<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/NCT03253991</url>
  </required_header>
  <id_info>
    <org_study_id>ET002J</org_study_id>
    <nct_id>NCT03253991</nct_id>
  </id_info>
  <brief_title>A Study to Evaluate the Effectiveness and Safety of ExAblate MRgFUS on Essential Tremor</brief_title>
  <official_title>A Study to Evaluate the Effectiveness and Safety of ExAblate Transcranial MRgFUS Thalamotomy Treatment of Medication Refractory Essential Tremor Subjects</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>InSightec</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>InSightec</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      A Study to Evaluate the Effectiveness and Safety of ExAblate Transcranial MRgFUS Thalamotomy&#xD;
      Treatment of Medication Refractory Essential Tremor Subjects&#xD;
&#xD;
      The objective of this prospective, single-arm study is to test the efficacy of treatment&#xD;
      using the ExAblate Transcranial System and to further demonstrate safety in&#xD;
      medication-refractory tremor inpatients with essential tremor (ET).&#xD;
&#xD;
      The Indications for Use claim for this system is as follows: Treatment of&#xD;
      medication-refractory tremor in patients with essential tremor.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The objective of this prospective, multi-site, single-arm study is to test the efficacy of&#xD;
      treatment using the ExAblate Transcranial System and to further demonstrate safety in&#xD;
      medication-refractory tremor in subjects with essential tremor (ET).&#xD;
&#xD;
      Safety: To evaluate the incidence and severity of adverse events (AE/AEs) associated with&#xD;
      ExAblate Transcranial MRgFUS treatment of medication-refractory ET Effectiveness: To&#xD;
      determine the effectiveness of the ExAblate Transcranial MRgFUS treatment of&#xD;
      medication-refractory tremor (i.e. ET). Efficacy will be determined utilizing the Clinical&#xD;
      Rating Scale for Tremor (CRST) in ET from examinations at baseline and 3-Months post-ExAblate&#xD;
      treatment.&#xD;
&#xD;
      • This study is designed as a prospective, multi-site, single-arm study. Assessments of&#xD;
      primary efficacy endpoints will compare the three months after ExAblate treatment to Baseline&#xD;
      measurements for clinical symptom relief. Safety of ExAblate in the treatment of ET will be&#xD;
      collected for one year after ExAblate treatment. Relative Safety will be evaluated using a&#xD;
      common description of Significant Clinical Complications for patients treated in this study.&#xD;
      This study will be performed on the 3T MR scanners.&#xD;
&#xD;
      The secondary endpoints of the study are as follows:&#xD;
&#xD;
        1. Quality life claims: Questionnaire for Essential Tremor (QUEST) outcome (upper extremity&#xD;
           questions) at Months 3 change from Baseline&#xD;
&#xD;
        2. Durability (as measured by QUEST upper arm extremity questions) of the procedure as&#xD;
           reflected by the efficacy data through change from baseline measures through Month 12&#xD;
           follow up&#xD;
&#xD;
        3. Subject daily functionalities: as measured by CRST Part-C (subscales)Month 12 as&#xD;
           compared to Baseline.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Sponsor decision&#xD;
  </why_stopped>
  <start_date type="Actual">November 17, 2014</start_date>
  <completion_date type="Actual">February 2, 2023</completion_date>
  <primary_completion_date type="Actual">February 2, 2023</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>
    <intervention_model_description>Prospective multi-site, single-arm study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Safety - Will be determined evaluating incidence and severity of device related complications from first treatment day visit through all follow ups. Relative Safety will be evaluated describing Significant Clinical Complications for patients treated.</measure>
    <time_frame>1 year</time_frame>
    <description>All AEs will be reported and categorized by investigators as definitely, probably, possibly, or unrelated to the device or procedure and categorized by treatment group / treatment arm. Relative Safety will be evaluated using a common description of Significant Clinical Complications for patients treated in this study.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Effectiveness - Will be evaluated using the Clinical Rating Scale for Tremors (CRST) for ET subjects. Comparison will be performed from examinations at baseline and 3-Months post-ExAblate treatment.</measure>
    <time_frame>5 Years</time_frame>
    <description>Assessments of efficacy endpoints will compare the three months after ExAblate treatment to Baseline measurements for clinical symptom relief.</description>
  </primary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">154</enrollment>
  <condition>Essential Tremor</condition>
  <arm_group>
    <arm_group_label>MRgFUS treatment</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>MRgFUS device treatment, thalamotomy</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>MRgFUS treatment</intervention_name>
    <description>ExAblate Transcranial MRgFUS Thalamotomy Treatment of Medication Refractory Essential Tremor Subjects</description>
    <arm_group_label>MRgFUS treatment</arm_group_label>
    <other_name>Thalamotomy</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria&#xD;
&#xD;
          -  Men and women age 22 years or older&#xD;
&#xD;
          -  A diagnosis of ET as confirmed from clinical history and examination by a neurologist&#xD;
             or neurosurgeon specialized in movement disorder&#xD;
&#xD;
          -  Have had an inadequate response to one or two oral doses of medication, per local&#xD;
             standards. An inadequate medication trial is defined as a therapeutic dose of each&#xD;
             medication and poor response to drug, or the development of side effects as the&#xD;
             medication dose is titrated.&#xD;
&#xD;
          -  Able to communicate sensations during the ExAblate TcMRgFUS treatment&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Subjects with unstable cardiac status&#xD;
&#xD;
          -  Severe hypertension (diastolic BP &gt; 100 on medication)&#xD;
&#xD;
          -  Subjects with standard contraindications for MR imaging such as non-MRI compatible&#xD;
             implanted metallic devices including cardiac pacemakers, size limitations, etc.&#xD;
&#xD;
          -  Known intolerance or allergies to the MRI contrast agent (e.g. Gadolinium or&#xD;
             Magnevist) including advanced kidney disease&#xD;
&#xD;
          -  Patient with severely impaired renal function&#xD;
&#xD;
          -  History of abnormal bleeding and/or coagulopathy&#xD;
&#xD;
          -  History of immunocompromise including those who are HIV positive.&#xD;
&#xD;
          -  History of intracranial hemorrhage&#xD;
&#xD;
          -  Cerebrovascular disease (multiple CVA or CVA within 6 months)&#xD;
&#xD;
          -  Subjects with uncontrolled symptoms and signs of increased intracranial pressure&#xD;
             (e.g., headache, nausea, vomiting, lethargy, papilledema).&#xD;
&#xD;
          -  Individuals who are not able or willing to tolerate the required prolonged stationary&#xD;
             supine position during treatment (can be up to 4 hrs of total table time.)&#xD;
&#xD;
          -  Are participating or have participated in another clinical trial in the last 30 days&#xD;
&#xD;
          -  Significant claustrophobia that cannot be managed with mild medication.&#xD;
&#xD;
          -  Presence of any other neurodegenerative disease such as Parkinson-plus syndromes&#xD;
             suspected on neurological examination.&#xD;
&#xD;
          -  Presence of significant cognitive impairment&#xD;
&#xD;
          -  Subjects with life-threatening systemic disease&#xD;
&#xD;
          -  Subjects with a history of seizures within the past year&#xD;
&#xD;
          -  Subjects with presence or history of psychosis&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>22 Years</minimum_age>
    <maximum_age>99 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Chinese PLA General Hospital</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100853</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Henan Provincial People's Hospital</name>
      <address>
        <city>Zhengzhou</city>
        <state>Henan</state>
        <zip>450003</zip>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Sadamoto Hospital</name>
      <address>
        <city>Ehime</city>
        <zip>790-0052</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Shonan Fujisawa Tokushukai Hospital</name>
      <address>
        <city>Fujisawa</city>
        <zip>2510041</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hokkaido Ohno Memorial Hospital</name>
      <address>
        <city>Hokkaido</city>
        <zip>063-0052</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Hokuto</name>
      <address>
        <city>Hokkaido</city>
        <zip>080-0833</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Ohanishi Noerological Center</name>
      <address>
        <city>Hyōgo</city>
        <zip>6740064</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kumagaya General Hospital</name>
      <address>
        <city>Kumagaya</city>
        <zip>360-8567</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Department of Neurosurgery, Osaka University Hospital</name>
      <address>
        <city>Osaka</city>
        <zip>565-0871</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Tokyo Women's Medical University Hospital</name>
      <address>
        <city>Tokyo</city>
        <zip>62-8666</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Chang Bing Show Chwan Memorial Hospital</name>
      <address>
        <city>Chang Hua</city>
        <zip>505</zip>
        <country>Taiwan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
    <country>Japan</country>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>April 2023</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>August 15, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 18, 2017</study_first_posted>
  <last_update_submitted>April 19, 2023</last_update_submitted>
  <last_update_submitted_qc>April 19, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">April 20, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <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>
  <!-- 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/NCT03253991
org study id: ET002J
nct id: NCT03253991
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
A Study to Evaluate the Effectiveness and Safety of ExAblate Transcranial MRgFUS Thalamotomy
      Treatment of Medication Refractory Essential Tremor Subjects

      The objective of this prospective, single-arm study is to test the efficacy of treatment
      using the ExAblate Transcranial System and to further demonstrate safety in
      medication-refractory tremor inpatients with essential tremor (ET).

      The Indications for Use claim for this system is as follows: Treatment of
      medication-refractory tremor in patients with essential tremor.
The objective of this prospective, multi-site, single-arm study is to test the efficacy of
      treatment using the ExAblate Transcranial System and to further demonstrate safety in
      medication-refractory tremor in subjects with essential tremor (ET).

      Safety: To evaluate the incidence and severity of adverse events (AE/AEs) associated with
      ExAblate Transcranial MRgFUS treatment of medication-refractory ET Effectiveness: To
      determine the effectiveness of the ExAblate Transcranial MRgFUS treatment of
      medication-refractory tremor (i.e. ET). Efficacy will be determined utilizing the Clinical
      Rating Scale for Tremor (CRST) in ET from examinations at baseline and 3-Months post-ExAblate
      treatment.

      • This study is designed as a prospective, multi-site, single-arm study. Assessments of
      primary efficacy endpoints will compare the three months after ExAblate treatment to Baseline
      measurements for clinical symptom relief. Safety of ExAblate in the treatment of ET will be
      collected for one year after ExAblate treatment. Relative Safety will be evaluated using a
      common description of Significant Clinical Complications for patients treated in this study.
      This study will be performed on the 3T MR scanners.

      The secondary endpoints of the study are as follows:

        1. Quality life claims: Questionnaire for Essential Tremor (QUEST) outcome (upper extremity
           questions) at Months 3 change from Baseline

        2. Durability (as measured by QUEST upper arm extremity questions) of the procedure as
           reflected by the efficacy data through change from baseline measures through Month 12
           follow up

        3. Subject daily functionalities: as measured by CRST Part-C (subscales)Month 12 as
           compared to Baseline.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: Prospective multi-site, single-arm study
primary purpose: Treatment
masking: None (Open Label)
measure: Safety - Will be determined evaluating incidence and severity of device related complications from first treatment day visit through all follow ups. Relative Safety will be evaluated describing Significant Clinical Complications for patients treated.
time frame: 1 year
description: All AEs will be reported and categorized by investigators as definitely, probably, possibly, or unrelated to the device or procedure and categorized by treatment group / treatment arm. Relative Safety will be evaluated using a common description of Significant Clinical Complications for patients treated in this study.
measure: Effectiveness - Will be evaluated using the Clinical Rating Scale for Tremors (CRST) for ET subjects. Comparison will be performed from examinations at baseline and 3-Months post-ExAblate treatment.
time frame: 5 Years
description: Assessments of efficacy endpoints will compare the three months after ExAblate treatment to Baseline measurements for clinical symptom relief.
arm group label: MRgFUS treatment
arm group type: Experimental
description: MRgFUS device treatment, thalamotomy
intervention type: Device
intervention name: MRgFUS treatment
description: ExAblate Transcranial MRgFUS Thalamotomy Treatment of Medication Refractory Essential Tremor Subjects
arm group label: MRgFUS treatment
other name: Thalamotomy
criteria: 
gender: All
minimum age: 22 Years
maximum age: 99 Years
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: China
country: Japan
country: Taiwan
responsible party type: Sponsor
mesh term: Tremor
mesh term: Essential Tremor