<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/NCT03270657</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00085076</org_study_id>
    <secondary_id>UH3NS103468</secondary_id>
    <nct_id>NCT03270657</nct_id>
  </id_info>
  <brief_title>Scalar Closed Loop Intraoperative Study</brief_title>
  <official_title>Scalar Closed-Loop STN/GPi DBS Based on Evoked and Spontaneous Potentials (Intraoperative Studies)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Dennis Turner, M.D.</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institute of Neurological Disorders and Stroke (NINDS)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>Duke University</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to measure neural activity during deep brain stimulation (DBS).&#xD;
      There are two types of neural activity that we will record from DBS electrodes during this&#xD;
      study: DBS local evoked potentials (DLEPs) and spontaneous, local field potentials (LFPs). We&#xD;
      will measure the effects of varying stimulation parameters on both the neural activity and&#xD;
      changes in motor symptoms -- bradykinesia and tremor -- in subjects with Parkinson's disease&#xD;
      (PD). Correlating neural activity characteristics with changes in symptoms will improve our&#xD;
      understanding of the mechanisms of action of DBS. This intraoperative study will specifically&#xD;
      compare our ability to record neural activity using circuitry developed at Duke for this&#xD;
      purpose [Kent et al, 2015] to a new, implanted pulse generator (IPG; RC+S) developed by&#xD;
      Medtronic. These intraoperative studies will specifically test a preliminary version of the&#xD;
      RC+S (that is not designed for implantation), and will lead to a clinical trial assessing the&#xD;
      efficacy of the implantable RC+S IPG in PD patients once this device is available and&#xD;
      approved for this trial.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The investigator will measure DBS local evoked potentials (DLEPs) and/or local field&#xD;
      potentials (LFPs) together with motor symptoms (tremor and/or bradykinesia) in response to&#xD;
      deep brain stimulation (DBS). The study will be conducted in the operating room at Duke&#xD;
      University Medical Center. Additional operating room costs will be covered by institutional&#xD;
      resources at Duke. The study will be performed on subjects who are undergoing implantation of&#xD;
      the DBS system during an awake, stereotactic procedure for PD.&#xD;
&#xD;
      The subject group will only include patients undergoing a DBS implant procedure for PD. The&#xD;
      surgical procedure will proceed as needed for treatment of Parkinson's disease (PD),&#xD;
      including implantation of the DBS electrode (one into STN or dual electrodes into STN and&#xD;
      GPi/GPe) into the targeted regions of the brain. For this research, subjects will receive&#xD;
      temporary (~45 min) percutaneous extensions to the DBS electrode(s) and DBS lead cannula&#xD;
      after implantation. These temporary extensions will connect to both our Duke stimulation and&#xD;
      recording system or the Medtronic RC+S test recording system, alternating as needed, to allow&#xD;
      recording and direct comparison of neural DLEP responses and/or LFPs using the two different&#xD;
      stimulation/recording systems. Details of the stimulation and recording system are provided&#xD;
      in the Study Interventions section. After the study is completed, the second DBS electrode&#xD;
      (if placed) and the temporary percutaneous extensions will be removed. Then, the ordinary&#xD;
      clinical conduct of the procedure will continue for treatment of the patient's movement&#xD;
      disorder.&#xD;
&#xD;
      The investigator will measure tremor and/or bradykinesia in persons with PD during DBS.&#xD;
      Subjects will be familiarized with and able to practice the evaluation tasks before&#xD;
      preparation for surgery. Further, they will be asked to discontinue use of dopaminergic&#xD;
      and/or anti-tremor medications overnight prior to the study (as is the clinical routine), to&#xD;
      reduce variability of motor symptoms due to the time course of medications. The investigator&#xD;
      will conduct evaluations using unilateral stimulation, with the limb contralateral to the&#xD;
      side of stimulation used for measurement of motor symptoms. Subjects may also be asked to&#xD;
      rate any side effects that they experience on a 0 - 10 scale.&#xD;
&#xD;
      Contacts on the subject's DBS electrode will be used for stimulation and recording. The four&#xD;
      DBS contacts are designated as 0-1-2-3 in the ventral-dorsal direction. For monopolar&#xD;
      stimulation, a single contact will be used for cathodic stimulation (1- or 2-) and a&#xD;
      conductive pad will be placed on the subject's skin, outside of the sterile field, to serve&#xD;
      as the return electrode. The recording contacts will be two other contacts on the DBS lead.&#xD;
      For bipolar stimulation, DBS pulses will be applied between two electrode contacts, and the&#xD;
      recording contacts will be the two remaining free contacts. The stimulus waveform will be a&#xD;
      charge-balanced biphasic pulse, with charge restricted to values below the limit set by the&#xD;
      manufacturer, 30 µC/cm2. Another conductive pad will be placed on the subject to serve as the&#xD;
      recording reference. For subjects undergoing the DBS implantation surgery, the DBS lead&#xD;
      cannula or a surgical retractor normally placed at the cranial incision site may also be used&#xD;
      as the recording reference or return electrode.&#xD;
&#xD;
      In subjects with tremor-dominant PD, the investigator will record both the tremor and DLEP&#xD;
      and/or LFP responses from the DBS electrode. Several trials will be conducted with different&#xD;
      stimulation amplitudes, frequencies (≤185 Hz), temporal patterns, and contact configurations.&#xD;
      The stimulation amplitude will be less than that identified to be uncomfortable to the&#xD;
      subject or that generates side effects, as determined by a neurologist and/or neurosurgeon&#xD;
      during the initial testing phase following implantation. The different stimulation parameters&#xD;
      will be delivered in randomized order, and the subject will be blinded to the parameters.&#xD;
      Measurements will be made during 2-minute trials, in which stimulation will be off for the&#xD;
      first minute of the trial, and on for the remaining minute. At 30 s into both the off&#xD;
      (baseline) and on phases of the trial, tremor will be measured for 20 s. The neural activity&#xD;
      will also be measured from the electrode during both the off and on phases. The total amount&#xD;
      of time necessary for data collection will be about 45 minutes.&#xD;
&#xD;
      Tremor will be measured using an accelerometer taped to the back of the subject's hand, and&#xD;
      with the wrist extended such that the hand is parallel to the forearm. The elbow may either&#xD;
      be supported or unsupported, depending on which induces greater tremor (determined prior to&#xD;
      any trials in each subject). Tremor as measured by an accelerometer correlates well with&#xD;
      clinical tremor rating scales [Elble et al, 2006].&#xD;
&#xD;
      In subjects with Parkinson's disease who do not have dominant tremor symptoms, the&#xD;
      investigator will record both bradykinesia testing responses and DLEP and/or LFP potentials.&#xD;
      Several trials will be conducted with different stimulation amplitudes, mean frequencies&#xD;
      (≤185 Hz), temporal patterns, and contact configurations. The maximum amplitude delivered&#xD;
      will be determined as described as above. The different stimulation parameters will be&#xD;
      delivered in randomized order, and the subject will be blinded to the parameters.&#xD;
      Measurements will be made in 10-minute trials, in which stimulation will be off for the first&#xD;
      five minutes of the trial, and on for the remaining five minutes. At approximately 90, 210&#xD;
      and 250 s into both the off (baseline) and on phases of the trial, bradykinesia will be&#xD;
      measured for 20 s. The neural activity will also be measured from the electrode during both&#xD;
      the off and on phases of the trial. The total amount of time necessary for data collection&#xD;
      will be about 45 minutes.&#xD;
&#xD;
      For bradykinesia measurements, the subject will be instructed to press alternately the right&#xD;
      and left buttons of a computer mouse with the index and middle finger of their hand as&#xD;
      rapidly and regularly as possible. Bradykinesia will be measured as the timing of alternating&#xD;
      finger presses, a validated test of bradykinesia [Taylor-Tavares et al., 2005].&#xD;
&#xD;
      Before DBS surgery, the subject's baseline pathological motor symptoms may be assessed in the&#xD;
      pre-operative setting, to familiarize the patient with the task ahead of the implant&#xD;
      procedure. Tremor or bradykinesia will be measured using the previously-described&#xD;
      accelerometer measurement or the mouse click task, respectively. This task will take about 5&#xD;
      minutes, and will be performed in the DBS-off condition. No sedation will be administered&#xD;
      until after this has been completed.&#xD;
&#xD;
      Following DBS surgery, the subject's pre-operative MRI and post-operative high-resolution CT&#xD;
      scans may be used to determine the location of DBS electrode contacts within the brain.&#xD;
      Placement of the electrode during DBS implant surgery will not be altered by the research&#xD;
      study.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">April 5, 2018</start_date>
  <completion_date type="Actual">March 26, 2019</completion_date>
  <primary_completion_date type="Actual">March 26, 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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of Participants With Recorded Evoked Neural Signals From Deep Brain Stimulation (DBS) Electrodes During DBS for Parkinson's Disease.</measure>
    <time_frame>End of procedure, approximately 45 minutes</time_frame>
    <description>Measured by the ability to record neural activity through DBS electrodes using circuitry developed at Duke for this purpose and/or a new implantable pulse generator (IPG; RC+S) developed by Medtronic. These intraoperative studies will specifically test a preliminary version of the RC+S that is not designed for implantation.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Recorded DBS Local Evoked Potentials (DLEPs).</measure>
    <time_frame>End of procedure, approximately 45 minutes</time_frame>
    <description>Measured by the ability to record DLEPs (changes in local electric field in response to DBS stimulation) through DBS electrodes using circuitry developed at Duke for this purpose and/or a new implantable pulse generator (IPG; RC+S) developed by Medtronic. These intraoperative studies will specifically test a preliminary version of the RC+S that is not designed for implantation. The DLEP recordings will be serially averaged with stimulus-triggering to remove random noise while preserving the evoked response.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Participants With Recorded Spontaneous, Local Field Potentials (LFPs).</measure>
    <time_frame>End of procedure, approximately 45 minutes</time_frame>
    <description>Measured by the ability to record LFPs (electrical activity in the local region of the DBS electrode) through DBS electrodes using circuitry developed at Duke for this purpose and/or a new implantable pulse generator (IPG; RC+S) developed by Medtronic. These intraoperative studies will specifically test a preliminary version of the RC+S that is not designed for implantation.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">5</enrollment>
  <condition>Parkinson Disease</condition>
  <arm_group>
    <arm_group_label>Intraoperative Recording During DBS Implant Surgery</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Participants will be recruited and enrolled from individuals who have Parkinson's disease (PD) and who already are scheduled to undergo the planned deep brain electrode placement for treatment of their movement disorder. Intraoperative recordings of participants' neural signals will be made through the implanted deep brain electrode(s).</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>IPG; RC+S</intervention_name>
    <description>We will measure the effects of varying stimulation parameters on the neural activity in subjects with Parkinson's disease (PD).</description>
    <arm_group_label>Intraoperative Recording During DBS Implant Surgery</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Parkinson's disease (PD) patients who are scheduled to already undergo the planned&#xD;
             deep brain electrode placement for treatment of their movement disorder at Duke&#xD;
             University Medical Center.&#xD;
&#xD;
          -  Able to understand the study and consent form, and interested in proceeding with&#xD;
             research during the invasive brain surgery to receive a DBS system for treatment of&#xD;
             PD.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability to execute the motor tasks during the study.&#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>Dennis Turner, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Duke University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Duke University Medical Center</name>
      <address>
        <city>Durham</city>
        <state>North Carolina</state>
        <zip>27710</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2020</verification_date>
  <study_first_submitted>August 31, 2017</study_first_submitted>
  <study_first_submitted_qc>August 31, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 1, 2017</study_first_posted>
  <results_first_submitted>March 6, 2020</results_first_submitted>
  <results_first_submitted_qc>March 6, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">March 23, 2020</results_first_posted>
  <last_update_submitted>March 6, 2020</last_update_submitted>
  <last_update_submitted_qc>March 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">March 23, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>Duke University</investigator_affiliation>
    <investigator_full_name>Dennis Turner, M.D.</investigator_full_name>
    <investigator_title>Professor of Neurosurgery, Neurosurgery</investigator_title>
  </responsible_party>
  <keyword>Deep Brain Stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>March 8, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/57/NCT03270657/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Intraoperative Recording During DBS Implant Surgery</title>
          <description>Participants will be recruited and enrolled from individuals who have Parkinson's disease (PD) and who already are scheduled to undergo the planned deep brain electrode placement for treatment of their movement disorder. Intraoperative recordings of participants' neural signals will be made through the implanted deep brain electrode(s).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="5"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="4"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Intraoperative Recording During DBS Implant Surgery</title>
          <description>Participants will be recruited and enrolled from individuals who have Parkinson's disease (PD) and who already are scheduled to undergo the planned deep brain electrode placement for treatment of their movement disorder. Intraoperative recordings of participants' neural signals will be made through the implanted deep brain electrode(s).</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="5"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </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="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Number of Participants With Recorded Evoked Neural Signals From Deep Brain Stimulation (DBS) Electrodes During DBS for Parkinson's Disease.</title>
        <description>Measured by the ability to record neural activity through DBS electrodes using circuitry developed at Duke for this purpose and/or a new implantable pulse generator (IPG; RC+S) developed by Medtronic. These intraoperative studies will specifically test a preliminary version of the RC+S that is not designed for implantation.</description>
        <time_frame>End of procedure, approximately 45 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intraoperative Recording During DBS Implant Surgery</title>
            <description>Participants will be recruited and enrolled from individuals who have Parkinson's disease (PD) and who already are scheduled to undergo the planned deep brain electrode placement for treatment of their movement disorder. Intraoperative recordings of participants' neural signals will be made through the implanted deep brain electrode(s).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Recorded Evoked Neural Signals From Deep Brain Stimulation (DBS) Electrodes During DBS for Parkinson's Disease.</title>
          <description>Measured by the ability to record neural activity through DBS electrodes using circuitry developed at Duke for this purpose and/or a new implantable pulse generator (IPG; RC+S) developed by Medtronic. These intraoperative studies will specifically test a preliminary version of the RC+S that is not designed for implantation.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Recorded DBS Local Evoked Potentials (DLEPs).</title>
        <description>Measured by the ability to record DLEPs (changes in local electric field in response to DBS stimulation) through DBS electrodes using circuitry developed at Duke for this purpose and/or a new implantable pulse generator (IPG; RC+S) developed by Medtronic. These intraoperative studies will specifically test a preliminary version of the RC+S that is not designed for implantation. The DLEP recordings will be serially averaged with stimulus-triggering to remove random noise while preserving the evoked response.</description>
        <time_frame>End of procedure, approximately 45 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intraoperative Recording During DBS Implant Surgery</title>
            <description>Participants will be recruited and enrolled from individuals who have Parkinson's disease (PD) and who already are scheduled to undergo the planned deep brain electrode placement for treatment of their movement disorder. Intraoperative recordings of participants' neural signals will be made through the implanted deep brain electrode(s).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Recorded DBS Local Evoked Potentials (DLEPs).</title>
          <description>Measured by the ability to record DLEPs (changes in local electric field in response to DBS stimulation) through DBS electrodes using circuitry developed at Duke for this purpose and/or a new implantable pulse generator (IPG; RC+S) developed by Medtronic. These intraoperative studies will specifically test a preliminary version of the RC+S that is not designed for implantation. The DLEP recordings will be serially averaged with stimulus-triggering to remove random noise while preserving the evoked response.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Participants With Recorded Spontaneous, Local Field Potentials (LFPs).</title>
        <description>Measured by the ability to record LFPs (electrical activity in the local region of the DBS electrode) through DBS electrodes using circuitry developed at Duke for this purpose and/or a new implantable pulse generator (IPG; RC+S) developed by Medtronic. These intraoperative studies will specifically test a preliminary version of the RC+S that is not designed for implantation.</description>
        <time_frame>End of procedure, approximately 45 minutes</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Intraoperative Recording During DBS Implant Surgery</title>
            <description>Participants will be recruited and enrolled from individuals who have Parkinson's disease (PD) and who already are scheduled to undergo the planned deep brain electrode placement for treatment of their movement disorder. Intraoperative recordings of participants' neural signals will be made through the implanted deep brain electrode(s).</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Participants With Recorded Spontaneous, Local Field Potentials (LFPs).</title>
          <description>Measured by the ability to record LFPs (electrical activity in the local region of the DBS electrode) through DBS electrodes using circuitry developed at Duke for this purpose and/or a new implantable pulse generator (IPG; RC+S) developed by Medtronic. These intraoperative studies will specifically test a preliminary version of the RC+S that is not designed for implantation.</description>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="5"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>30 days</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Intraoperative Recording During DBS Implant Surgery</title>
          <description>Participants will be recruited and enrolled from individuals who have Parkinson's disease (PD) and who already are scheduled to undergo the planned deep brain electrode placement for treatment of their movement disorder. Intraoperative recordings of participants' neural signals will be made through the implanted deep brain electrode(s).</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-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="5"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>infection</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>somnolence</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-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="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>hyperhidrosis</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="5"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE 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>
    <point_of_contact>
      <name_or_title>Dr. Dennis Turner</name_or_title>
      <organization>Duke University</organization>
      <phone>919-684-7777</phone>
      <email>dennis.turner@duke.edu</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/NCT03270657
org study id: Pro00085076
secondary id: UH3NS103468
nct id: NCT03270657
lead sponsor: 
collaborator: 
collaborator: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
is us export: No
The purpose of this study is to measure neural activity during deep brain stimulation (DBS).
      There are two types of neural activity that we will record from DBS electrodes during this
      study: DBS local evoked potentials (DLEPs) and spontaneous, local field potentials (LFPs). We
      will measure the effects of varying stimulation parameters on both the neural activity and
      changes in motor symptoms -- bradykinesia and tremor -- in subjects with Parkinson's disease
      (PD). Correlating neural activity characteristics with changes in symptoms will improve our
      understanding of the mechanisms of action of DBS. This intraoperative study will specifically
      compare our ability to record neural activity using circuitry developed at Duke for this
      purpose [Kent et al, 2015] to a new, implanted pulse generator (IPG; RC+S) developed by
      Medtronic. These intraoperative studies will specifically test a preliminary version of the
      RC+S (that is not designed for implantation), and will lead to a clinical trial assessing the
      efficacy of the implantable RC+S IPG in PD patients once this device is available and
      approved for this trial.
The investigator will measure DBS local evoked potentials (DLEPs) and/or local field
      potentials (LFPs) together with motor symptoms (tremor and/or bradykinesia) in response to
      deep brain stimulation (DBS). The study will be conducted in the operating room at Duke
      University Medical Center. Additional operating room costs will be covered by institutional
      resources at Duke. The study will be performed on subjects who are undergoing implantation of
      the DBS system during an awake, stereotactic procedure for PD.

      The subject group will only include patients undergoing a DBS implant procedure for PD. The
      surgical procedure will proceed as needed for treatment of Parkinson's disease (PD),
      including implantation of the DBS electrode (one into STN or dual electrodes into STN and
      GPi/GPe) into the targeted regions of the brain. For this research, subjects will receive
      temporary (~45 min) percutaneous extensions to the DBS electrode(s) and DBS lead cannula
      after implantation. These temporary extensions will connect to both our Duke stimulation and
      recording system or the Medtronic RC+S test recording system, alternating as needed, to allow
      recording and direct comparison of neural DLEP responses and/or LFPs using the two different
      stimulation/recording systems. Details of the stimulation and recording system are provided
      in the Study Interventions section. After the study is completed, the second DBS electrode
      (if placed) and the temporary percutaneous extensions will be removed. Then, the ordinary
      clinical conduct of the procedure will continue for treatment of the patient's movement
      disorder.

      The investigator will measure tremor and/or bradykinesia in persons with PD during DBS.
      Subjects will be familiarized with and able to practice the evaluation tasks before
      preparation for surgery. Further, they will be asked to discontinue use of dopaminergic
      and/or anti-tremor medications overnight prior to the study (as is the clinical routine), to
      reduce variability of motor symptoms due to the time course of medications. The investigator
      will conduct evaluations using unilateral stimulation, with the limb contralateral to the
      side of stimulation used for measurement of motor symptoms. Subjects may also be asked to
      rate any side effects that they experience on a 0 - 10 scale.

      Contacts on the subject's DBS electrode will be used for stimulation and recording. The four
      DBS contacts are designated as 0-1-2-3 in the ventral-dorsal direction. For monopolar
      stimulation, a single contact will be used for cathodic stimulation (1- or 2-) and a
      conductive pad will be placed on the subject's skin, outside of the sterile field, to serve
      as the return electrode. The recording contacts will be two other contacts on the DBS lead.
      For bipolar stimulation, DBS pulses will be applied between two electrode contacts, and the
      recording contacts will be the two remaining free contacts. The stimulus waveform will be a
      charge-balanced biphasic pulse, with charge restricted to values below the limit set by the
      manufacturer, 30 µC/cm2. Another conductive pad will be placed on the subject to serve as the
      recording reference. For subjects undergoing the DBS implantation surgery, the DBS lead
      cannula or a surgical retractor normally placed at the cranial incision site may also be used
      as the recording reference or return electrode.

      In subjects with tremor-dominant PD, the investigator will record both the tremor and DLEP
      and/or LFP responses from the DBS electrode. Several trials will be conducted with different
      stimulation amplitudes, frequencies (≤185 Hz), temporal patterns, and contact configurations.
      The stimulation amplitude will be less than that identified to be uncomfortable to the
      subject or that generates side effects, as determined by a neurologist and/or neurosurgeon
      during the initial testing phase following implantation. The different stimulation parameters
      will be delivered in randomized order, and the subject will be blinded to the parameters.
      Measurements will be made during 2-minute trials, in which stimulation will be off for the
      first minute of the trial, and on for the remaining minute. At 30 s into both the off
      (baseline) and on phases of the trial, tremor will be measured for 20 s. The neural activity
      will also be measured from the electrode during both the off and on phases. The total amount
      of time necessary for data collection will be about 45 minutes.

      Tremor will be measured using an accelerometer taped to the back of the subject's hand, and
      with the wrist extended such that the hand is parallel to the forearm. The elbow may either
      be supported or unsupported, depending on which induces greater tremor (determined prior to
      any trials in each subject). Tremor as measured by an accelerometer correlates well with
      clinical tremor rating scales [Elble et al, 2006].

      In subjects with Parkinson's disease who do not have dominant tremor symptoms, the
      investigator will record both bradykinesia testing responses and DLEP and/or LFP potentials.
      Several trials will be conducted with different stimulation amplitudes, mean frequencies
      (≤185 Hz), temporal patterns, and contact configurations. The maximum amplitude delivered
      will be determined as described as above. The different stimulation parameters will be
      delivered in randomized order, and the subject will be blinded to the parameters.
      Measurements will be made in 10-minute trials, in which stimulation will be off for the first
      five minutes of the trial, and on for the remaining five minutes. At approximately 90, 210
      and 250 s into both the off (baseline) and on phases of the trial, bradykinesia will be
      measured for 20 s. The neural activity will also be measured from the electrode during both
      the off and on phases of the trial. The total amount of time necessary for data collection
      will be about 45 minutes.

      For bradykinesia measurements, the subject will be instructed to press alternately the right
      and left buttons of a computer mouse with the index and middle finger of their hand as
      rapidly and regularly as possible. Bradykinesia will be measured as the timing of alternating
      finger presses, a validated test of bradykinesia [Taylor-Tavares et al., 2005].

      Before DBS surgery, the subject's baseline pathological motor symptoms may be assessed in the
      pre-operative setting, to familiarize the patient with the task ahead of the implant
      procedure. Tremor or bradykinesia will be measured using the previously-described
      accelerometer measurement or the mouse click task, respectively. This task will take about 5
      minutes, and will be performed in the DBS-off condition. No sedation will be administered
      until after this has been completed.

      Following DBS surgery, the subject's pre-operative MRI and post-operative high-resolution CT
      scans may be used to determine the location of DBS electrode contacts within the brain.
      Placement of the electrode during DBS implant surgery will not be altered by the research
      study.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Other
masking: None (Open Label)
measure: Number of Participants With Recorded Evoked Neural Signals From Deep Brain Stimulation (DBS) Electrodes During DBS for Parkinson's Disease.
time frame: End of procedure, approximately 45 minutes
description: Measured by the ability to record neural activity through DBS electrodes using circuitry developed at Duke for this purpose and/or a new implantable pulse generator (IPG; RC+S) developed by Medtronic. These intraoperative studies will specifically test a preliminary version of the RC+S that is not designed for implantation.
measure: Number of Participants With Recorded DBS Local Evoked Potentials (DLEPs).
time frame: End of procedure, approximately 45 minutes
description: Measured by the ability to record DLEPs (changes in local electric field in response to DBS stimulation) through DBS electrodes using circuitry developed at Duke for this purpose and/or a new implantable pulse generator (IPG; RC+S) developed by Medtronic. These intraoperative studies will specifically test a preliminary version of the RC+S that is not designed for implantation. The DLEP recordings will be serially averaged with stimulus-triggering to remove random noise while preserving the evoked response.
measure: Number of Participants With Recorded Spontaneous, Local Field Potentials (LFPs).
time frame: End of procedure, approximately 45 minutes
description: Measured by the ability to record LFPs (electrical activity in the local region of the DBS electrode) through DBS electrodes using circuitry developed at Duke for this purpose and/or a new implantable pulse generator (IPG; RC+S) developed by Medtronic. These intraoperative studies will specifically test a preliminary version of the RC+S that is not designed for implantation.
arm group label: Intraoperative Recording During DBS Implant Surgery
arm group type: Other
description: Participants will be recruited and enrolled from individuals who have Parkinson's disease (PD) and who already are scheduled to undergo the planned deep brain electrode placement for treatment of their movement disorder. Intraoperative recordings of participants' neural signals will be made through the implanted deep brain electrode(s).
intervention type: Device
intervention name: IPG; RC+S
description: We will measure the effects of varying stimulation parameters on the neural activity in subjects with Parkinson's disease (PD).
arm group label: Intraoperative Recording During DBS Implant Surgery
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Dennis Turner, M.D.
role: Principal Investigator
affiliation: Duke University
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: Duke University
investigator full name: Dennis Turner, M.D.
investigator title: Professor of Neurosurgery, Neurosurgery
mesh term: Parkinson Disease
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 