<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/NCT03283150</url>
  </required_header>
  <id_info>
    <org_study_id>2016-1420</org_study_id>
    <secondary_id>A530900</secondary_id>
    <secondary_id>SMPH\ANESTHESIOLOGY\ANESTHESIO</secondary_id>
    <secondary_id>Protocol Version 2/17/2020</secondary_id>
    <nct_id>NCT03283150</nct_id>
  </id_info>
  <brief_title>Deep Brain Stimulation (DBS) Sedation</brief_title>
  <official_title>Effects of Anesthesia Drugs on Neuronal Activity in the Basal Ganglia and Thalamus During Deep Brain Stimulation Electrode Implantation Surgery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Wisconsin, Madison</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>Yes</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Deep brain stimulation (DBS) of different brain nuclei is a treatment for multiple brain&#xD;
      disorders. The subthalamic nucleus (STN) and globus pallidus have been used to treat advanced&#xD;
      Parkinson's disease for a long time. The ventral intermediate nucleus of the thalamus is an&#xD;
      effective target for treating essential tremor patients. STN and the internal segment of the&#xD;
      globus pallidus are useful targets for treating dystonia.&#xD;
&#xD;
      To achieve this optimal electrode localization, many centers perform electrophysiological&#xD;
      mapping of the target nuclei using microelectrode recording (MER). This way they can achieve&#xD;
      precise localization of the electrode. During the mapping procedure, microelectrodes are&#xD;
      passed through the target nuclei, and the electrical neuronal activity is observed and&#xD;
      recorded. The surgical team can identify the precise location of the target nuclei and its&#xD;
      borders according to the typical activity of its neurons.&#xD;
&#xD;
      This study will compare the activity of neurons in several DBS targets before, during and&#xD;
      after sedation with propofol, remifentanil and dexmedetomidine. The goal is to understand the&#xD;
      effects of anesthetics on the neuronal activity in these targets, allowing us to choose the&#xD;
      most appropriate sedation protocol to use during implantation of DBS electrodes in deep brain&#xD;
      structures (bearing in mind that each structure may have a different optimal protocol).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Deep brain stimulation (DBS) of different brain nuclei is evolving as an essential component&#xD;
      of the treatment for multiple brain disorders. The subthalamic nucleus (STN) and globus&#xD;
      pallidus have been used to treat advanced Parkinson's disease for a long time. The ventral&#xD;
      intermediate nucleus of the thalamus is an effective target for treating essential tremor&#xD;
      patients. STN and the internal segment of the globus pallidus are useful targets for treating&#xD;
      dystonia. Aside from movement disorders DBS has demonstrated efficacy in the treatment of&#xD;
      other conditions such as chronic pain, obsessive compulsive disorder, depression and&#xD;
      epilepsy. For these illnesses the specific brain region targeted depends upon the illness and&#xD;
      the patient's characteristics. As the indications for DBS increase in number, so grows the&#xD;
      number of patients that may be helped by this treatment. Increasing numbers of patients are&#xD;
      undergoing these procedures for various maladies at our center and at other locations&#xD;
      throughout the nation.&#xD;
&#xD;
      To achieve optimal clinical results and avoid side effects, the DBS electrode has to be&#xD;
      implanted precisely within the targeted region. This was demonstrated elegantly for&#xD;
      parkinsonian patients and the dorsolateral STN, but is likely to be the case for most DBS&#xD;
      indications. To achieve this optimal electrode localization, many centers perform&#xD;
      electrophysiological mapping of the target nuclei using microelectrode recording (MER). This&#xD;
      way they can achieve precise localization of the electrode. During the mapping procedure,&#xD;
      microelectrodes are passed through the target nuclei, and the electrical neuronal activity is&#xD;
      observed and recorded. The surgical team can identify the precise location of the target&#xD;
      nuclei and its borders according to the typical activity of its neurons.&#xD;
&#xD;
      Dexmedetomidine, propofol and remifentanyl are often used in awake neurosurgical procedures.&#xD;
      Dexmedetomidine provides sedation and amnesia with minimal respiratory depression, and&#xD;
      improves perioperative hemodynamic stability in neurosurgical patients. Propofol and&#xD;
      remifentanil have a much shorter duration of action, and thus allow rapid titration. Both&#xD;
      these agents allow reliable and safe sedation for awake craniotomies. However, the effects of&#xD;
      any of these three agents on the electrical activity, and whether they will allow safe&#xD;
      sedation during DBS electrode implantation at different targets and in different clinical&#xD;
      conditions is unclear.&#xD;
&#xD;
      This study will compare the activity of neurons in several DBS targets before, during and&#xD;
      after sedation with propofol, remifentanil and dexmedetomidine. The goal is to understand the&#xD;
      effects of anesthetics on the neuronal activity in these targets, allowing the study team to&#xD;
      choose the most appropriate sedation protocol to use during implantation of DBS electrodes in&#xD;
      deep brain structures (bearing in mind that each structure may have a different optimal&#xD;
      protocol).&#xD;
&#xD;
      The primary aim is to document the effects of commonly used anesthetic drugs on the neuronal&#xD;
      activity during MER in different brain structures that are used as targets for DBS&#xD;
      implantation.&#xD;
&#xD;
      The secondary aims is to Identifying effective sedation regimens for the different DBS&#xD;
      targets; (2) Documenting the time course of the different drug's effect on the neuronal&#xD;
      activity. Having this information will allow planning and performing sedation during the&#xD;
      procedure prior to the MER without affecting the quality of the MER. This may prove useful in&#xD;
      cases where no sedation regimen is completely devoid of effect on the MER; (3) Creating a&#xD;
      database that includes the neuronal activity changes at multiple brain regions under the&#xD;
      effect of different sedation drugs to enable further study of the effects of anesthetics on&#xD;
      brain regions and the mechanisms underlying loss of consciousness.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    Due to a decrease in scheduled study-eligible patients, we terminated the study prematurely&#xD;
  </why_stopped>
  <start_date type="Actual">December 1, 2017</start_date>
  <completion_date type="Actual">January 20, 2022</completion_date>
  <primary_completion_date type="Actual">January 20, 2022</primary_completion_date>
  <phase>Phase 4</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Sequential Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Sedatives Drugs Effects - Percent Change in Root Mean Square (RMS) of Electrical Activity</measure>
    <time_frame>45 minutes</time_frame>
    <description>Effects of propofol, remifentanil and dexmedetomidine on the neuronal activity during microelectrode recording (MER) in different brain structures that are used as target for DBS implantation will be measure.&#xD;
The RMS of the electrical activity as a measure of the spiking rate of neurons in the vicinity of the electrode tip. normalize the RMS to the baseline value recorded at the first 2-5 minutes of MER (before entering the target area) to compensate for differences between patients and recording electrodes. In order to calculate the change in the normalized RMS following sedation the investigators will compare the mean RMS during 2 minutes of the stable recording of the pre-sedation baseline to the mean RMS during stable sedation and following recovery.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mean Time in Minutes From Sedation to Recovery</measure>
    <time_frame>up to 57 minutes</time_frame>
    <description>This outocme meadsures the mean time from sedation to recovery.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Number of Individuals Examined for Neuronal Activity Changes at Multiple Brain Regions Under the Effect of Different Sedative Drugs</measure>
    <time_frame>1hrs 30 min</time_frame>
    <description>The number of subjects examining the neuronal activity changes at multiple brain regions under the effect of different sedation drugs to enable further study of the effects of anesthetics on brain regions and the mechanisms underlying loss of consciousness.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Brain</condition>
  <condition>Sedation</condition>
  <arm_group>
    <arm_group_label>Remifentanil</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Remifentanil will be administered to subjects during microelectrode recordings (MER).</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Propofol</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Propofol will be administered to subjects during MER.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Dexmedetomidine</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Dexmedetomidine will be administered to subjects during MER.</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Remifentanil</intervention_name>
    <description>Remifentanyl will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the bispectral index (BIS) values to normalize to awake level for the MER.</description>
    <arm_group_label>Remifentanil</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Propofol</intervention_name>
    <description>Propofol will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
    <arm_group_label>Propofol</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Dexmedetomidine</intervention_name>
    <description>Dexmedetomidine will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
    <arm_group_label>Dexmedetomidine</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  All patients scheduled to undergo DBS electrode implantation surgery with MER that&#xD;
             agree to participate in the experiment and sign an informed consent are candidates to&#xD;
             participate in the study, unless one of the exclusion criteria is met&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known or suspected obstructive sleep apnea.&#xD;
&#xD;
          2. Suspected difficult intubation.&#xD;
&#xD;
          3. Pregnancy (pregnancy test is standard care for women of childbearing age)&#xD;
&#xD;
          4. Under 18 years of age or over 85 years of age&#xD;
&#xD;
          5. Cognitive disability impairing understanding the experiment or signing the informed&#xD;
             consent form.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Corey A Amlong, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Wisconsin, Madison</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Wisconsin Hospital and Clinics</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53705</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Raz A, Eimerl D, Zaidel A, Bergman H, Israel Z. Propofol decreases neuronal population spiking activity in the subthalamic nucleus of Parkinsonian patients. Anesth Analg. 2010 Nov;111(5):1285-9. doi: 10.1213/ANE.0b013e3181f565f2. Epub 2010 Sep 14.</citation>
    <PMID>20841416</PMID>
  </reference>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>September 6, 2017</study_first_submitted>
  <study_first_submitted_qc>September 13, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 14, 2017</study_first_posted>
  <results_first_submitted>January 20, 2023</results_first_submitted>
  <results_first_submitted_qc>March 23, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">March 27, 2023</results_first_posted>
  <last_update_submitted>March 23, 2023</last_update_submitted>
  <last_update_submitted_qc>March 23, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 27, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Deep Brain Stimulation(DBS)</keyword>
  <keyword>Sedation</keyword>
  <keyword>DBS Implantation</keyword>
  <keyword>Microelectrode recording(MER)</keyword>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Dexmedetomidine</mesh_term>
    <mesh_term>Remifentanil</mesh_term>
    <mesh_term>Propofol</mesh_term>
  </intervention_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>February 17, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/50/NCT03283150/Prot_SAP_000.pdf</document_url>
    </provided_document>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>February 5, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/50/NCT03283150/ICF_001.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Remifentanil</title>
          <description>Remifentanil will be administered to subjects during microelectrode recordings (MER).&#xD;
Remifentanil: Remifentanyl will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the bispectral index (BIS) values to normalize to awake level for the MER.</description>
        </group>
        <group group_id="P2">
          <title>Propofol</title>
          <description>Propofol will be administered to subjects during MER.&#xD;
Propofol: Propofol will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
        </group>
        <group group_id="P3">
          <title>Dexmedetomidine</title>
          <description>Dexmedetomidine will be administered to subjects during MER.&#xD;
Dexmedetomidine: Dexmedetomidine will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</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 group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="14"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <population>No subjects were accrued to the baseline propofol and dexmedetomidine groups. The study was stopped early due to COVID decreasing participant flow and the frequency of the surgery dropping due to surgeon loss.</population>
      <group_list>
        <group group_id="B1">
          <title>Remifentanil</title>
          <description>Remifentanil will be administered to subjects during microelectrode recordings (MER).&#xD;
Remifentanil: Remifentanyl will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
        </group>
        <group group_id="B2">
          <title>Propofol</title>
          <description>Propofol will be administered to subjects during MER.&#xD;
Propofol: Propofol will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
        </group>
        <group group_id="B3">
          <title>Dexmedetomidine</title>
          <description>Dexmedetomidine will be administered to subjects during MER.&#xD;
Dexmedetomidine: Dexmedetomidine will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="20"/>
            <count group_id="B2" value="0"/>
            <count group_id="B3" value="0"/>
            <count group_id="B4" value="20"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="60" lower_limit="52" upper_limit="67"/>
                    <measurement group_id="B4" value="60" lower_limit="52" upper_limit="67"/>
                  </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="5"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B4" value="15"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B4" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B4" value="2"/>
                  </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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="18"/>
                    <measurement group_id="B4" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B4" value="2"/>
                  </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 group_id="B4" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Sedatives Drugs Effects - Percent Change in Root Mean Square (RMS) of Electrical Activity</title>
        <description>Effects of propofol, remifentanil and dexmedetomidine on the neuronal activity during microelectrode recording (MER) in different brain structures that are used as target for DBS implantation will be measure.&#xD;
The RMS of the electrical activity as a measure of the spiking rate of neurons in the vicinity of the electrode tip. normalize the RMS to the baseline value recorded at the first 2-5 minutes of MER (before entering the target area) to compensate for differences between patients and recording electrodes. In order to calculate the change in the normalized RMS following sedation the investigators will compare the mean RMS during 2 minutes of the stable recording of the pre-sedation baseline to the mean RMS during stable sedation and following recovery.</description>
        <time_frame>45 minutes</time_frame>
        <population>No subjects were accrued into the propofol or dexmedetomidine groups as COVID-19 struck and the number of procedures performed decreased substantially during and post-COVID.</population>
        <group_list>
          <group group_id="O1">
            <title>Remifentanil</title>
            <description>Remifentanil will be administered to subjects during microelectrode recordings (MER).&#xD;
Remifentanil: Remifentanyl will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
          </group>
          <group group_id="O2">
            <title>Propofol</title>
            <description>Propofol will be administered to subjects during MER.&#xD;
Propofol: Propofol will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
          </group>
          <group group_id="O3">
            <title>Dexmedetomidine</title>
            <description>Dexmedetomidine will be administered to subjects during MER.&#xD;
Dexmedetomidine: Dexmedetomidine will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
          </group>
        </group_list>
        <measure>
          <title>Sedatives Drugs Effects - Percent Change in Root Mean Square (RMS) of Electrical Activity</title>
          <description>Effects of propofol, remifentanil and dexmedetomidine on the neuronal activity during microelectrode recording (MER) in different brain structures that are used as target for DBS implantation will be measure.&#xD;
The RMS of the electrical activity as a measure of the spiking rate of neurons in the vicinity of the electrode tip. normalize the RMS to the baseline value recorded at the first 2-5 minutes of MER (before entering the target area) to compensate for differences between patients and recording electrodes. In order to calculate the change in the normalized RMS following sedation the investigators will compare the mean RMS during 2 minutes of the stable recording of the pre-sedation baseline to the mean RMS during stable sedation and following recovery.</description>
          <population>No subjects were accrued into the propofol or dexmedetomidine groups as COVID-19 struck and the number of procedures performed decreased substantially during and post-COVID.</population>
          <units>percent change</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.69" spread="0.37"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Mean Time in Minutes From Sedation to Recovery</title>
        <description>This outocme meadsures the mean time from sedation to recovery.</description>
        <time_frame>up to 57 minutes</time_frame>
        <population>No subjects were accrued to the propofol or dexmedetomidine groups.</population>
        <group_list>
          <group group_id="O1">
            <title>Remifentanil</title>
            <description>Remifentanil will be administered to subjects during microelectrode recordings (MER).&#xD;
Remifentanil: Remifentanyl will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
          </group>
          <group group_id="O2">
            <title>Propofol</title>
            <description>Propofol will be administered to subjects during MER.&#xD;
Propofol: Propofol will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
          </group>
          <group group_id="O3">
            <title>Dexmedetomidine</title>
            <description>Dexmedetomidine will be administered to subjects during MER.&#xD;
Dexmedetomidine: Dexmedetomidine will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
          </group>
        </group_list>
        <measure>
          <title>Mean Time in Minutes From Sedation to Recovery</title>
          <description>This outocme meadsures the mean time from sedation to recovery.</description>
          <population>No subjects were accrued to the propofol or dexmedetomidine groups.</population>
          <units>minutes</units>
          <param>Mean</param>
          <dispersion>Full Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="29.43" lower_limit="11" upper_limit="57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Number of Individuals Examined for Neuronal Activity Changes at Multiple Brain Regions Under the Effect of Different Sedative Drugs</title>
        <description>The number of subjects examining the neuronal activity changes at multiple brain regions under the effect of different sedation drugs to enable further study of the effects of anesthetics on brain regions and the mechanisms underlying loss of consciousness.</description>
        <time_frame>1hrs 30 min</time_frame>
        <population>No subjects were accrued to the propofol or dexmedetomidine groups due to COVID and the decrease in the frequency of the surgery being performed at the hospital.</population>
        <group_list>
          <group group_id="O1">
            <title>Remifentanil</title>
            <description>Remifentanil will be administered to subjects during microelectrode recordings (MER).&#xD;
Remifentanil: Remifentanyl will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
          </group>
          <group group_id="O2">
            <title>Propofol</title>
            <description>Propofol will be administered to subjects during MER.&#xD;
Propofol: Propofol will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
          </group>
          <group group_id="O3">
            <title>Dexmedetomidine</title>
            <description>Dexmedetomidine will be administered to subjects during MER.&#xD;
Dexmedetomidine: Dexmedetomidine will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
          </group>
        </group_list>
        <measure>
          <title>Number of Individuals Examined for Neuronal Activity Changes at Multiple Brain Regions Under the Effect of Different Sedative Drugs</title>
          <description>The number of subjects examining the neuronal activity changes at multiple brain regions under the effect of different sedation drugs to enable further study of the effects of anesthetics on brain regions and the mechanisms underlying loss of consciousness.</description>
          <population>No subjects were accrued to the propofol or dexmedetomidine groups due to COVID and the decrease in the frequency of the surgery being performed at the hospital.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="14"/>
                <count group_id="O2" value="0"/>
                <count group_id="O3" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="14"/>
                    <measurement group_id="O2" value="0"/>
                    <measurement group_id="O3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>during 1 study visit, up to 4 hours</time_frame>
      <desc>Participants were only recruited into the Remifentanil arm. Study was terminated early per COVID-19 pandemic.</desc>
      <group_list>
        <group group_id="E1">
          <title>Remifentanil</title>
          <description>Remifentanil will be administered to subjects during microelectrode recordings (MER).&#xD;
Remifentanil: Remifentanyl will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
        </group>
        <group group_id="E2">
          <title>Propofol</title>
          <description>Propofol will be administered to subjects during MER.&#xD;
Propofol: Propofol will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
        </group>
        <group group_id="E3">
          <title>Dexmedetomidine</title>
          <description>Dexmedetomidine will be administered to subjects during MER.&#xD;
Dexmedetomidine: Dexmedetomidine will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.</description>
        </group>
      </group_list>
      <serious_events>
        <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="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="0"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="0"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="14"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="0"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="0"/>
              </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>Jeremy Sullivan</name_or_title>
      <organization>University of Wisconsin-Madison</organization>
      <phone>6082639976</phone>
      <email>jasullivan@wisc.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/NCT03283150
org study id: 2016-1420
secondary id: A530900
secondary id: SMPH\ANESTHESIOLOGY\ANESTHESIO
secondary id: Protocol Version 2/17/2020
nct id: NCT03283150
lead sponsor: 
has dmc: Yes
is fda regulated drug: Yes
is fda regulated device: No
Deep brain stimulation (DBS) of different brain nuclei is a treatment for multiple brain
      disorders. The subthalamic nucleus (STN) and globus pallidus have been used to treat advanced
      Parkinson's disease for a long time. The ventral intermediate nucleus of the thalamus is an
      effective target for treating essential tremor patients. STN and the internal segment of the
      globus pallidus are useful targets for treating dystonia.

      To achieve this optimal electrode localization, many centers perform electrophysiological
      mapping of the target nuclei using microelectrode recording (MER). This way they can achieve
      precise localization of the electrode. During the mapping procedure, microelectrodes are
      passed through the target nuclei, and the electrical neuronal activity is observed and
      recorded. The surgical team can identify the precise location of the target nuclei and its
      borders according to the typical activity of its neurons.

      This study will compare the activity of neurons in several DBS targets before, during and
      after sedation with propofol, remifentanil and dexmedetomidine. The goal is to understand the
      effects of anesthetics on the neuronal activity in these targets, allowing us to choose the
      most appropriate sedation protocol to use during implantation of DBS electrodes in deep brain
      structures (bearing in mind that each structure may have a different optimal protocol).
Deep brain stimulation (DBS) of different brain nuclei is evolving as an essential component
      of the treatment for multiple brain disorders. The subthalamic nucleus (STN) and globus
      pallidus have been used to treat advanced Parkinson's disease for a long time. The ventral
      intermediate nucleus of the thalamus is an effective target for treating essential tremor
      patients. STN and the internal segment of the globus pallidus are useful targets for treating
      dystonia. Aside from movement disorders DBS has demonstrated efficacy in the treatment of
      other conditions such as chronic pain, obsessive compulsive disorder, depression and
      epilepsy. For these illnesses the specific brain region targeted depends upon the illness and
      the patient's characteristics. As the indications for DBS increase in number, so grows the
      number of patients that may be helped by this treatment. Increasing numbers of patients are
      undergoing these procedures for various maladies at our center and at other locations
      throughout the nation.

      To achieve optimal clinical results and avoid side effects, the DBS electrode has to be
      implanted precisely within the targeted region. This was demonstrated elegantly for
      parkinsonian patients and the dorsolateral STN, but is likely to be the case for most DBS
      indications. To achieve this optimal electrode localization, many centers perform
      electrophysiological mapping of the target nuclei using microelectrode recording (MER). This
      way they can achieve precise localization of the electrode. During the mapping procedure,
      microelectrodes are passed through the target nuclei, and the electrical neuronal activity is
      observed and recorded. The surgical team can identify the precise location of the target
      nuclei and its borders according to the typical activity of its neurons.

      Dexmedetomidine, propofol and remifentanyl are often used in awake neurosurgical procedures.
      Dexmedetomidine provides sedation and amnesia with minimal respiratory depression, and
      improves perioperative hemodynamic stability in neurosurgical patients. Propofol and
      remifentanil have a much shorter duration of action, and thus allow rapid titration. Both
      these agents allow reliable and safe sedation for awake craniotomies. However, the effects of
      any of these three agents on the electrical activity, and whether they will allow safe
      sedation during DBS electrode implantation at different targets and in different clinical
      conditions is unclear.

      This study will compare the activity of neurons in several DBS targets before, during and
      after sedation with propofol, remifentanil and dexmedetomidine. The goal is to understand the
      effects of anesthetics on the neuronal activity in these targets, allowing the study team to
      choose the most appropriate sedation protocol to use during implantation of DBS electrodes in
      deep brain structures (bearing in mind that each structure may have a different optimal
      protocol).

      The primary aim is to document the effects of commonly used anesthetic drugs on the neuronal
      activity during MER in different brain structures that are used as targets for DBS
      implantation.

      The secondary aims is to Identifying effective sedation regimens for the different DBS
      targets; (2) Documenting the time course of the different drug's effect on the neuronal
      activity. Having this information will allow planning and performing sedation during the
      procedure prior to the MER without affecting the quality of the MER. This may prove useful in
      cases where no sedation regimen is completely devoid of effect on the MER; (3) Creating a
      database that includes the neuronal activity changes at multiple brain regions under the
      effect of different sedation drugs to enable further study of the effects of anesthetics on
      brain regions and the mechanisms underlying loss of consciousness.
allocation: Non-Randomized
intervention model: Sequential Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Sedatives Drugs Effects - Percent Change in Root Mean Square (RMS) of Electrical Activity
time frame: 45 minutes
description: Effects of propofol, remifentanil and dexmedetomidine on the neuronal activity during microelectrode recording (MER) in different brain structures that are used as target for DBS implantation will be measure.
The RMS of the electrical activity as a measure of the spiking rate of neurons in the vicinity of the electrode tip. normalize the RMS to the baseline value recorded at the first 2-5 minutes of MER (before entering the target area) to compensate for differences between patients and recording electrodes. In order to calculate the change in the normalized RMS following sedation the investigators will compare the mean RMS during 2 minutes of the stable recording of the pre-sedation baseline to the mean RMS during stable sedation and following recovery.
measure: Mean Time in Minutes From Sedation to Recovery
time frame: up to 57 minutes
description: This outocme meadsures the mean time from sedation to recovery.
measure: Number of Individuals Examined for Neuronal Activity Changes at Multiple Brain Regions Under the Effect of Different Sedative Drugs
time frame: 1hrs 30 min
description: The number of subjects examining the neuronal activity changes at multiple brain regions under the effect of different sedation drugs to enable further study of the effects of anesthetics on brain regions and the mechanisms underlying loss of consciousness.
arm group label: Remifentanil
arm group type: Active Comparator
description: Remifentanil will be administered to subjects during microelectrode recordings (MER).
arm group label: Propofol
arm group type: Active Comparator
description: Propofol will be administered to subjects during MER.
arm group label: Dexmedetomidine
arm group type: Active Comparator
description: Dexmedetomidine will be administered to subjects during MER.
intervention type: Drug
intervention name: Remifentanil
description: Remifentanyl will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the bispectral index (BIS) values to normalize to awake level for the MER.
arm group label: Remifentanil
intervention type: Drug
intervention name: Propofol
description: Propofol will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.
arm group label: Propofol
intervention type: Drug
intervention name: Dexmedetomidine
description: Dexmedetomidine will be administered for 10 -15 minutes before initiating the MER phase and the patient will be allow to wake up and the BIS values to normalize to awake level for the MER.
arm group label: Dexmedetomidine
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: No
last name: Corey A Amlong, MD
role: Principal Investigator
affiliation: University of Wisconsin, Madison
facility: 
country: United States
citation: Raz A, Eimerl D, Zaidel A, Bergman H, Israel Z. Propofol decreases neuronal population spiking activity in the subthalamic nucleus of Parkinsonian patients. Anesth Analg. 2010 Nov;111(5):1285-9. doi: 10.1213/ANE.0b013e3181f565f2. Epub 2010 Sep 14.
PMID: 20841416
responsible party type: Sponsor
mesh term: Dexmedetomidine
mesh term: Remifentanil
mesh term: Propofol
provided document: 
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 