<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/NCT04448990</url>
  </required_header>
  <id_info>
    <org_study_id>BB 196/18</org_study_id>
    <nct_id>NCT04448990</nct_id>
  </id_info>
  <brief_title>Antinociceptive Effect of Transauricular Electrical Vagal Nerve Stimulation</brief_title>
  <acronym>TVNS_TSP</acronym>
  <official_title>Antinociceptive Effect of Transauricular Electrical Vagal Nerve Stimulation and Its Underlying Mechanisms</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University Medicine Greifswald</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University Medicine Greifswald</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 investigation is going to study whether electrical tVNS applied at the cymba of&#xD;
      auricular conchae reduces central sensitization of experimentally induced pain in comparison&#xD;
      with electrical sham stimulation applied at the earlobes and whether the hypoalgesic effects&#xD;
      of tVNS disappear after pharmacological block of muscarinic receptors. Also, this&#xD;
      investigation will examine whether tVNS is associated with activation in brain areas,&#xD;
      involved in processing of thermal pain stimuli and emotional and vegetative modulation of&#xD;
      thermal pain in subjects who will respond with antinociceptive reaction to tVNS.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Not yet recruiting</last_known_status>
  <start_date type="Anticipated">May 2021</start_date>
  <completion_date type="Anticipated">August 2023</completion_date>
  <primary_completion_date type="Anticipated">April 2023</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>Crossover Assignment</intervention_model>
    <intervention_model_description>Two periods (real and sham tVNS) randomized crossover investigation in healthy volunteers</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>Real tVNS will be applied using pre-defined characteristics of tVNS device to cymba conchae of the auricle, sham procedure will be the same, however applied to tubule of the auricle</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Unpleasantness of pain</measure>
    <time_frame>Continuously 5 minutes during the experimental heat pain stimulation</time_frame>
    <description>perceived unpleasantness of pain, which participants will rate continuously during the repetitive heat stimulation using a computerized visual analogue scale (CoVAS, Medoc Advanced Medical Systems, Ramat Yishai, Israel) ranging from 0 (= not unpleasant at all) to 100 (= intolerable pain).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Heart rate</measure>
    <time_frame>Continuously 5 minutes during the experimental heat pain stimulation</time_frame>
    <description>Heart rate (bpm)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Blood pressure</measure>
    <time_frame>4 times during 5 minutes of the experimental heat pain stimulation</time_frame>
    <description>Systolic and diastolic blood pressure</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">66</enrollment>
  <condition>Pain, Acute</condition>
  <arm_group>
    <arm_group_label>tVNS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Stimulation will be applied using TENS device eco 2 (Schwa-Medico, Pierenkemper GmbH, Ehringshausen, Germany) bilaterally at the cymba conchae of the auricles for 20 minutes. Current intensity (1-max. 10 mA) will be individually adjusted for each ear separately until the maximal tVNS intensity, which is not uncomfortable or painful, will be achieved.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Same stimulation will be applied using TENS device eco 2 (Schwa-Medico, Pierenkemper GmbH, Ehringshausen, Germany) to bilaterally to the earlobes for 20 minutes. Current intensity (1-max. 10 mA) will be individually adjusted for each ear separately until the maximal tVNS intensity, which is not uncomfortable or painful, will be achieved.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>TENS eco 2 Transauricular vagal nerve stimulation</intervention_name>
    <description>Auricular electrical stimulation will be applied bilaterally using Transcutaneous Electrical Nerve Stimulation device TENS eco 2 (Schwa-Medico, Pierenkemper GmbH, Ehringshausen, Germany).&#xD;
tVNS will be applied bilaterally using electrical square impulses delivered in blocks of 9 impulses with a frequency of 100 Hz and a pulse width of 200 μs emitted twice per second resulting in mixed frequency pattern of 100 Hz/2 Hz with the current intensity, that will be individually adjusted for each ear separately until the maximal tVNS intensity, which is not uncomfortable or painful, will be achieved.</description>
    <arm_group_label>tVNS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham TENS eco 2</intervention_name>
    <description>Sham</description>
    <arm_group_label>Sham</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  healthy volunteers aged 18-45 years old, who have given informed consent&#xD;
&#xD;
          -  at least two days free from consume of recreational drugs&#xD;
&#xD;
          -  no local infection at the site of tVNS and pain stimulation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  psychiatric disorders&#xD;
&#xD;
          -  abnormal skin conditions (infection, scars, psoriasis, eczema) at the site of tVNS&#xD;
&#xD;
          -  contra-indications for MRI (e.g. claustrophobia, pregnancy, tattoos, metallic&#xD;
             implants)&#xD;
&#xD;
          -  history of coronary heart disease, cardiac arrhythmia, glaucoma, allergy to sulphates&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>19 Years</minimum_age>
    <maximum_age>40 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Taras Usichenko, MD, PhD</last_name>
    <phone>+49 3834865893</phone>
    <email>taras@uni-greifswald.de</email>
  </overall_contact>
  <location>
    <facility>
      <name>University Medicine of Greifswald</name>
      <address>
        <city>Greifswald</city>
        <zip>17475</zip>
        <country>Germany</country>
      </address>
    </facility>
    <contact>
      <last_name>Taras Usichenko, MD, PhD</last_name>
      <email>taras@uni-greifswald.de</email>
    </contact>
  </location>
  <location_countries>
    <country>Germany</country>
  </location_countries>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 23, 2020</study_first_submitted>
  <study_first_submitted_qc>June 25, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 26, 2020</study_first_posted>
  <last_update_submitted>June 25, 2020</last_update_submitted>
  <last_update_submitted_qc>June 25, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 26, 2020</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>Acute Pain</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
    <ipd_description>Data will be available of request</ipd_description>
  </patient_data>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04448990
org study id: BB 196/18
nct id: NCT04448990
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
This investigation is going to study whether electrical tVNS applied at the cymba of
      auricular conchae reduces central sensitization of experimentally induced pain in comparison
      with electrical sham stimulation applied at the earlobes and whether the hypoalgesic effects
      of tVNS disappear after pharmacological block of muscarinic receptors. Also, this
      investigation will examine whether tVNS is associated with activation in brain areas,
      involved in processing of thermal pain stimuli and emotional and vegetative modulation of
      thermal pain in subjects who will respond with antinociceptive reaction to tVNS.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Two periods (real and sham tVNS) randomized crossover investigation in healthy volunteers
primary purpose: Basic Science
masking: Double (Participant, Outcomes Assessor)
masking description: Real tVNS will be applied using pre-defined characteristics of tVNS device to cymba conchae of the auricle, sham procedure will be the same, however applied to tubule of the auricle
measure: Unpleasantness of pain
time frame: Continuously 5 minutes during the experimental heat pain stimulation
description: perceived unpleasantness of pain, which participants will rate continuously during the repetitive heat stimulation using a computerized visual analogue scale (CoVAS, Medoc Advanced Medical Systems, Ramat Yishai, Israel) ranging from 0 (= not unpleasant at all) to 100 (= intolerable pain).
measure: Heart rate
time frame: Continuously 5 minutes during the experimental heat pain stimulation
description: Heart rate (bpm)
measure: Blood pressure
time frame: 4 times during 5 minutes of the experimental heat pain stimulation
description: Systolic and diastolic blood pressure
arm group label: tVNS
arm group type: Experimental
description: Stimulation will be applied using TENS device eco 2 (Schwa-Medico, Pierenkemper GmbH, Ehringshausen, Germany) bilaterally at the cymba conchae of the auricles for 20 minutes. Current intensity (1-max. 10 mA) will be individually adjusted for each ear separately until the maximal tVNS intensity, which is not uncomfortable or painful, will be achieved.
arm group label: Sham
arm group type: Sham Comparator
description: Same stimulation will be applied using TENS device eco 2 (Schwa-Medico, Pierenkemper GmbH, Ehringshausen, Germany) to bilaterally to the earlobes for 20 minutes. Current intensity (1-max. 10 mA) will be individually adjusted for each ear separately until the maximal tVNS intensity, which is not uncomfortable or painful, will be achieved.
intervention type: Device
intervention name: TENS eco 2 Transauricular vagal nerve stimulation
description: Auricular electrical stimulation will be applied bilaterally using Transcutaneous Electrical Nerve Stimulation device TENS eco 2 (Schwa-Medico, Pierenkemper GmbH, Ehringshausen, Germany).
tVNS will be applied bilaterally using electrical square impulses delivered in blocks of 9 impulses with a frequency of 100 Hz and a pulse width of 200 μs emitted twice per second resulting in mixed frequency pattern of 100 Hz/2 Hz with the current intensity, that will be individually adjusted for each ear separately until the maximal tVNS intensity, which is not uncomfortable or painful, will be achieved.
arm group label: tVNS
intervention type: Device
intervention name: Sham TENS eco 2
description: Sham
arm group label: Sham
criteria: 
gender: All
minimum age: 19 Years
maximum age: 40 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Taras Usichenko, MD, PhD
phone: +49 3834865893
email: taras@uni-greifswald.de
facility: 
contact: 
country: Germany
responsible party type: Sponsor
mesh term: Acute Pain
sharing ipd: Undecided
ipd description: Data will be available of request