<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/NCT02246374</url>
  </required_header>
  <id_info>
    <org_study_id>PD003</org_study_id>
    <nct_id>NCT02246374</nct_id>
  </id_info>
  <brief_title>ExAblate Transcranial MRgFUS of the Subthalamic Nucleus for Treatment of Parkinson's Disease</brief_title>
  <official_title>A Randomized Feasibility Clinical Trial of the Management of the Medically-Refractory Motor Symptoms of Advanced Idiopathic Parkinson's Disease With Unilateral Lesioning of the Subthalamic Nucleus Using the ExAblate Transcranial System</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>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is primarily a safety protocol to evaluate the safety of subthalamotomy using&#xD;
      Transcranial ExAblate for treatment of Parkinson's Disease (PD) motor features.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study is designed as a prospective, randomized, double-blind (to subjects and&#xD;
      examiners), two-arm (ExAblate treated arm vs ExAblate Sham treated control arm) feasibility&#xD;
      study. All treated subjects will be followed for 12 months.&#xD;
&#xD;
      Data will be collected to establish the basic safety and clinical efficacy of this type of&#xD;
      treatment as the basis for later studies that will evaluate the full clinical efficacy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Active, not recruiting</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Anticipated">December 2023</completion_date>
  <primary_completion_date type="Anticipated">June 2023</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>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Incidence and severity of adverse events</measure>
    <time_frame>Baseline to 4 months post treatment</time_frame>
    <description>Safety will evaluate the incidence and severity of adverse events associated with ExAblate subthalamotomy for the treatment of Parkinson's Disease motor features.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Mean change in MDS-UPDRS Part III scores</measure>
    <time_frame>Baseline to 4 months post treatment</time_frame>
    <description>This is a feasibility trial with no hypothesis testing. Primary efficacy will be evaluated using basic summary statistics including comparison of between- and within-group differences in the mean change (from baseline to 4 months) of the motor MDS-UPDRS Part III score for the side contralateral to subthalamotomy in the off-medication condition.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Long Term Adverse Events Profile</measure>
    <time_frame>Baseline to 12- months post treatment</time_frame>
    <description>Additional safety will be evaluated by follow up of adverse events through 12 months post treatment.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Mean change in MDS-UPDRS total score</measure>
    <time_frame>Baseline to 12- months post treatment</time_frame>
    <description>Duration of outcomes will be further evaluated using the MDS-UPDRS total score</description>
  </other_outcome>
  <other_outcome>
    <measure>Mean change in MDS-UPDRS Part IV scores</measure>
    <time_frame>Baseline to 12-months post treatment</time_frame>
    <description>Long term impact of ExAblate transcranial pallidotomy will be further evaluated using the MPS-UPDRS Part IV scores</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">7</enrollment>
  <condition>Parkinson's Disease</condition>
  <arm_group>
    <arm_group_label>ExAblate Treated Arm</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>ExAblate Transcranial System subthalamotomy for motor symptoms of Parkinson's Disease.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>ExAblate Sham Treated Arm</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>ExAblate Transcranial System sham subthalamotomy for motor symptoms of Parkinson's Disease. Sham subjects completing the 4 Month visit may be offered the actual ExAblate subthalamotomy.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>ExAblate Transcranial System</intervention_name>
    <description>ExAblate Transcranial System subthalamotomy for symptoms of Parkinson's Disease</description>
    <arm_group_label>ExAblate Sham Treated Arm</arm_group_label>
    <arm_group_label>ExAblate Treated Arm</arm_group_label>
    <other_name>MRgFUS</other_name>
    <other_name>FUS</other_name>
    <other_name>Focused Ultrasound</other_name>
    <other_name>MR Guided Focused Ultrasound</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Men and women, age 30 years and older&#xD;
&#xD;
          2. Subjects who are able and willing to give informed consent and able to attend all&#xD;
             study visits&#xD;
&#xD;
          3. Subjects with a diagnosis of idiopathic PD by UK Brain Bank Criteria as confirmed by a&#xD;
             movement disorder neurologist at the site&#xD;
&#xD;
          4. Levodopa responsive as defined by at least a 30% reduction in MDS-UPDRS motor&#xD;
             sub-scale in the ON vs OFF medication state&#xD;
&#xD;
          5. Disabling motor clinical features not optimally controlled by an adequate medication&#xD;
             prescription. An adequate medication prescription is defined as a therapeutic dose of&#xD;
             each medication or the development of side effects as the medication dose is titrated&#xD;
&#xD;
          6. Predominant disability from one side of the body (i.e unilateral or markedly&#xD;
             asymmetric disease) as determined by movement disorders neurologist and neurosurgeon&#xD;
&#xD;
          7. Subjects should be on a stable dose of all PD medications for 30 days prior to study&#xD;
             entry&#xD;
&#xD;
          8. Subthalamic nucleus is visible on MRI so that it can be targeted by the ExAblate&#xD;
             device&#xD;
&#xD;
          9. Subjects should have a Screening motor assessment of ≥ 35 while OFF medications on the&#xD;
             MDS-UPDRS&#xD;
&#xD;
         10. Subject is able to communicate sensations during the ExAblate Transcranial procedure&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Hoehn and Yahr stage in the ON medication state of 2.5 or greater&#xD;
&#xD;
          2. Presence of severe dyskinesia as noted by a score of 3 or 4 on questions 4.1 and 4.2&#xD;
             of the MDS-UPDRS&#xD;
&#xD;
          3. Presence of other central neurodegenerative disease suspected on neurological&#xD;
             examination. These include: multisystem atrophy, progressive supranuclear palsy,&#xD;
             corticobasal syndrome, dementia with Lewy bodies, and Alzheimer's disease&#xD;
&#xD;
          4. Any suspicion that Parkinsonian symptoms are a side effect from neuroleptic&#xD;
             medications&#xD;
&#xD;
          5. Subjects who have had deep brain stimulation or a prior stereotactic ablation of the&#xD;
             basal ganglia&#xD;
&#xD;
          6. Presence of significant cognitive impairment defined as score ≤ 21 on the Montreal&#xD;
             Cognitive Assessment (MoCA) or Mattis Dementia Rating Scale of 120 or lower&#xD;
&#xD;
          7. Unstable psychiatric disease, defined as active uncontrolled depressive symptoms,&#xD;
             psychosis, delusions, hallucinations, or suicidal ideation. Subjects with stable,&#xD;
             chronic anxiety or depressive disorders may be included provided their medications&#xD;
             have been stable for at least 60 days prior to study entry and if deemed appropriately&#xD;
             managed by the site neuropsychologist&#xD;
&#xD;
          8. Subjects with significant depression as determined following a comprehensive&#xD;
             assessment by a neuropsychologist. Significant depression is being defined&#xD;
             quantitatively as a score of greater than 14 on the Beck Depression Inventory&#xD;
&#xD;
          9. Legal incapacity or limited legal capacity as determined by the neuropsychologist&#xD;
&#xD;
         10. Subjects 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 the preceding 12 month period:&#xD;
&#xD;
               1. 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;
               2. 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;
               3. Recurrent substance-related legal problems (such as arrests for substance related&#xD;
                  disorderly conduct)&#xD;
&#xD;
               4. 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;
         11. Subjects with unstable cardiac status including:&#xD;
&#xD;
               1. Unstable angina pectoris on medication&#xD;
&#xD;
               2. Subjects with documented myocardial infarction within six months of protocol&#xD;
                  entry&#xD;
&#xD;
               3. Significant congestive heart failure defined with ejection fraction &lt; 40&#xD;
&#xD;
               4. Subjects with unstable ventricular arrhythmias&#xD;
&#xD;
               5. Subjects with atrial arrhythmias that are not rate-controlled&#xD;
&#xD;
         12. Severe hypertension (diastolic BP &gt; 100 on medication)&#xD;
&#xD;
         13. History of or current medical condition resulting in abnormal bleeding and/or&#xD;
             coagulopathy&#xD;
&#xD;
         14. 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;
         15. Subjects with risk factors for intraoperative or postoperative bleeding as indicated&#xD;
             by: platelet count less than 100,000 per cubic millimeter, a documented clinical&#xD;
             coagulopathy, or INR coagulation studies exceeding the institution's laboratory&#xD;
             standard&#xD;
&#xD;
         16. Patient with severely impaired renal function with estimated glomerular filtration&#xD;
             rate &lt;30 mL/min/1.73m2 (or per local standards should that be more restrictive) and/or&#xD;
             who is on dialysis&#xD;
&#xD;
         17. Subjects with standard contraindications for MR imaging such as non-MRI compatible&#xD;
             implanted metallic devices including cardiac pacemakers, size limitations, etc.&#xD;
&#xD;
         18. Significant claustrophobia that cannot be managed with mild medication&#xD;
&#xD;
         19. Subjects who weigh more than the upper weight limit of the MR table and who cannot fit&#xD;
             into the MR scanner&#xD;
&#xD;
         20. Subjects who are not able or willing to tolerate the required prolonged stationary&#xD;
             supine position during treatment&#xD;
&#xD;
         21. History of intracranial hemorrhage&#xD;
&#xD;
         22. History of multiple strokes, or a stroke within past 6 months&#xD;
&#xD;
         23. Subjects with a history of seizures within the past year&#xD;
&#xD;
         24. Subjects with brain tumors&#xD;
&#xD;
         25. Subjects with intracranial aneurysms requiring treatment or arterial venous&#xD;
             malformations (AVMs) requiring treatment&#xD;
&#xD;
         26. Are participating or have participated in another clinical trial in the last 30 days&#xD;
&#xD;
         27. Any illness that in the investigator's opinion preclude participation in this study&#xD;
&#xD;
         28. Subjects unable to communicate with the investigator and staff&#xD;
&#xD;
         29. Pregnancy or lactation&#xD;
&#xD;
         30. Subjects who have an overall Skull Density Ration lower than 0.40 as calculated from&#xD;
             the screening CT&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jeff Elias, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Virginia</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Virginia</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22908</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2022</verification_date>
  <study_first_submitted>September 18, 2014</study_first_submitted>
  <study_first_submitted_qc>September 18, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 22, 2014</study_first_posted>
  <last_update_submitted>December 19, 2022</last_update_submitted>
  <last_update_submitted_qc>December 19, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 20, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Parkinson's Disease</keyword>
  <keyword>ExAblate</keyword>
  <keyword>MRgFUS</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</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/NCT02246374
org study id: PD003
nct id: NCT02246374
lead sponsor: 
has dmc: Yes
This is primarily a safety protocol to evaluate the safety of subthalamotomy using
      Transcranial ExAblate for treatment of Parkinson's Disease (PD) motor features.
This study is designed as a prospective, randomized, double-blind (to subjects and
      examiners), two-arm (ExAblate treated arm vs ExAblate Sham treated control arm) feasibility
      study. All treated subjects will be followed for 12 months.

      Data will be collected to establish the basic safety and clinical efficacy of this type of
      treatment as the basis for later studies that will evaluate the full clinical efficacy.
allocation: Randomized
intervention model: Crossover Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Incidence and severity of adverse events
time frame: Baseline to 4 months post treatment
description: Safety will evaluate the incidence and severity of adverse events associated with ExAblate subthalamotomy for the treatment of Parkinson's Disease motor features.
measure: Mean change in MDS-UPDRS Part III scores
time frame: Baseline to 4 months post treatment
description: This is a feasibility trial with no hypothesis testing. Primary efficacy will be evaluated using basic summary statistics including comparison of between- and within-group differences in the mean change (from baseline to 4 months) of the motor MDS-UPDRS Part III score for the side contralateral to subthalamotomy in the off-medication condition.
measure: Long Term Adverse Events Profile
time frame: Baseline to 12- months post treatment
description: Additional safety will be evaluated by follow up of adverse events through 12 months post treatment.
measure: Mean change in MDS-UPDRS total score
time frame: Baseline to 12- months post treatment
description: Duration of outcomes will be further evaluated using the MDS-UPDRS total score
measure: Mean change in MDS-UPDRS Part IV scores
time frame: Baseline to 12-months post treatment
description: Long term impact of ExAblate transcranial pallidotomy will be further evaluated using the MPS-UPDRS Part IV scores
arm group label: ExAblate Treated Arm
arm group type: Experimental
description: ExAblate Transcranial System subthalamotomy for motor symptoms of Parkinson's Disease.
arm group label: ExAblate Sham Treated Arm
arm group type: Sham Comparator
description: ExAblate Transcranial System sham subthalamotomy for motor symptoms of Parkinson's Disease. Sham subjects completing the 4 Month visit may be offered the actual ExAblate subthalamotomy.
intervention type: Device
intervention name: ExAblate Transcranial System
description: ExAblate Transcranial System subthalamotomy for symptoms of Parkinson's Disease
arm group label: ExAblate Sham Treated Arm
arm group label: ExAblate Treated Arm
other name: MRgFUS
other name: FUS
other name: Focused Ultrasound
other name: MR Guided Focused Ultrasound
criteria: 
gender: All
minimum age: 30 Years
maximum age: N/A
healthy volunteers: No
last name: Jeff Elias, MD
role: Principal Investigator
affiliation: University of Virginia
facility: 
country: United States
responsible party type: Sponsor
mesh term: Parkinson Disease