xml: <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/NCT06016686</url>
    </required_header>
    <id_info>
      <org_study_id>VNS</org_study_id>
      <nct_id>NCT06016686</nct_id>
    </id_info>
    <brief_title>Microelectrode Recordings From the Vagus Nerve in Awake Humans</brief_title>
    <official_title>Microelectrode Recordings From the Vagus Nerve in Awake Humans</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>University of Minnesota</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
    </sponsors>
    <source>University of Minnesota</source>
    <oversight_info>
      <has_dmc>No</has_dmc>
      <is_fda_regulated_drug>No</is_fda_regulated_drug>
      <is_fda_regulated_device>No</is_fda_regulated_device>
    </oversight_info>
    <brief_summary>
      <textblock>
        This Anchillary project uses a refined technique of ultrasound-guided microneurography of the&#xD;
        human cervical vagus nerve, an approach developed by Professor Vaughan Macefield and used&#xD;
        safely to-date in 44 prior study participants.&#xD;
  &#xD;
        The overall goal of this project is to build upon prior data obtained using this approach by&#xD;
        undertaking a detailed neurophysiological investigation of the human vagus nerve and to&#xD;
        identify the nerve fibers activated during vagal nerve stimulation (VNS) in participants with&#xD;
        implanted VNS devices in response to different stimulation parameters. In addition to&#xD;
        providing data in unprecedented detail into the physiology of the human vagus nerve, this&#xD;
        project will investigate different stimulus intensities, durations and frequencies that&#xD;
        differentially excite myelinated and unmyelinated nerve fibers. These results will inform the&#xD;
        CSP and guide future development of novel neural interfaces for VNS for various clinical&#xD;
        applications.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">October 1, 2023</start_date>
    <completion_date type="Anticipated">October 1, 2024</completion_date>
    <primary_completion_date type="Anticipated">October 1, 2024</primary_completion_date>
    <phase>Phase 1</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Non-Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <primary_purpose>Supportive Care</primary_purpose>
      <masking>None (Open Label)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>identify action potential morphology of specific fibers activated by vagal nerve stimulation (VNS)</measure>
      <time_frame>4 hours</time_frame>
      <description>assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module</description>
    </primary_outcome>
    <primary_outcome>
      <measure>identify ratio of myelinated fibers in specific fibers activated by vagal nerve stimulation (VNS)</measure>
      <time_frame>4 hours</time_frame>
      <description>assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. Whether a nerve fiber is (un)myelinated can be determined by visual inspection. Myelinated fibers typically produce &quot;a positive-going narrow spike profile.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>physiological identification of the specific fibers activated by vagal nerve stimulation (VNS)</measure>
      <time_frame>4 hours</time_frame>
      <description>assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. use of tracing and nerve recordings analysis to identify the types of nerves</description>
    </primary_outcome>
    <primary_outcome>
      <measure>identify firing rates of the specific fibers activated by vagal nerve stimulation (VNS)</measure>
      <time_frame>4 hours</time_frame>
      <description>assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. in Hertz</description>
    </primary_outcome>
    <primary_outcome>
      <measure>identify stimulus current required to activate specific fibers activated by vagal nerve stimulation (VNS)</measure>
      <time_frame>4 hours</time_frame>
      <description>assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. in milli-amps</description>
    </primary_outcome>
    <primary_outcome>
      <measure>differences in firing rates of cardiac parasympathetic vagal activity</measure>
      <time_frame>4 hours</time_frame>
      <description>compare any changes in parasympathetic vagal activity with participants who have not been implanted with a vagal nerve stimulator (Non-VNS Participants).&#xD;
  Labchart; spike histogram module. Unit: Hz.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Discharge variability of cardiac parasympathetic nerve fibers</measure>
      <time_frame>4 hours</time_frame>
      <description>Vagal nerve stimulator device. Coefficient of variation, %</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">60</enrollment>
    <condition>Epilepsy</condition>
    <arm_group>
      <arm_group_label>VNS</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>participants with surgically implanted VNS electrodes to treat drug-resistant epilepsy</description>
    </arm_group>
    <arm_group>
      <arm_group_label>non-VNS participants</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
      <description>participants without implanted VNS devices</description>
    </arm_group>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>VNS stimulation and intraneural recordings</intervention_name>
      <description>A minimum of three stimulation frequencies (1, 10 and 30 Hz), each up to 60s in duration, will be delivered via the VNS device. Intraneural recordings proximal or distal to the VNS electrodes during delivery of VNS will be performed. Approximately two to five fascicles will be explored in each nerve.</description>
      <arm_group_label>VNS</arm_group_label>
    </intervention>
    <intervention>
      <intervention_type>Other</intervention_type>
      <intervention_name>Record multi-unit activity from intraneural sites</intervention_name>
      <description>Perform a more detailed vagal nerve mapping study by recording from single nerve fibers, including those fibers supplying the heart, lungs, airways and other end-organs. The investigators shall perform functional mapping of the left and right vagus nerves, such as those with cardiac-related and/or respiratory-related neural activity. The research team will also record activity from other nearby fibers to map the differences in neurological behavior in fascicles that control the heart, lungs, airways and other systems.</description>
      <arm_group_label>non-VNS participants</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  The participant is greater than or equal to (≥)18 years and is less than or equal to&#xD;
               (≤) 40 years of age&#xD;
  &#xD;
            -  English speaking&#xD;
  &#xD;
            -  Medicare covered or equivalent health insurance from a partner country&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Pregnant&#xD;
  &#xD;
            -  Smokes and is unwilling to abstain from smoking on the day of the experiment.&#xD;
  &#xD;
            -  Inability or unwillingness to provide written informed consent.&#xD;
  &#xD;
            -  Individuals with difficulty standing unassisted for 5 minutes during the tilt-table&#xD;
               testing&#xD;
  &#xD;
            -  Individuals found to have a significant carotid artery plaque or intima-media&#xD;
               thickness &gt; 1 mm as assessed by ultrasonography during the ultrasound-screening steps&#xD;
               of the study visit&#xD;
  &#xD;
            -  Vagus nerve not visible on ultrasound&#xD;
  &#xD;
            -  VNS electrodes are not in a suitable location to allow for microelectrode insertion&#xD;
  &#xD;
            -  Any other clinical reasons deemed by the investigators&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>40 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_official>
      <last_name>Vaughan G Macefield, PhD</last_name>
      <role>Principal Investigator</role>
      <affiliation>Monash University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Kathryn Vera, PhD</last_name>
      <phone>612-625-5018</phone>
      <email>giero002@umn.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>University of Minnesota</name>
        <address>
          <city>Minneapolis</city>
          <state>Minnesota</state>
          <zip>55455</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Kathryn Vera, PhD</last_name>
        <phone>612-625-5018</phone>
        <email>giero002@umn.edu</email>
      </contact>
    </location>
    <location>
      <facility>
        <name>99 Commercial Road</name>
        <address>
          <city>Prahan Victoria</city>
          <zip>3182</zip>
          <country>Australia</country>
        </address>
      </facility>
      <contact>
        <last_name>Mikaela Patros</last_name>
        <email>Mikaela.Patros@baker.edu.au</email>
      </contact>
    </location>
    <location_countries>
      <country>Australia</country>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 10, 2023</study_first_submitted>
    <study_first_submitted_qc>August 28, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 30, 2023</study_first_posted>
    <last_update_submitted>September 13, 2023</last_update_submitted>
    <last_update_submitted_qc>September 13, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 14, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <condition_browse>
      <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
      <mesh_term>Epilepsy</mesh_term>
    </condition_browse>
    <!-- Results have not yet been posted for this study                                          -->
  </clinical_study>
  
  
text: 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/NCT06016686
  org study id: VNS
  nct id: NCT06016686
  lead sponsor: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: No
  This Anchillary project uses a refined technique of ultrasound-guided microneurography of the
        human cervical vagus nerve, an approach developed by Professor Vaughan Macefield and used
        safely to-date in 44 prior study participants.
  
        The overall goal of this project is to build upon prior data obtained using this approach by
        undertaking a detailed neurophysiological investigation of the human vagus nerve and to
        identify the nerve fibers activated during vagal nerve stimulation (VNS) in participants with
        implanted VNS devices in response to different stimulation parameters. In addition to
        providing data in unprecedented detail into the physiology of the human vagus nerve, this
        project will investigate different stimulus intensities, durations and frequencies that
        differentially excite myelinated and unmyelinated nerve fibers. These results will inform the
        CSP and guide future development of novel neural interfaces for VNS for various clinical
        applications.
  allocation: Non-Randomized
  intervention model: Parallel Assignment
  primary purpose: Supportive Care
  masking: None (Open Label)
  measure: identify action potential morphology of specific fibers activated by vagal nerve stimulation (VNS)
  time frame: 4 hours
  description: assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module
  measure: identify ratio of myelinated fibers in specific fibers activated by vagal nerve stimulation (VNS)
  time frame: 4 hours
  description: assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. Whether a nerve fiber is (un)myelinated can be determined by visual inspection. Myelinated fibers typically produce "a positive-going narrow spike profile.
  measure: physiological identification of the specific fibers activated by vagal nerve stimulation (VNS)
  time frame: 4 hours
  description: assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. use of tracing and nerve recordings analysis to identify the types of nerves
  measure: identify firing rates of the specific fibers activated by vagal nerve stimulation (VNS)
  time frame: 4 hours
  description: assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. in Hertz
  measure: identify stimulus current required to activate specific fibers activated by vagal nerve stimulation (VNS)
  time frame: 4 hours
  description: assessing vagal nerve activity in epilepsy participants during and in the absence of stimulation. Labchart; spike histogram module. in milli-amps
  measure: differences in firing rates of cardiac parasympathetic vagal activity
  time frame: 4 hours
  description: compare any changes in parasympathetic vagal activity with participants who have not been implanted with a vagal nerve stimulator (Non-VNS Participants).
  Labchart; spike histogram module. Unit: Hz.
  measure: Discharge variability of cardiac parasympathetic nerve fibers
  time frame: 4 hours
  description: Vagal nerve stimulator device. Coefficient of variation, %
  arm group label: VNS
  arm group type: Experimental
  description: participants with surgically implanted VNS electrodes to treat drug-resistant epilepsy
  arm group label: non-VNS participants
  arm group type: Experimental
  description: participants without implanted VNS devices
  intervention type: Other
  intervention name: VNS stimulation and intraneural recordings
  description: A minimum of three stimulation frequencies (1, 10 and 30 Hz), each up to 60s in duration, will be delivered via the VNS device. Intraneural recordings proximal or distal to the VNS electrodes during delivery of VNS will be performed. Approximately two to five fascicles will be explored in each nerve.
  arm group label: VNS
  intervention type: Other
  intervention name: Record multi-unit activity from intraneural sites
  description: Perform a more detailed vagal nerve mapping study by recording from single nerve fibers, including those fibers supplying the heart, lungs, airways and other end-organs. The investigators shall perform functional mapping of the left and right vagus nerves, such as those with cardiac-related and/or respiratory-related neural activity. The research team will also record activity from other nearby fibers to map the differences in neurological behavior in fascicles that control the heart, lungs, airways and other systems.
  arm group label: non-VNS participants
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 40 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Vaughan G Macefield, PhD
  role: Principal Investigator
  affiliation: Monash University
  last name: Kathryn Vera, PhD
  phone: 612-625-5018
  email: giero002@umn.edu
  facility: 
  contact: 
  facility: 
  contact: 
  country: Australia
  country: United States
  responsible party type: Sponsor
  mesh term: Epilepsy