time frame: Immediately after surgery, post operative month 1, 3, 12, 24, 36
description: Incidence of new-onset numbness
measure: Dysgeusia
time frame: Immediately after surgery, post operative month 1, 3, 12, 24, 36
description: Incidence of taste alterations
measure: Other adverse events
time frame: Immediately after surgery, post operative month 1, 3, 12, 24, 36
description: Incidence of other adverse events as classified in the CTCAE
measure: Tremor (CRST)
time frame: Immediately after surgery, post operative month 1, 3, 12, 24, 36
description: Assessment of tremor using the Clinical Rating Scale for Tremor (CRST) parts A (0-88) and B (0-36), higher scores correspond to a worse tremor).
measure: Quality of life (QUEST)
time frame: Post operative month 1, 3, 12, 24, 36
description: QUality of life in ESsential Tremor (QUEST) questionnaire (0-100%, higher scores correspond to a worse quality of life)
measure: Quality of life (CRST part C)
time frame: Post operative month 1, 3, 12, 24, 36
description: Part C of the Clinical Rating Scale for Tremor (CRST) (0-32, higher scores correspond to a worse quality of life)
measure: Health Utility (EQ-5D-5L)
time frame: Post operative month 1, 3, 12, 24, 36
description: Health Utility measured using the EQ-5D-5L and computed using the Canadian preference weights. Values range from 0 to 1, with 1 representing a perfect health.
arm group label: Treatment Group
arm group type: Experimental
description: Participants will undergo a thalamotomy contralateral to their previous treatment with MRgFUS using ExAblate Neuro 4000 device (InSightec Ltd, Tirat Carmel, Israel).
intervention type: Procedure
intervention name: Magnetic Resonance-guided Focused Ultrasound VIM Thalamotomy
description: Ablation of contralateral VIM nucleus of thalamus with MRgFUS using ExAblate Neuro 4000 Device (InSightec Ltd, Tirat Carmel, Israel)
arm group label: Treatment Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Andres Lozano, MD, PhD
role: Principal Investigator
affiliation: University of Toronto
last name: Martha Lenis, BHA
phone: +14166035800
phone ext: 2797
email: martha.lenis@uhnresearch.ca
last name: Christian Iorio-Morin, MD, PhD
email: christian.iorio-morin@usherbrooke.ca
facility: 
status: Recruiting
contact: 
country: Canada
responsible party type: Principal Investigator
investigator affiliation: University Health Network, Toronto
investigator full name: Andres M. Lozano
investigator title: Neurosurgeon
mesh term: Tremor
mesh term: Essential Tremor
sharing ipd: No