<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/NCT03292159</url>
  </required_header>
  <id_info>
    <org_study_id>2017P000129</org_study_id>
    <nct_id>NCT03292159</nct_id>
  </id_info>
  <brief_title>Transcutaneous Vagus Nerve Stimulation for Motor Recovery After Stroke</brief_title>
  <official_title>Safety and Effectiveness of Transcutaneous Vagus Nerve Stimulation Therapy to Improve Motor Recovery After Stroke</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Massachusetts General Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Dana Foundation, Spaulding Rehabilitation Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Massachusetts General Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study will evaluate the safety and effectiveness of Respiratory-gated Auricular Vagal&#xD;
      Afferent Nerve Stimulation (RAVANS) for improving motor recovery after stroke. Subacute&#xD;
      stroke patients will receive RAVANS or sham stimulation concurrent with arm motor training&#xD;
      during 10 intervention sessions occurring daily for 30 minutes over 2 weeks. The safety and&#xD;
      improvements in arm motor function after the intervention will be compared in patients&#xD;
      receiving RAVANS to those receiving sham stimulation.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will evaluate the safety, feasibility and effectiveness of Respiratory-gated&#xD;
      Auricular Vagal Afferent Nerve Stimulation (RAVANS) for improving motor recovery after&#xD;
      stroke. Subacute stroke patients will be randomized to RAVANS or sham stimulation groups.&#xD;
      Patients will receive RAVANS or sham stimulation concurrent with arm motor training during 10&#xD;
      sessions occurring daily for 30 minutes over 2 weeks. Safety will be compared in patients&#xD;
      receiving RAVANS to those receiving sham stimulation. Feasibility will be evaluated by&#xD;
      recruitment into the study and retention of enrolled patients. Changes in arm motor function&#xD;
      will be compared between RAVANS and sham stimulation groups from baseline to immediately&#xD;
      after the intervention period and to function at 3-months after stroke.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    funding not continued&#xD;
  </why_stopped>
  <start_date type="Actual">May 17, 2018</start_date>
  <completion_date type="Actual">November 20, 2018</completion_date>
  <primary_completion_date type="Actual">November 20, 2018</primary_completion_date>
  <phase>Phase 1/Phase 2</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Upper extremity motor impairment</measure>
    <time_frame>Baseline to just after 10 intervention sessions, and baseline to 3 months post-stroke</time_frame>
    <description>Change in upper extremity subtest of Fugl Meyer Assessment (FMA-UE) score</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Upper extremity motor function</measure>
    <time_frame>Baseline to just after 10 intervention sessions, and baseline to 3 months post-stroke</time_frame>
    <description>Change in Action Research Arm Test (ARAT) score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Grip force control</measure>
    <time_frame>Baseline to just after 10 intervention sessions, and baseline to 3 months post-stroke</time_frame>
    <description>Change in accuracy, variability and temporal structure of performance on a grip force control task</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Upper extremity disability</measure>
    <time_frame>Baseline to 3 months post-stroke</time_frame>
    <description>Change in hand subtest of Stroke Impact Scale (SIS-hand) score</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mood state, anxiety and depression</measure>
    <time_frame>Baseline to 3 months post-stroke</time_frame>
    <description>Change in Hospital Anxiety and Depression Scale (HADS) scores</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Stroke</condition>
  <condition>Upper Extremity Paresis</condition>
  <arm_group>
    <arm_group_label>RAVANS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham stimulation</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Active RAVANS concurrent with arm motor training</intervention_name>
    <description>Patient receives non-painful, sensory-level stimulation to the skin of left outer ear, where nerve endings of the auricular branch of the vagus nerve reside, while participating in arm motor training</description>
    <arm_group_label>RAVANS</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Inactive RAVANS concurrent with arm motor training</intervention_name>
    <description>Patient does not receive stimulation delivered to the skin of left outer ear while participating in arm motor training</description>
    <arm_group_label>Sham stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Supratentorial ischemic or hemorrhagic stroke incurred 4-30 days prior;&#xD;
&#xD;
          -  Contralesional UL motor impairment defined by NIHSS item 5 score 1 or 2 (scale 0-4);&#xD;
&#xD;
          -  Age ≥ 18;&#xD;
&#xD;
          -  Able to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Implanted electronic device (e.g., pacemaker, neurostimulator);&#xD;
&#xD;
          -  Pregnancy;&#xD;
&#xD;
          -  Major psychiatric or medical condition that could interfere with study participation;&#xD;
&#xD;
          -  Medical condition affecting left ear that could interfere with delivering RAVANS&#xD;
             (e.g., wound, infection, malignancy, hypoesthesia);&#xD;
&#xD;
          -  Significant pre-existing disability of stroke-affected UL in activities of daily&#xD;
             living due to prior stroke or other medical cause defined by Stroke Impact Scale item&#xD;
             7 (SIS-hand) mean score &lt; 4 (scale: 0-5);&#xD;
&#xD;
          -  History of seizure during year before stroke or &gt; 1 post-stroke seizure;&#xD;
&#xD;
          -  Significant cognitive or language impairment that would interfere with informed&#xD;
             consent or study participation;&#xD;
&#xD;
          -  Severe dysphagia;&#xD;
&#xD;
          -  Bradycardia defined as resting heart rate &lt; 50 bpm;&#xD;
&#xD;
          -  Nonsustained ventricular tachycardia;&#xD;
&#xD;
          -  Cardiac conduction disorder (i.e., bundle branch block, heart block, long Q-T&#xD;
             syndrome);&#xD;
&#xD;
          -  History of asystole;&#xD;
&#xD;
          -  History of recurrent vaso-vagal syncope;&#xD;
&#xD;
          -  Hypotension defined as blood pressure &lt; 90/60 mmHg.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Spaulding Rehabilitation Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02129</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>September 2021</verification_date>
  <study_first_submitted>September 20, 2017</study_first_submitted>
  <study_first_submitted_qc>September 22, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 25, 2017</study_first_posted>
  <last_update_submitted>September 14, 2021</last_update_submitted>
  <last_update_submitted_qc>September 14, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">September 21, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Massachusetts General Hospital</investigator_affiliation>
    <investigator_full_name>Judith Schaechter</investigator_full_name>
    <investigator_title>Assistant Professor, Department of Radiology, Harvard Medical School</investigator_title>
  </responsible_party>
  <keyword>stroke</keyword>
  <keyword>vagus nerve stimulation</keyword>
  <keyword>upper extremity paresis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscle Weakness</mesh_term>
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Paresis</mesh_term>
  </condition_browse>
  <!-- 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/NCT03292159
org study id: 2017P000129
nct id: NCT03292159
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: No
is us export: No
This study will evaluate the safety and effectiveness of Respiratory-gated Auricular Vagal
      Afferent Nerve Stimulation (RAVANS) for improving motor recovery after stroke. Subacute
      stroke patients will receive RAVANS or sham stimulation concurrent with arm motor training
      during 10 intervention sessions occurring daily for 30 minutes over 2 weeks. The safety and
      improvements in arm motor function after the intervention will be compared in patients
      receiving RAVANS to those receiving sham stimulation.
This study will evaluate the safety, feasibility and effectiveness of Respiratory-gated
      Auricular Vagal Afferent Nerve Stimulation (RAVANS) for improving motor recovery after
      stroke. Subacute stroke patients will be randomized to RAVANS or sham stimulation groups.
      Patients will receive RAVANS or sham stimulation concurrent with arm motor training during 10
      sessions occurring daily for 30 minutes over 2 weeks. Safety will be compared in patients
      receiving RAVANS to those receiving sham stimulation. Feasibility will be evaluated by
      recruitment into the study and retention of enrolled patients. Changes in arm motor function
      will be compared between RAVANS and sham stimulation groups from baseline to immediately
      after the intervention period and to function at 3-months after stroke.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Upper extremity motor impairment
time frame: Baseline to just after 10 intervention sessions, and baseline to 3 months post-stroke
description: Change in upper extremity subtest of Fugl Meyer Assessment (FMA-UE) score
measure: Upper extremity motor function
time frame: Baseline to just after 10 intervention sessions, and baseline to 3 months post-stroke
description: Change in Action Research Arm Test (ARAT) score
measure: Grip force control
time frame: Baseline to just after 10 intervention sessions, and baseline to 3 months post-stroke
description: Change in accuracy, variability and temporal structure of performance on a grip force control task
measure: Upper extremity disability
time frame: Baseline to 3 months post-stroke
description: Change in hand subtest of Stroke Impact Scale (SIS-hand) score
measure: Mood state, anxiety and depression
time frame: Baseline to 3 months post-stroke
description: Change in Hospital Anxiety and Depression Scale (HADS) scores
arm group label: RAVANS
arm group type: Experimental
arm group label: Sham stimulation
arm group type: Sham Comparator
intervention type: Device
intervention name: Active RAVANS concurrent with arm motor training
description: Patient receives non-painful, sensory-level stimulation to the skin of left outer ear, where nerve endings of the auricular branch of the vagus nerve reside, while participating in arm motor training
arm group label: RAVANS
intervention type: Device
intervention name: Inactive RAVANS concurrent with arm motor training
description: Patient does not receive stimulation delivered to the skin of left outer ear while participating in arm motor training
arm group label: Sham stimulation
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Massachusetts General Hospital
investigator full name: Judith Schaechter
investigator title: Assistant Professor, Department of Radiology, Harvard Medical School
mesh term: Muscle Weakness
mesh term: Stroke
mesh term: Paresis