<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/NCT02263885</url>
  </required_header>
  <id_info>
    <org_study_id>PD002</org_study_id>
    <nct_id>NCT02263885</nct_id>
  </id_info>
  <brief_title>ExAblate Transcranial MRgFUS of the Globus Pallidum for Treatment of Parkinson's Disease</brief_title>
  <official_title>A Feasibility Clinical Trial of the Management of the Medically-Refractory Dyskinesia Symptoms of Advanced Idiopathic Parkinson's Disease With Unilateral Lesioning of the Globus Pallidum 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>
      The proposed study will evaluate the safety, and initial efficacy of using the ExAblate&#xD;
      Transcranial to create a unilateral lesion in the globus pallidus as an adjunct to PD&#xD;
      medications in subjects who are over 30 years of age and considered medication-refractory&#xD;
      with advanced idiopathic Parkinson's disease (PD).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The purpose of this study is to evaluate the safety and initial clinical effectiveness of&#xD;
      ExAblate Transcranial unilateral thermal ablation of the globus pallidus of subjects&#xD;
      suffering from medication-refractory, advanced idiopathic PD.&#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>Completed</overall_status>
  <start_date>April 2015</start_date>
  <completion_date type="Actual">July 26, 2019</completion_date>
  <primary_completion_date type="Actual">May 15, 2019</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>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>Month 24</time_frame>
    <description>The primary outcome of this feasibility trial was safety. Adverse Events were categorized by physicians as mild, moderate, or severe. Events resulting in impairment, requiring intervention to preclude impairment, or that were life threatening, and deaths were reported by physicians as Serious Adverse Events. Outcomes are entered in the adverse events module.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Unified Dyskinesia Rating Scale Total Score.</measure>
    <time_frame>Screening, Month 3, Month 6, Month 12, Month 24</time_frame>
    <description>The Unified Dyskinesia Rating Scale Total score assesses overall involuntary movements associated with the treatment of Parkinson's disease. The minimum score possible is 0. The maximum total score possible is 104. High scores show worse symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Unified Dyskinesia Rating Scale (UDysRS), Part III</measure>
    <time_frame>Screening, Month 3, Month 6, Month 12, Month 24</time_frame>
    <description>The Unified Dyskinesia Ratient Scale (UDysRS) was developed to assess involuntary movements often associated with the treatment of Parkinson's disease. Part III evaluates the intensity of impairment of dyskinesia with respect to the performance of 7 tasks on a scale of 0 to 4. The sum of the Part III score ranges 0 to 28 and high scores show worse symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III Motor Exam</measure>
    <time_frame>Screening, Month 3, Month 6, Month 12, Month 24</time_frame>
    <description>The Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS UPDRSP Part III motor exam focuses specifically on the treated side tremor and motor fluctuations. Each of 11 items are scored from 0 to 4 for a total score minimum of 0 and a maximum of 44 points. High scores show worse symptoms.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mood Disorders Society - Unified Parkinson's Disease Rating Scale Part II</measure>
    <time_frame>Screening, Month 3, Month 6, Month 12, Month 24</time_frame>
    <description>.Part II of the Mood Disorders Society Unified Parkinson's Disease Rating Scale focuses on the impact of symptoms on motor aspects of daily living. Part II consists of 13 items scored from 0 to 4 for a maximum score of 52. High Part II scores indicate worse (greater) impact.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mood Disorder Society Unified Parkinson's Disease Rating Scale Part IV</measure>
    <time_frame>Screening, Month 3, Month 6, Month 12, Month 24</time_frame>
    <description>Part IV of the Mood Disorder Society Unified Parkinson's Disease Rating Scale assesses dyskinesias that include OFF-state dystonia; items include time spent with dyskinesia, functional impact of dyskinesia, time spent in the OFF state, functional impact of fluctuations, complexity of motor fluctuations and painful OFF state dystonia. Six items are scored 0 to 4 with a maximum total score of 24. High scores indicate worse symptoms.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Parkinson's Disease</condition>
  <arm_group>
    <arm_group_label>ExAblate Transcranial System</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Transcranial ExAblate MRgFUS</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>ExAblate Transcranial System</intervention_name>
    <description>Transcranial MRgFUS</description>
    <arm_group_label>ExAblate Transcranial System</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;
          -  Men and women, age 30 years and older&#xD;
&#xD;
          -  Subjects who are able and willing to give informed consent and able to attend all&#xD;
             study visits through 24 Months&#xD;
&#xD;
          -  Subjects with a diagnosis of idiopathic PD&#xD;
&#xD;
          -  Levodopa responsive as defined by at least a 30% reduction in MDS-UPDRS motor subscale&#xD;
             in the ON vs OFF medication state.&#xD;
&#xD;
          -  Disabling motor complications of PD on optimum medical treatment&#xD;
&#xD;
          -  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;
          -  Subjects should be on a stable dose of all PD medications for 30 days prior to study&#xD;
             entry.&#xD;
&#xD;
          -  Subject is able to communicate sensations during the ExAblate Transcranial procedure.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  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;
          -  Any suspicion that Parkinsonian symptoms are a side effect from neuroleptic&#xD;
             medications.&#xD;
&#xD;
          -  Subjects who have had deep brain stimulation or a prior stereotactic ablation of the&#xD;
             basal ganglia&#xD;
&#xD;
          -  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;
          -  Subjects with significant depression as determined following a comprehensive&#xD;
             assessment by a neuropsychologist.&#xD;
&#xD;
          -  Legal incapacity or limited legal capacity as determined by the neuropsychologist&#xD;
&#xD;
          -  Subjects exhibiting any behavior(s) consistent with ethanol or substance abuse&#xD;
&#xD;
          -  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;
          -  Severe hypertension (diastolic BP &gt; 100 on medication)&#xD;
&#xD;
          -  Current medical condition resulting in 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;
          -  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;
          -  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;
          -  Subjects with standard contraindications for MR imaging such as non-MRI compatible&#xD;
             implanted metallic devices including cardiac pacemakers, size limitations, etc.&#xD;
&#xD;
          -  Significant claustrophobia that cannot be managed with mild medication.&#xD;
&#xD;
          -  Subjects who are not able or willing to tolerate the required prolonged stationary&#xD;
             supine position during treatment.&#xD;
&#xD;
          -  History of intracranial hemorrhage&#xD;
&#xD;
          -  History of multiple strokes, or a stroke within past 6 months&#xD;
&#xD;
          -  Subjects with a history of seizures within the past year&#xD;
&#xD;
          -  Subjects with brain tumors&#xD;
&#xD;
          -  Subjects with intracranial aneurysms requiring treatment or arterial venous&#xD;
             malformations (AVMs) requiring treatment.&#xD;
&#xD;
          -  Are participating or have participated in another clinical trial in the last 30 days&#xD;
&#xD;
          -  Any illness that in the investigator's opinion preclude participation in this study.&#xD;
&#xD;
          -  Subjects unable to communicate with the investigator and staff.&#xD;
&#xD;
          -  Pregnancy or lactation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Stanford University Medical Center</name>
      <address>
        <city>Stanford</city>
        <state>California</state>
        <zip>94305</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Maryland Medical System</name>
      <address>
        <city>Baltimore</city>
        <state>Maryland</state>
        <zip>21201</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Brigham and Women's Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02115</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>The Ohio State Wexner Medical Center</name>
      <address>
        <city>Columbus</city>
        <state>Ohio</state>
        <zip>43210</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <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 2021</verification_date>
  <study_first_submitted>October 8, 2014</study_first_submitted>
  <study_first_submitted_qc>October 8, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 13, 2014</study_first_posted>
  <results_first_submitted>September 7, 2021</results_first_submitted>
  <results_first_submitted_qc>December 20, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 19, 2022</results_first_posted>
  <last_update_submitted>December 20, 2021</last_update_submitted>
  <last_update_submitted_qc>December 20, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 19, 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>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>August 31, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/85/NCT02263885/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>ExAblate Transcranial System Test Arm</title>
          <description>Transcranial ExAblate MRgFUS&#xD;
Transcranial MRgFUS lesioning of the Globus Pallidum</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="20"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="10"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
              </participants_list>
            </drop_withdraw_reason>
            <drop_withdraw_reason>
              <title>Alternative Treatment</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>ExAblate Transcranial System Test Arm</title>
          <description>Transcranial ExAblate MRgFUS&#xD;
Transcranial MRgFUS lesioning of the Globus Pallidum</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="56.4" spread="11.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Race</title>
              <category_list>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Hispanic</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Other</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Adverse Events</title>
        <description>The primary outcome of this feasibility trial was safety. Adverse Events were categorized by physicians as mild, moderate, or severe. Events resulting in impairment, requiring intervention to preclude impairment, or that were life threatening, and deaths were reported by physicians as Serious Adverse Events. Outcomes are entered in the adverse events module.</description>
        <time_frame>Month 24</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ExAblate Transcranial System Test Arm</title>
            <description>Transcranial ExAblate MRgFUS&#xD;
Transcranial MRgFUS lesioning of the Globus Pallidum</description>
          </group>
        </group_list>
        <measure>
          <title>Adverse Events</title>
          <description>The primary outcome of this feasibility trial was safety. Adverse Events were categorized by physicians as mild, moderate, or severe. Events resulting in impairment, requiring intervention to preclude impairment, or that were life threatening, and deaths were reported by physicians as Serious Adverse Events. Outcomes are entered in the adverse events module.</description>
          <units>Number of Adverse Events</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Unified Dyskinesia Rating Scale Total Score.</title>
        <description>The Unified Dyskinesia Rating Scale Total score assesses overall involuntary movements associated with the treatment of Parkinson's disease. The minimum score possible is 0. The maximum total score possible is 104. High scores show worse symptoms.</description>
        <time_frame>Screening, Month 3, Month 6, Month 12, Month 24</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ExAblate Transcranial System</title>
            <description>Transcranial ExAblate MRgFUS&#xD;
ExAblate Transcranial System: Transcranial MRgFUS</description>
          </group>
        </group_list>
        <measure>
          <title>Unified Dyskinesia Rating Scale Total Score.</title>
          <description>The Unified Dyskinesia Rating Scale Total score assesses overall involuntary movements associated with the treatment of Parkinson's disease. The minimum score possible is 0. The maximum total score possible is 104. High scores show worse symptoms.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Screening</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="36.1" lower_limit="31.2" upper_limit="40.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.9" lower_limit="9.3" upper_limit="20.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="16.9" lower_limit="10.1" upper_limit="23.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.5" lower_limit="11.9" upper_limit="27.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="23.1" lower_limit="12.4" upper_limit="33.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Unified Dyskinesia Rating Scale (UDysRS), Part III</title>
        <description>The Unified Dyskinesia Ratient Scale (UDysRS) was developed to assess involuntary movements often associated with the treatment of Parkinson's disease. Part III evaluates the intensity of impairment of dyskinesia with respect to the performance of 7 tasks on a scale of 0 to 4. The sum of the Part III score ranges 0 to 28 and high scores show worse symptoms.</description>
        <time_frame>Screening, Month 3, Month 6, Month 12, Month 24</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ExAblate Transcranial System Test Arm</title>
            <description>Transcranial ExAblate MRgFUS&#xD;
Transcranial MRgFUS lesioning of the Globus Pallidum</description>
          </group>
        </group_list>
        <measure>
          <title>Unified Dyskinesia Rating Scale (UDysRS), Part III</title>
          <description>The Unified Dyskinesia Ratient Scale (UDysRS) was developed to assess involuntary movements often associated with the treatment of Parkinson's disease. Part III evaluates the intensity of impairment of dyskinesia with respect to the performance of 7 tasks on a scale of 0 to 4. The sum of the Part III score ranges 0 to 28 and high scores show worse symptoms.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Screening</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.2" lower_limit="7.5" upper_limit="12.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" lower_limit="2.4" upper_limit="6.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0" lower_limit="2.7" upper_limit="9.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.1" lower_limit="1.7" upper_limit="6.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.8" lower_limit="2.3" upper_limit="9.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III Motor Exam</title>
        <description>The Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS UPDRSP Part III motor exam focuses specifically on the treated side tremor and motor fluctuations. Each of 11 items are scored from 0 to 4 for a total score minimum of 0 and a maximum of 44 points. High scores show worse symptoms.</description>
        <time_frame>Screening, Month 3, Month 6, Month 12, Month 24</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ExAblate Transcranial System Test Arm</title>
            <description>Transcranial ExAblate MRgFUS&#xD;
Transcranial MRgFUS lesioning of the Globus Pallidum</description>
          </group>
        </group_list>
        <measure>
          <title>Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III Motor Exam</title>
          <description>The Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS UPDRSP Part III motor exam focuses specifically on the treated side tremor and motor fluctuations. Each of 11 items are scored from 0 to 4 for a total score minimum of 0 and a maximum of 44 points. High scores show worse symptoms.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Screening</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.0" lower_limit="17.5" upper_limit="22.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.6" lower_limit="8.7" upper_limit="12.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.1" lower_limit="9.6" upper_limit="12.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.5" lower_limit="8.2" upper_limit="12.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.3" lower_limit="9.8" upper_limit="14.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mood Disorders Society - Unified Parkinson's Disease Rating Scale Part II</title>
        <description>.Part II of the Mood Disorders Society Unified Parkinson's Disease Rating Scale focuses on the impact of symptoms on motor aspects of daily living. Part II consists of 13 items scored from 0 to 4 for a maximum score of 52. High Part II scores indicate worse (greater) impact.</description>
        <time_frame>Screening, Month 3, Month 6, Month 12, Month 24</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ExAblate Transcranial System Test Arm</title>
            <description>Transcranial ExAblate MRgFUS&#xD;
Transcranial MRgFUS lesioning of the Globus Pallidum</description>
          </group>
        </group_list>
        <measure>
          <title>Mood Disorders Society - Unified Parkinson's Disease Rating Scale Part II</title>
          <description>.Part II of the Mood Disorders Society Unified Parkinson's Disease Rating Scale focuses on the impact of symptoms on motor aspects of daily living. Part II consists of 13 items scored from 0 to 4 for a maximum score of 52. High Part II scores indicate worse (greater) impact.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Screening</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14.0" lower_limit="10.7" upper_limit="17.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7.4" lower_limit="5.14" upper_limit="9.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.7" lower_limit="5.1" upper_limit="10.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.4" lower_limit="8.6" upper_limit="14.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.8" lower_limit="9.4" upper_limit="18.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mood Disorder Society Unified Parkinson's Disease Rating Scale Part IV</title>
        <description>Part IV of the Mood Disorder Society Unified Parkinson's Disease Rating Scale assesses dyskinesias that include OFF-state dystonia; items include time spent with dyskinesia, functional impact of dyskinesia, time spent in the OFF state, functional impact of fluctuations, complexity of motor fluctuations and painful OFF state dystonia. Six items are scored 0 to 4 with a maximum total score of 24. High scores indicate worse symptoms.</description>
        <time_frame>Screening, Month 3, Month 6, Month 12, Month 24</time_frame>
        <group_list>
          <group group_id="O1">
            <title>ExAblate Transcranial System Test Arm</title>
            <description>Transcranial ExAblate MRgFUS&#xD;
Transcranial MRgFUS lesioning of the Globus Pallidum</description>
          </group>
        </group_list>
        <measure>
          <title>Mood Disorder Society Unified Parkinson's Disease Rating Scale Part IV</title>
          <description>Part IV of the Mood Disorder Society Unified Parkinson's Disease Rating Scale assesses dyskinesias that include OFF-state dystonia; items include time spent with dyskinesia, functional impact of dyskinesia, time spent in the OFF state, functional impact of fluctuations, complexity of motor fluctuations and painful OFF state dystonia. Six items are scored 0 to 4 with a maximum total score of 24. High scores indicate worse symptoms.</description>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="20"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Screening</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.1" lower_limit="8.6" upper_limit="13.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 3</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.4" lower_limit="4.5" upper_limit="8.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6.0" lower_limit="4.4" upper_limit="7.6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.9" lower_limit="4.0" upper_limit="7.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 24</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="8.7" lower_limit="5.8" upper_limit="11.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Adverse event data was collected for 24 months.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>ExAblate Transcranial System Test Arm</title>
          <description>Transcranial ExAblate MRgFUS&#xD;
Transcranial MRgFUS lesioning of the Globus Pallidum</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Stroke</sub_title>
                <description>A subject experienced a stroke 2 years post-treatment. The DSMB adjudicated the stroke as unrelated to the device or procedure.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_assessment>Systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="15" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Gastrointestinal disorders</title>
            <event_list>
              <event>
                <sub_title>Nausea/Vomiting</sub_title>
                <description>Tranient nausea/vomiting, resolving within 72 hours of treatment</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Drooling</sub_title>
                <description>Drooling related to Parkinson's Disease</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <description>Transient headache, resolving within 72 hours of treatment</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Sonication Related Head Pain</sub_title>
                <description>Transient sonication related head pain, resolving within 72 hours of treatment.</description>
                <counts group_id="E1" events="7" subjects_affected="7" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Headache</sub_title>
                <description>Procedure related headache</description>
                <counts group_id="E1" events="5" subjects_affected="5" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Dyskinesia</sub_title>
                <description>Dyskinesia related to Parkinson's Disease</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Fine Motor Problems</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Dysarthria</sub_title>
                <description>Pallidotomy related dysarthria</description>
                <counts group_id="E1" events="4" subjects_affected="4" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Anxiety</sub_title>
                <description>Procedure related anxiety</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Skin and subcutaneous tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Bruise</sub_title>
                <description>Bruise unrelated to device or procedure</description>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="20"/>
              </event>
              <event>
                <sub_title>Facial Edema</sub_title>
                <description>Edema related to stereotactic frame</description>
                <counts group_id="E1" events="3" subjects_affected="3" subjects_at_risk="20"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>This is a single-arm, open label, feasibility trial. Analyses included basic descriptive statistics. No hypothesis testing was proposed.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Nadir Alikacem, PhD</name_or_title>
      <organization>InSightec</organization>
      <phone>214-630-2000</phone>
      <email>nadira@insightec.com</email>
    </point_of_contact>
  </clinical_results>
</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/NCT02263885
org study id: PD002
nct id: NCT02263885
lead sponsor: 
has dmc: Yes
The proposed study will evaluate the safety, and initial efficacy of using the ExAblate
      Transcranial to create a unilateral lesion in the globus pallidus as an adjunct to PD
      medications in subjects who are over 30 years of age and considered medication-refractory
      with advanced idiopathic Parkinson's disease (PD).
The purpose of this study is to evaluate the safety and initial clinical effectiveness of
      ExAblate Transcranial unilateral thermal ablation of the globus pallidus of subjects
      suffering from medication-refractory, advanced idiopathic PD.

      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: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Events
time frame: Month 24
description: The primary outcome of this feasibility trial was safety. Adverse Events were categorized by physicians as mild, moderate, or severe. Events resulting in impairment, requiring intervention to preclude impairment, or that were life threatening, and deaths were reported by physicians as Serious Adverse Events. Outcomes are entered in the adverse events module.
measure: Unified Dyskinesia Rating Scale Total Score.
time frame: Screening, Month 3, Month 6, Month 12, Month 24
description: The Unified Dyskinesia Rating Scale Total score assesses overall involuntary movements associated with the treatment of Parkinson's disease. The minimum score possible is 0. The maximum total score possible is 104. High scores show worse symptoms.
measure: Unified Dyskinesia Rating Scale (UDysRS), Part III
time frame: Screening, Month 3, Month 6, Month 12, Month 24
description: The Unified Dyskinesia Ratient Scale (UDysRS) was developed to assess involuntary movements often associated with the treatment of Parkinson's disease. Part III evaluates the intensity of impairment of dyskinesia with respect to the performance of 7 tasks on a scale of 0 to 4. The sum of the Part III score ranges 0 to 28 and high scores show worse symptoms.
measure: Movement Disorders Society - Unified Parkinson's Disease Rating Scale (MDS-UPDRS), Part III Motor Exam
time frame: Screening, Month 3, Month 6, Month 12, Month 24
description: The Movement Disorder Society - Unified Parkinson's Disease Rating Scale (MDS UPDRSP Part III motor exam focuses specifically on the treated side tremor and motor fluctuations. Each of 11 items are scored from 0 to 4 for a total score minimum of 0 and a maximum of 44 points. High scores show worse symptoms.
measure: Mood Disorders Society - Unified Parkinson's Disease Rating Scale Part II
time frame: Screening, Month 3, Month 6, Month 12, Month 24
description: .Part II of the Mood Disorders Society Unified Parkinson's Disease Rating Scale focuses on the impact of symptoms on motor aspects of daily living. Part II consists of 13 items scored from 0 to 4 for a maximum score of 52. High Part II scores indicate worse (greater) impact.
measure: Mood Disorder Society Unified Parkinson's Disease Rating Scale Part IV
time frame: Screening, Month 3, Month 6, Month 12, Month 24
description: Part IV of the Mood Disorder Society Unified Parkinson's Disease Rating Scale assesses dyskinesias that include OFF-state dystonia; items include time spent with dyskinesia, functional impact of dyskinesia, time spent in the OFF state, functional impact of fluctuations, complexity of motor fluctuations and painful OFF state dystonia. Six items are scored 0 to 4 with a maximum total score of 24. High scores indicate worse symptoms.
arm group label: ExAblate Transcranial System
arm group type: Experimental
description: Transcranial ExAblate MRgFUS
intervention type: Device
intervention name: ExAblate Transcranial System
description: Transcranial MRgFUS
arm group label: ExAblate Transcranial System
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
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Parkinson Disease
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: This is a single-arm, open label, feasibility trial. Analyses included basic descriptive statistics. No hypothesis testing was proposed.
point of contact: 