<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/NCT01698450</url>
  </required_header>
  <id_info>
    <org_study_id>EK: 2012-0027</org_study_id>
    <nct_id>NCT01698450</nct_id>
  </id_info>
  <brief_title>Magnetic Resonance (MR) Guided Functional Ultrasound-Neurosurgery for Movement Disorders</brief_title>
  <official_title>MR-Guided Functional Ultrasound-Neurosurgery for Movement Disorders</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Children's Hospital, Zurich</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Children's Hospital, Zurich</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The aim of this study is to asses the efficacy and the clinical safety of the transcranial&#xD;
      magnetic resonance guided high intensity focused ultrasound system ExAblate 4000, InSightec&#xD;
      Ltd. for functional neurosurgery in the treatment of movement disorders. The treatments to be&#xD;
      conducted in this study are non-invasive, i.e. without opening the skull, and will create&#xD;
      microthalamotomies in specific target areas such as thalamus, subthalamus and pallidum. The&#xD;
      data obtained in this study will be used to evaluate the basic safety aspects of this new&#xD;
      treatment technology and will serve as a basis for the clinical introduction of MR-guided&#xD;
      ultrasound neurosurgery.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>November 2012</start_date>
  <completion_date type="Actual">December 2013</completion_date>
  <primary_completion_date type="Actual">December 2013</primary_completion_date>
  <phase>Phase 1</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>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Lesion Size</measure>
    <time_frame>3 months</time_frame>
    <description>Size of lesion in the target area for each sonication as a function of applied energy/temperature.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Patient Safety</measure>
    <time_frame>3 months</time_frame>
    <description>Number of Patients with Adverse Events as a Measure of Safety and Tolerability.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical efficacy and QOL</measure>
    <time_frame>3 months</time_frame>
    <description>Efficacy and QOL will be quantified on respective rating scales (specified in protocol).</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Essential Tremor</condition>
  <condition>Dystonia</condition>
  <condition>Parkinson's Disease</condition>
  <arm_group>
    <arm_group_label>Focused Ultrasound for Movement Disorders</arm_group_label>
    <arm_group_type>Other</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Non-invasive intervention with focused ultrasound (ExAblate 4000)</intervention_name>
    <description>Non-invasive brain intervention using MR-guided focused ultrasound</description>
    <arm_group_label>Focused Ultrasound for Movement Disorders</arm_group_label>
    <other_name>ExAblate 4000</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Men and women, between 18 and 80 years, inclusive.&#xD;
&#xD;
          -  Patients who are able and willing to give consent and able to attend all study visits.&#xD;
&#xD;
          -  A diagnosis of a MD, such as Essential Tremor (ET), Idiopathic Parkinson's diseases or&#xD;
             primary Dystonia as confirmed from clinical history and examination by a movement&#xD;
             disorder neurologist.&#xD;
&#xD;
          -  A MD refractory to adequate medical treatment, or in whom the indication for Deep&#xD;
             Brain Stimulation (DBS) would be given, but DBS cannot be performed because of medical&#xD;
             comorbidities or medical reasons, or because the patient clearly confirms by written&#xD;
             statement that he does not want to undergo DBS for personal reasons (PD: increasing&#xD;
             motor fluctuations albeit optimal medical treatment &amp; unbearable side effects of&#xD;
             medication; ET: failure of adequate tremor control with Propranolol and Primidone&#xD;
             alone and in combination; Dystonia: dystonia or pain not controlled by oral&#xD;
             medication). An adequate medication trial is defined as a therapeutic dose of each&#xD;
             medication or the development of side effects as the medication dose is titrated.&#xD;
&#xD;
          -  Either the medial thalamic nuclei or the subthalamic or pallidal areas can be target&#xD;
             by the ExAblate device. The target region must be apparent on MRI such that targeting&#xD;
             can be performed with either direct visualization or by measurement from landmarks,&#xD;
             using the &quot;Stereotactic Atlas of the Human Thalamus and Basal Ganglia&quot; by Anne Morel,&#xD;
             39 analogous to our first clinical FUS study on patients with chronic pain 33.&#xD;
&#xD;
          -  Able to communicate sensations during the ExAblate MRgFUS treatment&#xD;
&#xD;
          -  Stable doses of all medications for 30 days prior to study entry and for the duration&#xD;
             of the study.&#xD;
&#xD;
          -  Significant disability due to MD despite medical treatment (speaking, feeding other&#xD;
             than liquids, bringing liquids to mouth, hygiene, dressing, writing, working, and&#xD;
             social activities)&#xD;
&#xD;
          -  Inclusion and exclusion criteria have been agreed upon by two members of the medical&#xD;
             team.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Patients with unstable cardiac status including:&#xD;
&#xD;
               -  Unstable angina pectoris on medication&#xD;
&#xD;
               -  Patients with documented myocardial infarction within six months of protocol&#xD;
                  entry&#xD;
&#xD;
               -  Congestive heart failure requiring medication (other than diuretic)&#xD;
&#xD;
               -  Patients on anti-arrhythmic drugs&#xD;
&#xD;
          -  Patients exhibiting any behavior(s) consistent with ethanol or substance abuse as&#xD;
             defined by the criteria outlined in the DSM-IV as manifested by one (or more) of the&#xD;
             following occurring within a 12 month period:&#xD;
&#xD;
               -  Recurrent substance use resulting in a failure to fulfill major role obligations&#xD;
                  at work, school, or home (such as repeated absences or poor work performance&#xD;
                  related to substance use; substance-related absences, suspensions, or expulsions&#xD;
                  from school; or neglect of children or household).&#xD;
&#xD;
               -  Recurrent substance use in situations in which it is physically hazardous (such&#xD;
                  as driving an automobile or operating a machine when impaired by substance use)&#xD;
&#xD;
               -  Recurrent substance-related legal problems (such as arrests for substance related&#xD;
                  disorderly conduct)&#xD;
&#xD;
               -  Continued substance use despite having persistent or recurrent social or&#xD;
                  interpersonal problems caused or exacerbated by the effects of the substance (for&#xD;
                  example, arguments with spouse about consequences of intoxication and physical&#xD;
                  fights).&#xD;
&#xD;
          -  Severe hypertension (diastolic BP &gt; 100 on medication)&#xD;
&#xD;
          -  Patients 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) including&#xD;
             advanced kidney disease&#xD;
&#xD;
          -  Severely impaired renal function (estimated glomerular filtration rate &lt; 45ml/min/&#xD;
             1.73 m2) or receiving dialysis&#xD;
&#xD;
          -  History of abnormal bleeding and/or coagulopathy&#xD;
&#xD;
          -  Receiving anticoagulant (e.g. warfarin) or antiplatelet (e.g. aspirin) therapy within&#xD;
             one week of focused ultrasound procedure or drugs known to increase risk or hemorrhage&#xD;
             (e.g. Avastin) within one month of focused ultrasound procedure&#xD;
&#xD;
          -  Active or suspected acute or chronic uncontrolled infection&#xD;
&#xD;
          -  History of intracranial hemorrhage&#xD;
&#xD;
          -  Cerebrovascular disease (multiple CVA or CVA within 6 months)&#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;
          -  Symptoms and signs of increased intracranial pressure (e.g. headache, nausea,&#xD;
             vomiting, lethargy, and papilledema)&#xD;
&#xD;
          -  Participation in another clinical trial in the last 30 days&#xD;
&#xD;
          -  Patients unable to communicate with the investigator and staff.&#xD;
&#xD;
          -  Presence of any other neurodegenerative disease like Parkinson-plus syndromes&#xD;
             suspected on neurological examination. These include: multisystem atrophy, progressive&#xD;
             supranuclear palsy, dementia with Lewy bodies, and Alzheimer's disease.&#xD;
&#xD;
          -  Presence of significant cognitive impairment as determined with a score ≤ 24 on the&#xD;
             Mini Mental Status Examination (MMSE)&#xD;
&#xD;
          -  Compromised Immune System, including HIV positive serum status&#xD;
&#xD;
          -  Known life-threatening systemic disease&#xD;
&#xD;
          -  Patients with a history of seizures within the past year&#xD;
&#xD;
          -  Patients with current or a prior history of any psychiatric illness will be excluded.&#xD;
             Any presence or history of psychosis will be excluded. Patients with a significant&#xD;
             mood disorders including depression will be excluded. For the purpose of this study,&#xD;
             we consider a significant mood disorder to include any patient who has:&#xD;
&#xD;
               -  been under the care of a psychiatrist for over 3 months&#xD;
&#xD;
               -  taken antidepressant medications for greater than 6 months&#xD;
&#xD;
               -  has participated in cognitive-behavioral therapy&#xD;
&#xD;
               -  been hospitalized for the treatment of a psychiatric illness&#xD;
&#xD;
               -  received transcranial magnetic stimulation&#xD;
&#xD;
               -  received electroconvulsive therapy&#xD;
&#xD;
          -  Patients with risk factors for intraoperative or postoperative bleeding (platelet&#xD;
             count less than 100,000 per cubic millimeter, PT &gt; 14, PTT &gt; 36 or INR &gt; 1.3) or a&#xD;
             documented coagulopathy&#xD;
&#xD;
          -  Patients with brain tumors&#xD;
&#xD;
          -  Any illness that in the investigator's opinion preclude participation in this study.&#xD;
&#xD;
          -  Pregnancy or lactation.&#xD;
&#xD;
          -  Legal incapacity or limited legal capacity.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ernst - Martin, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University Children's Hospital, Zurich</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Ronald - Bauer, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Neurosurgey, Kantonsspital St. Gallen, Switzerland</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>MR-Center, University Children's Hospital</name>
      <address>
        <city>Zurich</city>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>October 2014</verification_date>
  <study_first_submitted>July 2, 2012</study_first_submitted>
  <study_first_submitted_qc>September 28, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2012</study_first_posted>
  <last_update_submitted>October 8, 2014</last_update_submitted>
  <last_update_submitted_qc>October 8, 2014</last_update_submitted_qc>
  <last_update_posted type="Estimate">October 9, 2014</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>FUS</keyword>
  <keyword>focused ultrasound</keyword>
  <keyword>functional brain disorder</keyword>
  <keyword>neuropathic pain</keyword>
  <keyword>movement disorders</keyword>
  <keyword>malignant brain tumors</keyword>
  <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>
  <!-- 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/NCT01698450
org study id: EK: 2012-0027
nct id: NCT01698450
lead sponsor: 
has dmc: Yes
The aim of this study is to asses the efficacy and the clinical safety of the transcranial
      magnetic resonance guided high intensity focused ultrasound system ExAblate 4000, InSightec
      Ltd. for functional neurosurgery in the treatment of movement disorders. The treatments to be
      conducted in this study are non-invasive, i.e. without opening the skull, and will create
      microthalamotomies in specific target areas such as thalamus, subthalamus and pallidum. The
      data obtained in this study will be used to evaluate the basic safety aspects of this new
      treatment technology and will serve as a basis for the clinical introduction of MR-guided
      ultrasound neurosurgery.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Basic Science
masking: None (Open Label)
measure: Lesion Size
time frame: 3 months
description: Size of lesion in the target area for each sonication as a function of applied energy/temperature.
measure: Patient Safety
time frame: 3 months
description: Number of Patients with Adverse Events as a Measure of Safety and Tolerability.
measure: Clinical efficacy and QOL
time frame: 3 months
description: Efficacy and QOL will be quantified on respective rating scales (specified in protocol).
arm group label: Focused Ultrasound for Movement Disorders
arm group type: Other
intervention type: Device
intervention name: Non-invasive intervention with focused ultrasound (ExAblate 4000)
description: Non-invasive brain intervention using MR-guided focused ultrasound
arm group label: Focused Ultrasound for Movement Disorders
other name: ExAblate 4000
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Ernst - Martin, MD
role: Principal Investigator
affiliation: University Children's Hospital, Zurich
last name: Ronald - Bauer, MD
role: Principal Investigator
affiliation: Neurosurgey, Kantonsspital St. Gallen, Switzerland
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Parkinson Disease
mesh term: Dystonia
mesh term: Movement Disorders
mesh term: Essential Tremor