<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/NCT03827941</url>
  </required_header>
  <id_info>
    <org_study_id>2017P000894</org_study_id>
    <nct_id>NCT03827941</nct_id>
  </id_info>
  <brief_title>Auricular Transcutaneous Electrical Nerve Stimulation Treatment of Autism</brief_title>
  <official_title>Auricular Transcutaneous Electrical Nerve Stimulation Treatment of Autism</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      In this study, investigators will examine the treatment effects of transcutaneous electrical&#xD;
      nerve stimulation with different stimulation frequencies on individuals with autism.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      In this study, investigators will examine the treatment effect of transcutaneous electrical&#xD;
      nerve stimulation at auricular area with vagus nerve distribution on high-functioning&#xD;
      individuals with autism. Specifically, investigators will choose two ear acupoints: heart and&#xD;
      shenmen. Participants will be randomized to either 1 Hz or 20 Hz tVNS group (up to 5 times&#xD;
      per week) for three weeks.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Not yet recruiting</overall_status>
  <start_date type="Anticipated">October 1, 2022</start_date>
  <completion_date type="Anticipated">January 28, 2024</completion_date>
  <primary_completion_date type="Anticipated">January 28, 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>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Autism Treatment Evaluation Checklist (ATEC)</measure>
    <time_frame>Baseline and after 3-week treatment</time_frame>
    <description>ATEC will be reported by investigator in a total and for each of the 4 subscales as follows: (1) speech/language/communication subscale; (2) social subscale; (3) sensory and cognitive awareness subscale; and (4) health / physical / behavior problem subscale. The total score ranges from 0 to 179; a higher score indicated worsening while a lower score indicated improvement.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Aberrant Behavior Checklist (ABC)</measure>
    <time_frame>Baseline and after 3-week treatment</time_frame>
    <description>The factors of the ABC have been labeled as follows: (I) Irritability, Agitation, Crying; (II) Lethargy, Social Withdrawal; (III) Stereotypic Behavior; (IV) Hyperactivity, Noncompliance; and (V) Inappropriate Speech.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Clinical Global Impression-Improvement (CGI-I)</measure>
    <time_frame>Baseline and after 3-week treatment</time_frame>
    <description>Overall improvement in autism will be assessed using the Clinical Global Impression-Improvement (CGI-I) scale, a 7-point scale from 1 = very much improved to 7 = very much worse.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in PROMIS Sleep Disturbance Short Form</measure>
    <time_frame>Baseline and after 3-week treatment</time_frame>
    <description>This questionnaire is used to assess the pure domain of sleep disturbance in adults.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Penn State Worry Questionnaire</measure>
    <time_frame>Baseline and after 3-week treatment</time_frame>
    <description>This is the standard assessment of worry and consists of 16 questions rated from 1 to 5 from &quot;Not typical of me&quot; to &quot;Very typical of me&quot;.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Sleep Quality Assessment (PSQI)</measure>
    <time_frame>Baseline and after 3-week treatment</time_frame>
    <description>The Pittsburgh Sleep Quality Index (PSQI) is an effective instrument used to measure the quality and patterns of sleep in adults. It differentiates &quot;poor&quot; from &quot;good&quot; sleep quality by measuring seven areas (components): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction over the last week.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>PROMIS-29</measure>
    <time_frame>Baseline and after 3-week treatment</time_frame>
    <description>The PROMIS-29 assesses pain intensity, physical function, depression, anxiety, fatigue, sleep disturbance, interference, and social role and activity in the past 7 days</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>EEG (optional)</measure>
    <time_frame>Baseline and after 3-week treatment</time_frame>
    <description>Resting state EEG (filter 1-50 Hz) will be collected</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Salivary oxytocin quantification (optional)</measure>
    <time_frame>Baseline and after 3-week treatment</time_frame>
    <description>A total of 4-mL of unstimulated saliva will be collected</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quantification of species-level L. reuteri abundance in human stool samples (optional)</measure>
    <time_frame>Baseline and after 3-week treatment</time_frame>
    <description>Stool samples will be collected at home following our provided instructions.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Autonomic measurements via wristband photoplethysmograph (PPG) sensor (optional)</measure>
    <time_frame>Baseline and after 3-week treatment</time_frame>
    <description>6 minutes PPG data will be collected</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>ECG (optional)</measure>
    <time_frame>Baseline and after 3-week treatment</time_frame>
    <description>6 minutes raw ECG data will be collected for Heart rate variability (HRV) analysis</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Pulse oximetry measurements (optional)</measure>
    <time_frame>Baseline and after 3-week treatment</time_frame>
    <description>SpCO will be measured at different time points</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">40</enrollment>
  <condition>Autism Spectrum Disorder</condition>
  <arm_group>
    <arm_group_label>1 Hz group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>1 Hz Auricular transcutaneous electrical nerve stimulation High-functioning individuals with autism randomized to this group will receive 1 Hz tVNS stimulation for 30 minutes/day up to 5 times/week for 3 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>20 Hz group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>20 Hz Auricular transcutaneous electrical nerve stimulation High-functioning individuals with autism randomized to this group will receive 20 Hz tVNS stimulation for 30 minutes/day up to 5 times/week for 3 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>1 Hz Auricular transcutaneous electrical nerve stimulation</intervention_name>
    <description>High-functioning individuals with autism randomized to this group will receive 1 Hz tVNS stimulation for 30 minutes/day up to 5 times/week for 3 weeks.</description>
    <arm_group_label>1 Hz group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>20 Hz Auricular transcutaneous electrical nerve stimulation</intervention_name>
    <description>High-functioning individuals with autism randomized to this group will receive 1 Hz tVNS stimulation for 30 minutes/day up to 5 times/week for 3 weeks.</description>
    <arm_group_label>20 Hz group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Autism diagnosed based on DSM-V classification criteria&#xD;
&#xD;
          2. 18-60 year old high functioning adult autism patients (e.g. Asperger's, IQ equal or&#xD;
             greater than 80)&#xD;
&#xD;
          3. Subjects who do not show aggressive behaviors based on neuro/psychiatric evaluations&#xD;
             as determined by a licensed study physician.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. A history of chronic serious infection, any current infection, any type of cancer or&#xD;
             autoimmune disease or other severe diseases;&#xD;
&#xD;
          2. Subjects taking any medications that confound the study results&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jian Kong</last_name>
    <role>Principal Investigator</role>
    <affiliation>MGH</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Amy Ursitti</last_name>
    <phone>6177267893</phone>
    <email>aursitti@mgh.harvard.edu</email>
  </overall_contact>
  <verification_date>September 2022</verification_date>
  <study_first_submitted>January 28, 2019</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>September 6, 2022</last_update_submitted>
  <last_update_submitted_qc>September 6, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">September 9, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Jian Kong</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Autistic Disorder</mesh_term>
    <mesh_term>Autism Spectrum Disorder</mesh_term>
  </condition_browse>
  <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/NCT03827941
org study id: 2017P000894
nct id: NCT03827941
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
In this study, investigators will examine the treatment effects of transcutaneous electrical
      nerve stimulation with different stimulation frequencies on individuals with autism.
In this study, investigators will examine the treatment effect of transcutaneous electrical
      nerve stimulation at auricular area with vagus nerve distribution on high-functioning
      individuals with autism. Specifically, investigators will choose two ear acupoints: heart and
      shenmen. Participants will be randomized to either 1 Hz or 20 Hz tVNS group (up to 5 times
      per week) for three weeks.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Change in Autism Treatment Evaluation Checklist (ATEC)
time frame: Baseline and after 3-week treatment
description: ATEC will be reported by investigator in a total and for each of the 4 subscales as follows: (1) speech/language/communication subscale; (2) social subscale; (3) sensory and cognitive awareness subscale; and (4) health / physical / behavior problem subscale. The total score ranges from 0 to 179; a higher score indicated worsening while a lower score indicated improvement.
measure: Change in Aberrant Behavior Checklist (ABC)
time frame: Baseline and after 3-week treatment
description: The factors of the ABC have been labeled as follows: (I) Irritability, Agitation, Crying; (II) Lethargy, Social Withdrawal; (III) Stereotypic Behavior; (IV) Hyperactivity, Noncompliance; and (V) Inappropriate Speech.
measure: Change in Clinical Global Impression-Improvement (CGI-I)
time frame: Baseline and after 3-week treatment
description: Overall improvement in autism will be assessed using the Clinical Global Impression-Improvement (CGI-I) scale, a 7-point scale from 1 = very much improved to 7 = very much worse.
measure: Change in PROMIS Sleep Disturbance Short Form
time frame: Baseline and after 3-week treatment
description: This questionnaire is used to assess the pure domain of sleep disturbance in adults.
measure: Change in Penn State Worry Questionnaire
time frame: Baseline and after 3-week treatment
description: This is the standard assessment of worry and consists of 16 questions rated from 1 to 5 from "Not typical of me" to "Very typical of me".
measure: Change in Sleep Quality Assessment (PSQI)
time frame: Baseline and after 3-week treatment
description: The Pittsburgh Sleep Quality Index (PSQI) is an effective instrument used to measure the quality and patterns of sleep in adults. It differentiates "poor" from "good" sleep quality by measuring seven areas (components): subjective sleep quality, sleep latency, sleep duration, habitual sleep efficiency, sleep disturbances, use of sleeping medications, and daytime dysfunction over the last week.
measure: PROMIS-29
time frame: Baseline and after 3-week treatment
description: The PROMIS-29 assesses pain intensity, physical function, depression, anxiety, fatigue, sleep disturbance, interference, and social role and activity in the past 7 days
measure: EEG (optional)
time frame: Baseline and after 3-week treatment
description: Resting state EEG (filter 1-50 Hz) will be collected
measure: Salivary oxytocin quantification (optional)
time frame: Baseline and after 3-week treatment
description: A total of 4-mL of unstimulated saliva will be collected
measure: Quantification of species-level L. reuteri abundance in human stool samples (optional)
time frame: Baseline and after 3-week treatment
description: Stool samples will be collected at home following our provided instructions.
measure: Autonomic measurements via wristband photoplethysmograph (PPG) sensor (optional)
time frame: Baseline and after 3-week treatment
description: 6 minutes PPG data will be collected
measure: ECG (optional)
time frame: Baseline and after 3-week treatment
description: 6 minutes raw ECG data will be collected for Heart rate variability (HRV) analysis
measure: Pulse oximetry measurements (optional)
time frame: Baseline and after 3-week treatment
description: SpCO will be measured at different time points
arm group label: 1 Hz group
arm group type: Active Comparator
description: 1 Hz Auricular transcutaneous electrical nerve stimulation High-functioning individuals with autism randomized to this group will receive 1 Hz tVNS stimulation for 30 minutes/day up to 5 times/week for 3 weeks.
arm group label: 20 Hz group
arm group type: Active Comparator
description: 20 Hz Auricular transcutaneous electrical nerve stimulation High-functioning individuals with autism randomized to this group will receive 20 Hz tVNS stimulation for 30 minutes/day up to 5 times/week for 3 weeks.
intervention type: Other
intervention name: 1 Hz Auricular transcutaneous electrical nerve stimulation
description: High-functioning individuals with autism randomized to this group will receive 1 Hz tVNS stimulation for 30 minutes/day up to 5 times/week for 3 weeks.
arm group label: 1 Hz group
intervention type: Other
intervention name: 20 Hz Auricular transcutaneous electrical nerve stimulation
description: High-functioning individuals with autism randomized to this group will receive 1 Hz tVNS stimulation for 30 minutes/day up to 5 times/week for 3 weeks.
arm group label: 20 Hz group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 60 Years
healthy volunteers: No
last name: Jian Kong
role: Principal Investigator
affiliation: MGH
last name: Amy Ursitti
phone: 6177267893
email: aursitti@mgh.harvard.edu
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Jian Kong
investigator title: Associate Professor
mesh term: Autistic Disorder
mesh term: Autism Spectrum Disorder
sharing ipd: No