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/NCT05977946</url>
    </required_header>
    <id_info>
      <org_study_id>5L-BLD-03</org_study_id>
      <secondary_id>23-0265</secondary_id>
      <nct_id>NCT05977946</nct_id>
    </id_info>
    <brief_title>Delivering Transcutaneous Auricular Neurostimulation to Regulate Platelet Activity in Healthy Human Subjects</brief_title>
    <official_title>Delivering Transcutaneous Auricular Neurostimulation to Regulate Platelet Activity in Healthy Human Subjects</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Five Liters, Inc.</agency>
        <agency_class>Industry</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>Northwell Health</agency>
        <agency_class>Other</agency_class>
      </collaborator>
      <collaborator>
        <agency>The Feinstein Institutes for Medical Research</agency>
        <agency_class>Other</agency_class>
      </collaborator>
    </sponsors>
    <source>Spark Biomedical, Inc.</source>
    <oversight_info>
      <has_dmc>No</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>
        This study is designed as a randomized, double-blind, sham-controlled, single-center research&#xD;
        study in which healthy adults will be randomized 1:1 into one of two experimental groups, to&#xD;
        receive transcutaneous auricular vagus nerve stimulation (taVNS) targeting either the&#xD;
        auricular branch of the vagus nerve (ABVN) or tAN, which targets the ABVN and the&#xD;
        auriculotemporal nerve (ATN):&#xD;
  &#xD;
          1. Group 1: Sham taVNS followed by active taVNS&#xD;
  &#xD;
          2. Group 2: Sham tAN followed by active tAN&#xD;
  &#xD;
        Participants will receive 30 minutes of sham stimulation (taVNS or tAN), followed by active&#xD;
        stimulation (taVNS or tAN). Blood biomarkers (local and systemic) will be measured before and&#xD;
        at several timepoints after stimulation to measure the molecular and cellular effects of the&#xD;
        device.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Not yet recruiting</overall_status>
    <start_date type="Anticipated">September 2023</start_date>
    <completion_date type="Anticipated">March 2024</completion_date>
    <primary_completion_date type="Anticipated">March 2024</primary_completion_date>
    <phase>N/A</phase>
    <study_type>Interventional</study_type>
    <has_expanded_access>No</has_expanded_access>
    <study_design_info>
      <allocation>Randomized</allocation>
      <intervention_model>Parallel Assignment</intervention_model>
      <intervention_model_description>Participants will be randomized into two 30-minute stimulation sessions. One session will be active and the other sham. Participants are blinded to treatment group as well as the stimulation session.</intervention_model_description>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Double (Participant, Investigator)</masking>
    </study_design_info>
    <primary_outcome>
      <measure>Biomarker of hemostasis (tissue anti-thrombin (TAT) complex) in blood shed from fingerstick</measure>
      <time_frame>From collection up to 240 minutes, assessed upon receipt of assay results (up to one month)</time_frame>
      <description>Mean TAT levels in shed blood after active stimulation versus sham stimulation within each group</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Biomarker of hemostasis (tissue anti-thrombin (TAT) complex) in blood shed from fingerstick</measure>
      <time_frame>From collection up to 240 minutes, assessed upon receipt of assay results (up to one month)</time_frame>
      <description>Percent change in TAT levels in shed blood after active stimulation between groups (taVNS vs tAN)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Biomarkers of hemostasis (TAT complex, D-dimer, viscoelasticity, coagulation tests (prothrombin time (PT), partial thromboplastin time (PTT)) in circulating blood</measure>
      <time_frame>From collection up to 240 minutes, assessed upon receipt of assay results (up to one month)</time_frame>
      <description>Mean coagulation biomarker levels in circulating blood after active stimulation versus sham stimulation within each group</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Biomarkers of hemostasis (TAT complex, D-dimer, viscoelasticity, coagulation tests (prothrombin time (PT), partial thromboplastin time (PTT)) in circulating blood</measure>
      <time_frame>From collection up to 240 minutes, assessed upon receipt of assay results (up to one month)</time_frame>
      <description>Percent change in coagulation biomarker levels in circulating blood after active stimulation between groups ( taVNS vs tAN)</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Biomarkers of inflammation (tumor necrosis factor (TNF), and interleukin (IL)-1B and IL-6) in circulating whole blood stimulated ex vivo with lipopolysaccharide (LPS)</measure>
      <time_frame>From collection up to 240 minutes, assessed upon receipt of assay results (up to one month)</time_frame>
      <description>Mean inflammation biomarker levels in LPS-stimulated whole blood after active stimulation versus sham stimulation within each group</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Biomarkers of inflammation (tumor necrosis factor (TNF), and interleukin (IL)-1B and IL-6) in circulating whole blood stimulated ex vivo with lipopolysaccharide (LPS)</measure>
      <time_frame>From collection up to 240 minutes, assessed upon receipt of assay results (up to one month)</time_frame>
      <description>Percent change in inflammation biomarker levels in LPS-stimulated whole blood after active stimulation between groups (taVNS vs tAN)</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">30</enrollment>
    <condition>Hemostasis</condition>
    <condition>Blood Biomarkers</condition>
    <arm_group>
      <arm_group_label>Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <arm_group>
      <arm_group_label>Transcutaneous Auricular Neurostimulation (tAN)</arm_group_label>
      <arm_group_type>Experimental</arm_group_type>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Volta System</intervention_name>
      <description>The Volta System is a wearable, battery-operated, neurostimulation system designed to deliver tAN or taVNS. The device will be used to deliver two 30-minute sessions of active or sham therapy according to the participant's randomization group (taVNS or tAN).</description>
      <arm_group_label>Transcutaneous Auricular Neurostimulation (tAN)</arm_group_label>
      <arm_group_label>Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)</arm_group_label>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            1. Participant is between 18 and 65 years of age&#xD;
  &#xD;
            2. Participant is English proficient&#xD;
  &#xD;
            3. Participant is able to provide informed consent and function at an intellectual level&#xD;
               sufficient for study requirements&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            1. Participant has a history of thrombocytopenia (platelet count &lt;100k)&#xD;
  &#xD;
            2. Participant has reported coagulopathy (elevated prothrombin time (PT), elevated&#xD;
               partial thromboplastin time (PTT), elevated activated clotting time (ACT))&#xD;
  &#xD;
            3. Participant has internal bleeding, external bleeding, easy bruising&#xD;
  &#xD;
            4. Participant has a history of abnormal bleeding or blood disorder, including anemia or&#xD;
               anemia-related disorders&#xD;
  &#xD;
            5. Participant has a history of coagulopathy, including hemophilia, stroke, pulmonary&#xD;
               embolism, myocardial infarction, or deep vein thromboses&#xD;
  &#xD;
            6. Participant has a history of conditions that can cause coagulopathic conditions,&#xD;
               including atrial fibrillation, heart valve surgery or replacement, hip or knee&#xD;
               replacement, or clotting disorders&#xD;
  &#xD;
            7. Participants using coagulation- or platelet-modifying therapies such as clotting&#xD;
               factor products, emicizumab, desmopressin acetate, epsilon amino caproic acid, heparin&#xD;
               and its derivatives, argatroban, desirudin, bivalirudin, warfarin, dabigatran,&#xD;
               apixaban, edoxaban, betrixaban, or aspirin&#xD;
  &#xD;
            8. Participant has a history of chronic tobacco use or has ingested nicotine via smoking,&#xD;
               vaping, smokeless tobacco, or nicotine patches in the past three months&#xD;
  &#xD;
            9. Participant has consumed caffeine within the past 12 hours&#xD;
  &#xD;
           10. Participant has received a blood transfusion within 30 days prior to study&#xD;
  &#xD;
           11. Participant has a history of epileptic seizures&#xD;
  &#xD;
           12. Participant has a history of neurologic diseases or traumatic brain injury&#xD;
  &#xD;
           13. Participant has presence of devices (e.g., pacemakers, cochlear prostheses,&#xD;
               neurostimulators)&#xD;
  &#xD;
           14. Participant has abnormal ear anatomy or ear infection present&#xD;
  &#xD;
           15. Women of childbearing potential, not using adequate contraception as per investigator&#xD;
               judgment or not willing to comply with contraception for the duration of the study&#xD;
  &#xD;
           16. Females who are pregnant, lactating or menstruating&#xD;
  &#xD;
           17. Participant has any other significant disease or disorder which, in the opinion of the&#xD;
               Investigator, may either put the participants are risk because of participation in the&#xD;
               trial, or may influence the result of the trial, or the participant's ability to&#xD;
               participate in the trial&#xD;
        </textblock>
      </criteria>
      <gender>All</gender>
      <minimum_age>18 Years</minimum_age>
      <maximum_age>65 Years</maximum_age>
      <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
    </eligibility>
    <overall_contact>
      <last_name>Maaryj Ahmad</last_name>
      <phone>(516) 562-1505</phone>
      <email>mahmad11@northwell.edu</email>
    </overall_contact>
    <location>
      <facility>
        <name>The Feinstein Institutes for Medical Research</name>
        <address>
          <city>Manhasset</city>
          <state>New York</state>
          <zip>11030</zip>
          <country>United States</country>
        </address>
      </facility>
      <contact>
        <last_name>Maaryj Ahmad</last_name>
        <phone>516-562-1505</phone>
        <email>mahmad11@northwell.edu</email>
      </contact>
      <investigator>
        <last_name>Lionel Blanc, PhD</last_name>
        <role>Principal Investigator</role>
      </investigator>
      <investigator>
        <last_name>Jared Huston, MD, FACS</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Carlos Bravos-Iniguez, MD, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
      <investigator>
        <last_name>Julien Papoin, PhD</last_name>
        <role>Sub-Investigator</role>
      </investigator>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>July 14, 2023</study_first_submitted>
    <study_first_submitted_qc>August 2, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">August 7, 2023</study_first_posted>
    <last_update_submitted>September 5, 2023</last_update_submitted>
    <last_update_submitted_qc>September 5, 2023</last_update_submitted_qc>
    <last_update_posted type="Actual">September 6, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Transcutaneous auricular neurostimulation</keyword>
    <keyword>Transcutaneous auricular vagus nerve stimulation</keyword>
    <keyword>Blood biomarkers</keyword>
    <keyword>Neurostimulation</keyword>
    <keyword>Healthy human</keyword>
    <!-- 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/NCT05977946
  org study id: 5L-BLD-03
  secondary id: 23-0265
  nct id: NCT05977946
  lead sponsor: 
  collaborator: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: Yes
  is unapproved device: Yes
  is us export: No
  This study is designed as a randomized, double-blind, sham-controlled, single-center research
        study in which healthy adults will be randomized 1:1 into one of two experimental groups, to
        receive transcutaneous auricular vagus nerve stimulation (taVNS) targeting either the
        auricular branch of the vagus nerve (ABVN) or tAN, which targets the ABVN and the
        auriculotemporal nerve (ATN):
  
          1. Group 1: Sham taVNS followed by active taVNS
  
          2. Group 2: Sham tAN followed by active tAN
  
        Participants will receive 30 minutes of sham stimulation (taVNS or tAN), followed by active
        stimulation (taVNS or tAN). Blood biomarkers (local and systemic) will be measured before and
        at several timepoints after stimulation to measure the molecular and cellular effects of the
        device.
  allocation: Randomized
  intervention model: Parallel Assignment
  intervention model description: Participants will be randomized into two 30-minute stimulation sessions. One session will be active and the other sham. Participants are blinded to treatment group as well as the stimulation session.
  primary purpose: Basic Science
  masking: Double (Participant, Investigator)
  measure: Biomarker of hemostasis (tissue anti-thrombin (TAT) complex) in blood shed from fingerstick
  time frame: From collection up to 240 minutes, assessed upon receipt of assay results (up to one month)
  description: Mean TAT levels in shed blood after active stimulation versus sham stimulation within each group
  measure: Biomarker of hemostasis (tissue anti-thrombin (TAT) complex) in blood shed from fingerstick
  time frame: From collection up to 240 minutes, assessed upon receipt of assay results (up to one month)
  description: Percent change in TAT levels in shed blood after active stimulation between groups (taVNS vs tAN)
  measure: Biomarkers of hemostasis (TAT complex, D-dimer, viscoelasticity, coagulation tests (prothrombin time (PT), partial thromboplastin time (PTT)) in circulating blood
  time frame: From collection up to 240 minutes, assessed upon receipt of assay results (up to one month)
  description: Mean coagulation biomarker levels in circulating blood after active stimulation versus sham stimulation within each group
  measure: Biomarkers of hemostasis (TAT complex, D-dimer, viscoelasticity, coagulation tests (prothrombin time (PT), partial thromboplastin time (PTT)) in circulating blood
  time frame: From collection up to 240 minutes, assessed upon receipt of assay results (up to one month)
  description: Percent change in coagulation biomarker levels in circulating blood after active stimulation between groups ( taVNS vs tAN)
  measure: Biomarkers of inflammation (tumor necrosis factor (TNF), and interleukin (IL)-1B and IL-6) in circulating whole blood stimulated ex vivo with lipopolysaccharide (LPS)
  time frame: From collection up to 240 minutes, assessed upon receipt of assay results (up to one month)
  description: Mean inflammation biomarker levels in LPS-stimulated whole blood after active stimulation versus sham stimulation within each group
  measure: Biomarkers of inflammation (tumor necrosis factor (TNF), and interleukin (IL)-1B and IL-6) in circulating whole blood stimulated ex vivo with lipopolysaccharide (LPS)
  time frame: From collection up to 240 minutes, assessed upon receipt of assay results (up to one month)
  description: Percent change in inflammation biomarker levels in LPS-stimulated whole blood after active stimulation between groups (taVNS vs tAN)
  arm group label: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)
  arm group type: Experimental
  arm group label: Transcutaneous Auricular Neurostimulation (tAN)
  arm group type: Experimental
  intervention type: Device
  intervention name: Volta System
  description: The Volta System is a wearable, battery-operated, neurostimulation system designed to deliver tAN or taVNS. The device will be used to deliver two 30-minute sessions of active or sham therapy according to the participant's randomization group (taVNS or tAN).
  arm group label: Transcutaneous Auricular Neurostimulation (tAN)
  arm group label: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS)
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 65 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Maaryj Ahmad
  phone: (516) 562-1505
  email: mahmad11@northwell.edu
  facility: 
  contact: 
  investigator: 
  investigator: 
  investigator: 
  investigator: 
  country: United States
  responsible party type: Sponsor