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/NCT06034496</url>
    </required_header>
    <id_info>
      <org_study_id>STUDY00003572</org_study_id>
      <nct_id>NCT06034496</nct_id>
    </id_info>
    <brief_title>Cranial Electrotherapy Stimulation and Acute Stress</brief_title>
    <official_title>Cranial Electrotherapy Stimulation (CES) Influences on Acute Stress Responses</official_title>
    <sponsors>
      <lead_sponsor>
        <agency>Tufts University</agency>
        <agency_class>Other</agency_class>
      </lead_sponsor>
      <collaborator>
        <agency>United States Department of Defense</agency>
        <agency_class>U.S. Fed</agency_class>
      </collaborator>
    </sponsors>
    <source>Tufts University</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_us_export>No</is_us_export>
    </oversight_info>
    <brief_summary>
      <textblock>
        The goal of this study is to quantify the effects of 20 sessions of Cranial Electrotherapy&#xD;
        Stimulation (CES) on measures of acute stress responses in Soldiers. The main question it&#xD;
        aims to answer is how 20 sessions of CES will affect Soldiers' biochemical (salivary alpha&#xD;
        amylase and cortisol), physiological (e.g., heart rate, heart rate variability, respiration&#xD;
        rate), emotional (state anxiety), and behavioral (i.e., cognitive task performance)&#xD;
        responses.&#xD;
  &#xD;
          -  On Day 1, participants will complete a baseline measure assessing their biochemical,&#xD;
             physiological, emotional, and behavioral responses to a stressful lethal force decision&#xD;
             making task.&#xD;
  &#xD;
          -  In the next four to six weeks, participants will complete 20 CES sessions.&#xD;
  &#xD;
          -  Within five days of completing the 20 CES sessions, participants will complete a&#xD;
             follow-up measure assessing their biochemical, physiological, emotional, and behavioral&#xD;
             responses to the same stressful lethal force decision making task they completed on Day&#xD;
             1.&#xD;
  &#xD;
        Researchers will compare the Active CES group to the Sham CES group to see how 20 sessions of&#xD;
        Active CES will affect the participants responses to their biochemical, physiological,&#xD;
        emotional and behavioral responses relative to the Sham CES group.&#xD;
      </textblock>
    </brief_summary>
    <overall_status>Recruiting</overall_status>
    <start_date type="Anticipated">September 13, 2023</start_date>
    <completion_date type="Anticipated">July 2025</completion_date>
    <primary_completion_date type="Anticipated">July 2025</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>
      <primary_purpose>Basic Science</primary_purpose>
      <masking>Triple (Participant, Care Provider, Investigator)</masking>
      <masking_description>Coded devices with master key kept outside of research team.</masking_description>
    </study_design_info>
    <primary_outcome>
      <measure>Change from baseline in heart rate during stressful lethal force decision making task</measure>
      <time_frame>Baseline and follow-up session after 20 CES to be completed within 4-6weeks</time_frame>
      <description>heart rate will be measured in beats per minute.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in respiration rate during stressful lethal force decision making task</measure>
      <time_frame>Baseline and follow-up session after 20 CES to be completed within 4-6weeks</time_frame>
      <description>respiration rate will be measured in breaths per minute.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in heart rate variability during stressful lethal force decision making task</measure>
      <time_frame>Baseline and follow-up session after 20 CES to be completed within 4-6weeks</time_frame>
      <description>Heart rate variability will be measured in RMSSD.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change over time in alpha amylase during stressful lethal force decision making task</measure>
      <time_frame>Baseline and follow-up session after 20 CES completed within 4-6weeks</time_frame>
      <description>Alpha amylase (IU) will be measured through saliva samples. Saliva samples will be taken at five time points, approximately 20 minute increments during the baseline and follow-up sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change over time in cortisol during stressful lethal force decision making task</measure>
      <time_frame>Baseline and follow-up session after 20 CES completed within 4-6weeks</time_frame>
      <description>Cortisol (ng/dL) will be measured through saliva samples. Saliva samples will be taken at five time points, approximately 20 minute increments during the baseline and follow-up sessions.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change over time in State Trait Anxiety Inventory (STAI) scores at each session (including CES sessions) from baseline to follow-up</measure>
      <time_frame>At baseline, at each of the 20 CES sessions completed within 4-6weeks, and at follow-up to be completed within 5 days of last CES</time_frame>
      <description>STAI assesses both state and trait anxiety separately with each scale ranging from 20 to 80, with higher scores correlating with greater anxiety.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in recognition memory</measure>
      <time_frame>Baseline and follow-up session after 20 CES completed within 4-6weeks</time_frame>
      <description>Recognition memory of previously learned targets while ignoring visually similar distractor objects will be measured and evaluated with d prime scores. Higher d prime scores correlate with more accurate responses.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in spatial orientation</measure>
      <time_frame>Baseline and follow-up session after 20 CES completed within 4-6weeks</time_frame>
      <description>Spatial orientation task will involve pointing towards a series of distant (out of visible range) landmarks in the virtual environment and estimating distance to those landmarks. Spatial orientation will be calculated using mean absolute angular error. Larger numbers correlate with higher error.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in decision making accuracy</measure>
      <time_frame>Baseline and follow-up session after 20 CES completed within 4-6weeks</time_frame>
      <description>Participants will make lethal force decision making by shooting at threatening targets and allowing non-threatening targets to pass. Decision making accuracy will be calculated using d prime. Higher d prime correlates with better accuracy.</description>
    </primary_outcome>
    <primary_outcome>
      <measure>Change from baseline in decision making reaction time</measure>
      <time_frame>Baseline and follow-up session after 20 CES completed within 4-6weeks</time_frame>
      <description>Participants will make lethal force decision making by shooting at threatening targets and allowing non-threatening targets to pass. Decision making reaction time to shoot at threatening targets will be measured in milliseconds.</description>
    </primary_outcome>
    <number_of_arms>2</number_of_arms>
    <enrollment type="Anticipated">200</enrollment>
    <condition>Anxiety State</condition>
    <arm_group>
      <arm_group_label>Active CES</arm_group_label>
      <arm_group_type>Active Comparator</arm_group_type>
      <description>Active Cranial Electrotherapy Stimulation (CES)</description>
    </arm_group>
    <arm_group>
      <arm_group_label>Sham CES</arm_group_label>
      <arm_group_type>Sham Comparator</arm_group_type>
      <description>Sham Cranial Electrotherapy Stimulation (CES)</description>
    </arm_group>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Active CES</intervention_name>
      <description>Active CES group will receive a minimum of 250µA and up to 500µA depending on thresholding, once daily for 20 days (over the course of 4~6 weeks), 20 minutes per day.</description>
      <arm_group_label>Active CES</arm_group_label>
      <other_name>Alpha-Stim</other_name>
    </intervention>
    <intervention>
      <intervention_type>Device</intervention_type>
      <intervention_name>Sham CES</intervention_name>
      <description>Sham CES group will be identical to Active CES group with the exception of the device not administering any electrical current</description>
      <arm_group_label>Sham CES</arm_group_label>
      <other_name>Alpha-Stim</other_name>
    </intervention>
    <eligibility>
      <criteria>
        <textblock>
          Inclusion Criteria:&#xD;
  &#xD;
            -  18-40 years of age (17-40 if emancipated minor)&#xD;
  &#xD;
            -  Can sit and stand freely.&#xD;
  &#xD;
            -  Have not used or experienced CES administration in the past.&#xD;
  &#xD;
            -  Agree to have their data stored in a repository (database) for future use.&#xD;
  &#xD;
          Exclusion Criteria:&#xD;
  &#xD;
            -  Use of prescription medications, other than oral contraceptives&#xD;
  &#xD;
            -  Women only:&#xD;
  &#xD;
                 1. Pregnant or plan to become pregnant during the study&#xD;
  &#xD;
                 2. Nursing&#xD;
  &#xD;
            -  History of:&#xD;
  &#xD;
                 1. A neurological or psychological disorder (such as depression, anxiety disorders,&#xD;
                    migraines, cluster headaches, seizures, Post-traumatic stress disorder (PTSD) or&#xD;
                    panic attacks).&#xD;
  &#xD;
                 2. Cardiac disease (including arrhythmia or fast or skipped heart beats).&#xD;
  &#xD;
                 3. Implanted medical devices, such as pacemakers.&#xD;
  &#xD;
                 4. Hypertension.&#xD;
  &#xD;
                 5. Insomnia&#xD;
  &#xD;
                 6. Head injury (including neurosurgery, concussion, TBI, skull fracture, hematoma)&#xD;
  &#xD;
                 7. Illness that caused brain injury&#xD;
  &#xD;
                 8. Any other brain-related condition (such as traumatic brain injury)&#xD;
  &#xD;
                 9. Metal in the head (outside of mouth, such as shrapnel, surgical clips, or&#xD;
                    fragments from welding or metalwork)&#xD;
  &#xD;
                10. Implanted medical device (e.g., pacemaker, insulin pump)&#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>Kana Okano, Ph.D.</last_name>
      <role>Principal Investigator</role>
      <affiliation>Tufts University</affiliation>
    </overall_official>
    <overall_contact>
      <last_name>Kana Okano, Ph.D.</last_name>
      <phone>(617) 627-1059</phone>
      <email>kana.okano@tufts.edu</email>
    </overall_contact>
    <overall_contact_backup>
      <last_name>Tad Brunye, Ph.D.</last_name>
      <phone>(508) 206-3841</phone>
      <email>tbruny01@tufts.edu</email>
    </overall_contact_backup>
    <location>
      <facility>
        <name>Tufts University</name>
        <address>
          <city>Medford</city>
          <state>Massachusetts</state>
          <zip>02155</zip>
          <country>United States</country>
        </address>
      </facility>
      <status>Recruiting</status>
      <contact>
        <last_name>Sue Grodberg, M.A.</last_name>
        <phone>617-627-1059</phone>
        <email>sue.grodberg@tufts.edu</email>
      </contact>
    </location>
    <location_countries>
      <country>United States</country>
    </location_countries>
    <verification_date>September 2023</verification_date>
    <study_first_submitted>August 18, 2023</study_first_submitted>
    <study_first_submitted_qc>September 5, 2023</study_first_submitted_qc>
    <study_first_posted type="Actual">September 13, 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 13, 2023</last_update_posted>
    <responsible_party>
      <responsible_party_type>Sponsor</responsible_party_type>
    </responsible_party>
    <keyword>Cranial Electrotherapy Stimulation</keyword>
    <keyword>Acute Stress</keyword>
    <patient_data>
      <sharing_ipd>Undecided</sharing_ipd>
      <ipd_description>Participants consent to having their deidentified data placed in a repository/shared upon protocol closure, however it is not mandated by the protocol or institution.</ipd_description>
    </patient_data>
    <provided_document_section>
      <provided_document>
        <document_type>Study Protocol</document_type>
        <document_has_protocol>Yes</document_has_protocol>
        <document_has_icf>No</document_has_icf>
        <document_has_sap>No</document_has_sap>
        <document_date>April 19, 2023</document_date>
        <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT06034496/Prot_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>April 19, 2023</document_date>
        <document_url>https://ClinicalTrials.gov/ProvidedDocs/96/NCT06034496/ICF_001.pdf</document_url>
      </provided_document>
    </provided_document_section>
    <!-- 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/NCT06034496
  org study id: STUDY00003572
  nct id: NCT06034496
  lead sponsor: 
  collaborator: 
  has dmc: No
  is fda regulated drug: No
  is fda regulated device: Yes
  is us export: No
  The goal of this study is to quantify the effects of 20 sessions of Cranial Electrotherapy
        Stimulation (CES) on measures of acute stress responses in Soldiers. The main question it
        aims to answer is how 20 sessions of CES will affect Soldiers' biochemical (salivary alpha
        amylase and cortisol), physiological (e.g., heart rate, heart rate variability, respiration
        rate), emotional (state anxiety), and behavioral (i.e., cognitive task performance)
        responses.
  
          -  On Day 1, participants will complete a baseline measure assessing their biochemical,
             physiological, emotional, and behavioral responses to a stressful lethal force decision
             making task.
  
          -  In the next four to six weeks, participants will complete 20 CES sessions.
  
          -  Within five days of completing the 20 CES sessions, participants will complete a
             follow-up measure assessing their biochemical, physiological, emotional, and behavioral
             responses to the same stressful lethal force decision making task they completed on Day
             1.
  
        Researchers will compare the Active CES group to the Sham CES group to see how 20 sessions of
        Active CES will affect the participants responses to their biochemical, physiological,
        emotional and behavioral responses relative to the Sham CES group.
  allocation: Randomized
  intervention model: Parallel Assignment
  primary purpose: Basic Science
  masking: Triple (Participant, Care Provider, Investigator)
  masking description: Coded devices with master key kept outside of research team.
  measure: Change from baseline in heart rate during stressful lethal force decision making task
  time frame: Baseline and follow-up session after 20 CES to be completed within 4-6weeks
  description: heart rate will be measured in beats per minute.
  measure: Change from baseline in respiration rate during stressful lethal force decision making task
  time frame: Baseline and follow-up session after 20 CES to be completed within 4-6weeks
  description: respiration rate will be measured in breaths per minute.
  measure: Change from baseline in heart rate variability during stressful lethal force decision making task
  time frame: Baseline and follow-up session after 20 CES to be completed within 4-6weeks
  description: Heart rate variability will be measured in RMSSD.
  measure: Change over time in alpha amylase during stressful lethal force decision making task
  time frame: Baseline and follow-up session after 20 CES completed within 4-6weeks
  description: Alpha amylase (IU) will be measured through saliva samples. Saliva samples will be taken at five time points, approximately 20 minute increments during the baseline and follow-up sessions.
  measure: Change over time in cortisol during stressful lethal force decision making task
  time frame: Baseline and follow-up session after 20 CES completed within 4-6weeks
  description: Cortisol (ng/dL) will be measured through saliva samples. Saliva samples will be taken at five time points, approximately 20 minute increments during the baseline and follow-up sessions.
  measure: Change over time in State Trait Anxiety Inventory (STAI) scores at each session (including CES sessions) from baseline to follow-up
  time frame: At baseline, at each of the 20 CES sessions completed within 4-6weeks, and at follow-up to be completed within 5 days of last CES
  description: STAI assesses both state and trait anxiety separately with each scale ranging from 20 to 80, with higher scores correlating with greater anxiety.
  measure: Change from baseline in recognition memory
  time frame: Baseline and follow-up session after 20 CES completed within 4-6weeks
  description: Recognition memory of previously learned targets while ignoring visually similar distractor objects will be measured and evaluated with d prime scores. Higher d prime scores correlate with more accurate responses.
  measure: Change from baseline in spatial orientation
  time frame: Baseline and follow-up session after 20 CES completed within 4-6weeks
  description: Spatial orientation task will involve pointing towards a series of distant (out of visible range) landmarks in the virtual environment and estimating distance to those landmarks. Spatial orientation will be calculated using mean absolute angular error. Larger numbers correlate with higher error.
  measure: Change from baseline in decision making accuracy
  time frame: Baseline and follow-up session after 20 CES completed within 4-6weeks
  description: Participants will make lethal force decision making by shooting at threatening targets and allowing non-threatening targets to pass. Decision making accuracy will be calculated using d prime. Higher d prime correlates with better accuracy.
  measure: Change from baseline in decision making reaction time
  time frame: Baseline and follow-up session after 20 CES completed within 4-6weeks
  description: Participants will make lethal force decision making by shooting at threatening targets and allowing non-threatening targets to pass. Decision making reaction time to shoot at threatening targets will be measured in milliseconds.
  arm group label: Active CES
  arm group type: Active Comparator
  description: Active Cranial Electrotherapy Stimulation (CES)
  arm group label: Sham CES
  arm group type: Sham Comparator
  description: Sham Cranial Electrotherapy Stimulation (CES)
  intervention type: Device
  intervention name: Active CES
  description: Active CES group will receive a minimum of 250µA and up to 500µA depending on thresholding, once daily for 20 days (over the course of 4~6 weeks), 20 minutes per day.
  arm group label: Active CES
  other name: Alpha-Stim
  intervention type: Device
  intervention name: Sham CES
  description: Sham CES group will be identical to Active CES group with the exception of the device not administering any electrical current
  arm group label: Sham CES
  other name: Alpha-Stim
  criteria: 
  gender: All
  minimum age: 18 Years
  maximum age: 40 Years
  healthy volunteers: Accepts Healthy Volunteers
  last name: Kana Okano, Ph.D.
  role: Principal Investigator
  affiliation: Tufts University
  last name: Kana Okano, Ph.D.
  phone: (617) 627-1059
  email: kana.okano@tufts.edu
  last name: Tad Brunye, Ph.D.
  phone: (508) 206-3841
  email: tbruny01@tufts.edu
  facility: 
  status: Recruiting
  contact: 
  country: United States
  responsible party type: Sponsor
  sharing ipd: Undecided
  ipd description: Participants consent to having their deidentified data placed in a repository/shared upon protocol closure, however it is not mandated by the protocol or institution.
  provided document: 
  provided document: 