<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/NCT04474015</url>
  </required_header>
  <id_info>
    <org_study_id>WRAIR #1927</org_study_id>
    <nct_id>NCT04474015</nct_id>
  </id_info>
  <brief_title>Optimizing Volunteer Comfort for Transcranial Electrical Stimulation (TES): An Assessment</brief_title>
  <acronym>TES</acronym>
  <official_title>Optimizing Volunteer Comfort for Transcranial Electrical Stimulation (TES): An Assessment of Sensor (Electrode) Preparations - PARTS A, B and C</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>U.S. Army Medical Research and Development Command</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Walter Reed Army Institute of Research (WRAIR)</agency>
      <agency_class>U.S. Fed</agency_class>
    </collaborator>
  </sponsors>
  <source>Walter Reed Army Institute of Research (WRAIR)</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>
      Transcranial electrical stimulation (TES) utilizing weak electrical fields (&lt;5 milliamps of&#xD;
      current - as proposed in the present pilot study) is an extremely safe therapeutic technique&#xD;
      in use for over 40 years. During that time, TES has never been associated with a serious&#xD;
      adverse event in a research setting nor a serious reported adverse event in a clinical&#xD;
      setting. The main side effect associated with TES is irritation of the skin beneath the&#xD;
      electrodes (as is commonly found from similar preparations used for polysomnography). The&#xD;
      purpose of this pilot study is to identify the type of electrode preparation that maximizes&#xD;
      subject comfort during transdermal/transcranial electrical stimulation (TES) using the&#xD;
      NeuroConn DC Plus Stimulator.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study, volunteers will be divided into groups based on the nature of the stimulation&#xD;
      waveform utilized (DC 0.75 Hz, modified AC 0.75 Hz, AC sinusoidal 3.0 Hz or pulsed&#xD;
      stimulation of up to 500 ms duration). These waveforms were chosen based on the physiology of&#xD;
      slow-wave sleep (SWS). Ultimately, the goal is to use TES during sleep to enhance the&#xD;
      slow-wave activity (SWA) of sleep. Slow-wave sleep is characterized by two main frequency&#xD;
      bands with differing underlying physiologies: (1) slow oscillation activity with a peak of&#xD;
      0.75 Hz, and (2) delta activity with a peak of approximately 3.0 Hz. Therefore, in future&#xD;
      studies, the plan is to stimulate at one or both of these frequencies. The endogenous slow&#xD;
      activity of the brain consists of electrical fields of &quot;alternating current&quot; with periods of&#xD;
      relative cellular depolarization and periods of relative cellular hyperpolarization. The goal&#xD;
      is to enhance this endogenous behavior with transcranial electrical stimulation at the two&#xD;
      major slow- wave frequencies (0.75 Hz, 3.0 Hz), or using a pulsed stimulation paradigm to&#xD;
      induce slow wave activity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Enrolling by invitation</overall_status>
  <start_date type="Actual">May 24, 2014</start_date>
  <completion_date type="Anticipated">February 12, 2026</completion_date>
  <primary_completion_date type="Anticipated">February 12, 2024</primary_completion_date>
  <phase>N/A</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>
    <intervention_model_description>Groups A, B and C are run sequentially.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Sensation scale</measure>
    <time_frame>Day 1</time_frame>
    <description>participants indicate level of sensation on a scale from 1-10; Sensation Scale: 0 to 10 where 10 indicates experiencing severe discomfort; 0 indicates no discomfort</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Erythema observation</measure>
    <time_frame>Day 1</time_frame>
    <description>observation of skin erythema following removal of electrodes: At baseline observation for presence of skin lesions/pathology; following stimulation observation of a change or no change in skin lesions/pathology from baseline</description>
  </primary_outcome>
  <number_of_arms>7</number_of_arms>
  <enrollment type="Anticipated">75</enrollment>
  <condition>Performance Enhancing Product Use</condition>
  <condition>Sleep</condition>
  <arm_group>
    <arm_group_label>Part A, Group 1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Forearm stimulation during wake (study PART A) - electrode placement = volar surface of forearm, 2 electrodes (cathode and anode): Group 1 will receive forearm stimulation at 0.75 Hz with an oscillating direct current (DC) waveform while awake.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A, Group 2</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Forearm stimulation during wake (study PART A) - electrode placement = volar surface of forearm, 2 electrodes (cathode and anode): Group 2 will receive forearm stimulation at 0.75 Hz with a modified alternating current (AC) waveform while awake.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part A, Group 3</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Forearm stimulation during wake (study PART A) - electrode placement = volar surface of forearm, 2 electrodes (cathode and anode): Group 3 will receive forearm stimulation at 3.0 Hz with an alternating current (AC) sinusoidal waveform while awake.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B, Group 4</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Scalp stimulation during sleep (study PART B) - bilateral electrode pairs placed on the upper forehead near the midline (F3 and F4) and adjacent to the ear in the mastoid region (M1 and M2). roup 4 will receive scalp stimulation at 0.75 Hz with an oscillating direct current (DC) waveform during sleep.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B, Group 5</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Scalp stimulation during sleep (study PART B) - bilateral electrode pairs placed on the upper forehead near the midline (F3 and F4) and adjacent to the ear in the mastoid region (M1 and M2). Group 5 will receive scalp stimulation at 0.75 Hz with a modified alternating current (AC) waveform during sleep.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part B, Group 6</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Scalp stimulation during sleep (study PART B) - bilateral electrode pairs placed on the upper forehead near the midline (F3 and F4) and adjacent to the ear in the mastoid region (M1 and M2). Group 6 will receive scalp stimulation at 3.0 Hz with an alternating current (AC) sinusoidal waveform during sleep.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Part C, Group 7</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Pulsed Stimulation: Group 7 (Part C)will receive a series of brief stimulations of up to 500 millisecond duration and of up to 5 milliamperes of current, using either metal electrodes or sponge electrodes as stimulating electrodes.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>transcranial electric stimulation</intervention_name>
    <description>NeuroConn® DC Plus stimulator: the NeuroConn® stimulator can be programmed with specific frequencies of stimulation ranging from 0.5 to 500 Hz. This device is therefore appropriate for the present study to stimulate only at 0.75 or 3.0 Hz. Also, the NeuroConn only allows low current intensities to be chosen. The maximum current intensity that can be delivered with this stimulator is 5 milliamps.</description>
    <arm_group_label>Part A, Group 1</arm_group_label>
    <arm_group_label>Part A, Group 2</arm_group_label>
    <arm_group_label>Part A, Group 3</arm_group_label>
    <arm_group_label>Part B, Group 4</arm_group_label>
    <arm_group_label>Part B, Group 5</arm_group_label>
    <arm_group_label>Part B, Group 6</arm_group_label>
    <arm_group_label>Part C, Group 7</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria - healthy adult men and non-pregnant, non-lactating women aged 18-39&#xD;
        years, inclusive.&#xD;
&#xD;
        Exclusion criteria - The following exclusion criteria apply to all volunteers, are&#xD;
        consistent with those used in our other sleep studies, and are applied in this protocol in&#xD;
        order to obtain a sample of volunteers who are likely to be representative of future study&#xD;
        populations:&#xD;
&#xD;
          -  Self-reported habitual nightly sleep amounts outside the target range of 6-9 hours&#xD;
             (i.e., less than 6 hours per night or more than 9 hours per night, on average):&#xD;
&#xD;
          -  Nighttime lights-out times earlier than 2100 hours on average during weeknights&#xD;
             (Sunday through Thursday) for the past month&#xD;
&#xD;
          -  Morning wake-up times later than 0900 on average during weekdays (Monday through&#xD;
             Friday) for the past month.&#xD;
&#xD;
          -  History of cardiovascular disease (to include but not limited to arrhythmias, valvular&#xD;
             heart disease, congestive heart failure, history of sudden cardiac death or myocardial&#xD;
             infarction)&#xD;
&#xD;
          -  Reported habitual napping (&gt; 3 times a week in conjunction with normal sleep habits)&#xD;
&#xD;
          -  Resting blood pressure above 140/90&#xD;
&#xD;
          -  Resting pulse &gt; 110&#xD;
&#xD;
          -  Neurologic disorder (to include but not limited to epilepsy or another seizure&#xD;
             disorder, amnesia for any reason, hydrocephalus, MS, narcolepsy or other sleep&#xD;
             disorders)&#xD;
&#xD;
          -  Kidney disease&#xD;
&#xD;
          -  History of psychiatric disorder requiring hospitalization or psychiatric medication&#xD;
             for any length of time&#xD;
&#xD;
          -  Beck Depression Inventory score of 14 or above&#xD;
&#xD;
          -  Underlying pulmonary disease requiring daily inhaler use&#xD;
&#xD;
          -  Regular nicotine use (or addiction) (defined as more than 1 cigarette or equivalent&#xD;
             per week) within the last 1 year&#xD;
&#xD;
          -  Positive nicotine/cotinine screen as determined by NicCheck™ I test strips&#xD;
&#xD;
          -  Heavy alcohol use to be determined by the PI or his/her representative (minimum limit&#xD;
             to define heavy alcohol use is 14 drinks per week)&#xD;
&#xD;
          -  Use of other illicit drugs (to include but not limited to benzodiazepines,&#xD;
             amphetamines, cocaine, marijuana)&#xD;
&#xD;
          -  Known liver disease or liver abnormalities as determined by a laboratory test&#xD;
&#xD;
          -  Self-reported history of caffeine use in excess of 400 mg (approximately 8 caffeinated&#xD;
             sodas or 3-4 cups of coffee) per day on average&#xD;
&#xD;
          -  Pregnancy (females)&#xD;
&#xD;
          -  Inability to read and sign consent&#xD;
&#xD;
          -  Use of certain medications (including use of vitamins or supplements), to be&#xD;
             determined on a case-by-case basis by the examining study licensed physician.&#xD;
&#xD;
          -  BMI ≥ 30 (Obese Class I or greater)&#xD;
&#xD;
          -  The PI also maintains the prerogative to disqualify a volunteer if it is deemed that&#xD;
             the volunteer's participation would be unsafe for the volunteer or staff or would be&#xD;
             disruptive to study conduct.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>39 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <verification_date>February 2023</verification_date>
  <study_first_submitted>November 12, 2019</study_first_submitted>
  <study_first_submitted_qc>July 13, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 16, 2020</study_first_posted>
  <last_update_submitted>February 6, 2023</last_update_submitted>
  <last_update_submitted_qc>February 6, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">February 9, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </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/NCT04474015
org study id: WRAIR #1927
nct id: NCT04474015
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Transcranial electrical stimulation (TES) utilizing weak electrical fields (<5 milliamps of
      current - as proposed in the present pilot study) is an extremely safe therapeutic technique
      in use for over 40 years. During that time, TES has never been associated with a serious
      adverse event in a research setting nor a serious reported adverse event in a clinical
      setting. The main side effect associated with TES is irritation of the skin beneath the
      electrodes (as is commonly found from similar preparations used for polysomnography). The
      purpose of this pilot study is to identify the type of electrode preparation that maximizes
      subject comfort during transdermal/transcranial electrical stimulation (TES) using the
      NeuroConn DC Plus Stimulator.
In this study, volunteers will be divided into groups based on the nature of the stimulation
      waveform utilized (DC 0.75 Hz, modified AC 0.75 Hz, AC sinusoidal 3.0 Hz or pulsed
      stimulation of up to 500 ms duration). These waveforms were chosen based on the physiology of
      slow-wave sleep (SWS). Ultimately, the goal is to use TES during sleep to enhance the
      slow-wave activity (SWA) of sleep. Slow-wave sleep is characterized by two main frequency
      bands with differing underlying physiologies: (1) slow oscillation activity with a peak of
      0.75 Hz, and (2) delta activity with a peak of approximately 3.0 Hz. Therefore, in future
      studies, the plan is to stimulate at one or both of these frequencies. The endogenous slow
      activity of the brain consists of electrical fields of "alternating current" with periods of
      relative cellular depolarization and periods of relative cellular hyperpolarization. The goal
      is to enhance this endogenous behavior with transcranial electrical stimulation at the two
      major slow- wave frequencies (0.75 Hz, 3.0 Hz), or using a pulsed stimulation paradigm to
      induce slow wave activity.
allocation: Non-Randomized
intervention model: Sequential Assignment
intervention model description: Groups A, B and C are run sequentially.
primary purpose: Basic Science
masking: None (Open Label)
measure: Sensation scale
time frame: Day 1
description: participants indicate level of sensation on a scale from 1-10; Sensation Scale: 0 to 10 where 10 indicates experiencing severe discomfort; 0 indicates no discomfort
measure: Erythema observation
time frame: Day 1
description: observation of skin erythema following removal of electrodes: At baseline observation for presence of skin lesions/pathology; following stimulation observation of a change or no change in skin lesions/pathology from baseline
arm group label: Part A, Group 1
arm group type: Active Comparator
description: Forearm stimulation during wake (study PART A) - electrode placement = volar surface of forearm, 2 electrodes (cathode and anode): Group 1 will receive forearm stimulation at 0.75 Hz with an oscillating direct current (DC) waveform while awake.
arm group label: Part A, Group 2
arm group type: Active Comparator
description: Forearm stimulation during wake (study PART A) - electrode placement = volar surface of forearm, 2 electrodes (cathode and anode): Group 2 will receive forearm stimulation at 0.75 Hz with a modified alternating current (AC) waveform while awake.
arm group label: Part A, Group 3
arm group type: Active Comparator
description: Forearm stimulation during wake (study PART A) - electrode placement = volar surface of forearm, 2 electrodes (cathode and anode): Group 3 will receive forearm stimulation at 3.0 Hz with an alternating current (AC) sinusoidal waveform while awake.
arm group label: Part B, Group 4
arm group type: Active Comparator
description: Scalp stimulation during sleep (study PART B) - bilateral electrode pairs placed on the upper forehead near the midline (F3 and F4) and adjacent to the ear in the mastoid region (M1 and M2). roup 4 will receive scalp stimulation at 0.75 Hz with an oscillating direct current (DC) waveform during sleep.
arm group label: Part B, Group 5
arm group type: Active Comparator
description: Scalp stimulation during sleep (study PART B) - bilateral electrode pairs placed on the upper forehead near the midline (F3 and F4) and adjacent to the ear in the mastoid region (M1 and M2). Group 5 will receive scalp stimulation at 0.75 Hz with a modified alternating current (AC) waveform during sleep.
arm group label: Part B, Group 6
arm group type: Active Comparator
description: Scalp stimulation during sleep (study PART B) - bilateral electrode pairs placed on the upper forehead near the midline (F3 and F4) and adjacent to the ear in the mastoid region (M1 and M2). Group 6 will receive scalp stimulation at 3.0 Hz with an alternating current (AC) sinusoidal waveform during sleep.
arm group label: Part C, Group 7
arm group type: Active Comparator
description: Pulsed Stimulation: Group 7 (Part C)will receive a series of brief stimulations of up to 500 millisecond duration and of up to 5 milliamperes of current, using either metal electrodes or sponge electrodes as stimulating electrodes.
intervention type: Device
intervention name: transcranial electric stimulation
description: NeuroConn® DC Plus stimulator: the NeuroConn® stimulator can be programmed with specific frequencies of stimulation ranging from 0.5 to 500 Hz. This device is therefore appropriate for the present study to stimulate only at 0.75 or 3.0 Hz. Also, the NeuroConn only allows low current intensities to be chosen. The maximum current intensity that can be delivered with this stimulator is 5 milliamps.
arm group label: Part A, Group 1
arm group label: Part A, Group 2
arm group label: Part A, Group 3
arm group label: Part B, Group 4
arm group label: Part B, Group 5
arm group label: Part B, Group 6
arm group label: Part C, Group 7
criteria: 
gender: All
minimum age: 18 Years
maximum age: 39 Years
healthy volunteers: Accepts Healthy Volunteers
responsible party type: Sponsor
sharing ipd: No