<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/NCT03772717</url>
  </required_header>
  <id_info>
    <org_study_id>IRB00098592</org_study_id>
    <nct_id>NCT03772717</nct_id>
  </id_info>
  <brief_title>Non-invasive Vagus Nerve Stimulation (nVNS) in Pediatric Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)</brief_title>
  <official_title>Non-invasive Vagus Nerve Stimulation (nVNS) in Pediatric Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Emory University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Georgia Institute of Technology</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Emory 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>
  </oversight_info>
  <brief_summary>
    <textblock>
      Participants will be requested to deliver non-invasive vagus nerve stimulation (nVNS) two&#xD;
      times per day, at least five days per week. Participants will be followed for two years with&#xD;
      nVNS as an adjunctive therapy to the standard of care therapy for chronic inflammatory&#xD;
      demyelinating polyneuropathy (CIDP).&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic immune-mediated disease&#xD;
      of the peripheral sensory motor nerves characterized by motor weakness, sensory loss, muscle&#xD;
      wasting and loss of motor ability. The majority of CIDP cases are idiopathic with insidious&#xD;
      onset, relapsing remitting course, and a prolonged clinical course (over years). CIDP&#xD;
      incidence is unknown in pediatric population, however, it is a rare treatable cause of&#xD;
      neuromuscular weakness in children. Treatment of CIDP involves chronic use of steroids,&#xD;
      intravenous immunoglobulin (IVIG) and, rarely, plasma exchange (PLEX). Despite above&#xD;
      mentioned treatments the majority of patients continue to have tremendous disease burden.&#xD;
      There is a need for alternative or adjunctive therapies that can decrease chronic&#xD;
      inflammation effectively and safely in pediatric CIDP patients.&#xD;
&#xD;
      Vagus nerve stimulation has received significant scientific and clinical attention and has&#xD;
      been shown to effectively reduce systemic inflammation. Results from early clinical trials&#xD;
      for treatment of Rheumatoid Arthritis (RA) have demonstrated significant lifestyle benefits&#xD;
      and reduced symptoms in RA patients. Similar benefits of VNS have been observed in Crohn's&#xD;
      disease patients. In these studies, patients are surgically implanted with a stimulator and&#xD;
      electrodes directly on the nerve. Preliminary results have demonstrated safety and efficacy&#xD;
      in patients that previously were unresponsive to traditional pharmacological therapies.&#xD;
      Unfortunately, surgical implantation of a device is difficult and costly.&#xD;
&#xD;
      Recent investigations have significantly increased the understanding of non-invasive vagus&#xD;
      nerve stimulation (nVNS). Compared to traditional implanted vagus nerve stimulation devices,&#xD;
      nVNS uses electrodes placed on the skin surface to stimulate the vagus nerve. nVNS has shown&#xD;
      promise in animal and human models to reduce chronic inflammation in multiple disease states.&#xD;
      By delivering electrical pulses at the skin surface above the vagus nerve, neural pathways&#xD;
      involved in regulating systemic inflammation are activated. Using a handheld device, patients&#xD;
      apply brief durations of stimulation multiple times per day to achieve therapeutic benefit.&#xD;
      nVNS is currently FDA approved for clinical use in the treatment of migraines and cluster&#xD;
      headaches, with on-going clinical studies on epilepsy and systemic inflammation. Preliminary&#xD;
      published results have demonstrated significant therapeutic benefit to the patients with&#xD;
      minimal side-effects such as a feeling of paresthesia at the site of the electrodes which&#xD;
      subsides after turning the stimulation off.&#xD;
&#xD;
      Study participants will administer non-invasive vagus nerve stimulation (nVNS) two times per&#xD;
      day, at least five days per week, as an adjunctive therapy to their standard of care&#xD;
      treatment for CIDP. Participants will be followed for two years to understand the impact of&#xD;
      nVNS on CIDP symptoms and the compliance with nVNS therapies in pediatric patients.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    This study was terminated due to difficulties with enrollment and poor adherence to the study&#xD;
    intervention among participants.&#xD;
  </why_stopped>
  <start_date type="Actual">February 22, 2022</start_date>
  <completion_date type="Actual">June 30, 2022</completion_date>
  <primary_completion_date type="Actual">June 30, 2022</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Nerve Conduction Study - Distal Latency</measure>
    <time_frame>Baseline, Month 12, Month 24</time_frame>
    <description>Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. Latency is the time it takes in milliseconds (ms) for the electrical impulse to travel to the site receiving the stimulation.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Nerve Conduction Study - F Wave Latency</measure>
    <time_frame>Baseline, Month 12, Month 24</time_frame>
    <description>Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. F wave latency is the time it takes in milliseconds (ms) for an electrical signal to travel from the stimulating electrode to the distal muscle and back to the stimulating site. F waves are used to assess polyneuropathy and F wave latency can be extended or even absent in persons with CIDP.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Nerve Conduction Study - Conduction Velocity</measure>
    <time_frame>Baseline, Month 12, Month 24</time_frame>
    <description>Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. Conduction velocity measures the rate of impulse conduction in meters per second (m/s) and is often decreased in patients with CIDP as myelination is affected.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Nerve Conduction Study - Conduction Amplitude</measure>
    <time_frame>Baseline, Month 12, Month 24</time_frame>
    <description>Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. Conduction amplitude is the size of the response to electrical stimulation, measured in millivolts (mV). Reduced amplitude indicates axon loss.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Hand Grip Strength</measure>
    <time_frame>Baseline, Month 6, Month 12, Month 18, Month 24</time_frame>
    <description>Hand grip strength is assessed with a Jamar Handheld Dynamometer for children ages 5-18 years and measures strength in kilograms (kg). Both right and left hand grip strength were measured and the best of three attempts were used for each hand. Increased hand strength is an indicator of effective treatment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Rasch-built Overall Disability Scale (R-ODS) for CIDP Score</measure>
    <time_frame>Baseline, Month 6, Month 12, Month 18, Month 24</time_frame>
    <description>The Rasch-built Overall Disability Scale (R-ODS) used for those with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and gammopathy-related polyneuropathy (MGUSP) is a 24-item scale asking respondents to rate how greatly polyneuropathy impacts activities. Responses are given on a scale of 0 to 2 where 0 indicates it is not possible for the respondent to perform the task and 2 means that the task can be performed without difficulty. Total scores range from 0 to 48 and higher scores indicate greater ability to perform daily and social tasks.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Tumor Necrosis Factor (TNF)-α</measure>
    <time_frame>Baseline, Month 6, Month 12, Month 18, Month 24</time_frame>
    <description>The impact of treatment on serum cytokine profiles will be assessed by measuring TNF-α. Serum cytokine levels will be statistically analyzed on a per patient basis, with each patient's baseline measurements used for comparison. TNF-α is elevated in CIDP patients and a decrease in serum TNF-α is an indication of effective treatment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Interleukin (IL)-1β</measure>
    <time_frame>Baseline, Month 6, Month 12, Month 18, Month 24</time_frame>
    <description>The impact of treatment on serum cytokine profiles will be assessed by measuring IL-1β. Serum cytokine levels will be statistically analyzed on a per patient basis, with each patient's baseline measurements used for comparison. IL-1β is elevated in CIDP patients and a decrease in IL-1β values is an indication of effective treatment.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">2</enrollment>
  <condition>Chronic Inflammatory Demyelinating Polyneuropathy</condition>
  <arm_group>
    <arm_group_label>Non-invasive vagus nerve stimulation (nVNS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants will use the electrical neuromuscular stimulator device, VitalStim 400, which has been used in previous clinical studies for modulation of pain and has received FDA approval. Participants will also continue to take their standard of care medication.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Non-invasive vagus nerve stimulation (nVNS)</intervention_name>
    <description>The nVNS study intervention will be delivered using a handheld electrical neuromuscular stimulator device (VitalStim 400). Participants will deliver nVNS twice per day for 60 minutes each time at least 5 days per week. The two electrodes for the device will be placed on the subjects left cervical (neck) region. Parents will be trained on where to place electrodes, how to ensure that the electrodes make a good contact with the skin, and how to set the stimulation parameters. The stimulation frequency (number of pulses) and amplitude (amount of current) will be set during the initial baseline session in the clinic at a level that prevents discomfort and does not impact cardiorespiratory parameters. The stimulator will be placed in a comfortable position, such as next to the pillow. The stimulators are battery-powered and allow configuration of the stimulation parameters to the comfort of the patient.</description>
    <arm_group_label>Non-invasive vagus nerve stimulation (nVNS)</arm_group_label>
    <other_name>VitalStim 400</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Standard of care treatment</intervention_name>
    <description>Patients will be asked to continue their standard medication regimens which include in most cases will involve 3 weekly infusions of intravenous immunoglobulin (IVIG) (1 gm/kg) and rarely plasma exchange (PLEX).</description>
    <arm_group_label>Non-invasive vagus nerve stimulation (nVNS)</arm_group_label>
    <other_name>intravenous immunoglobulin (IVIG)</other_name>
    <other_name>plasma exchange (PLEX)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion criteria:&#xD;
&#xD;
          -  Diagnosis of CIDP based upon clinical/electrophysiological criteria&#xD;
&#xD;
          -  On treatment for CIDP including IVIG and/ or steroids/plasma exchange&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Inherited polyneuropathy, such as Charcot Tooth Marie disease&#xD;
&#xD;
          -  Abnormal baseline EKG, heart disease, epilepsy, pregnancy, multiple sclerosis and&#xD;
             diabetes mellitus&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>5 Years</minimum_age>
    <maximum_age>21 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Sumit Verma, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Emory University</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Robert Butera, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Georgia Institute of Technology</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Children's Healthcare of Atlanta, Center for Advanced Pediatrics</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30322</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2023</verification_date>
  <study_first_submitted>December 10, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 11, 2018</study_first_posted>
  <results_first_submitted>June 22, 2023</results_first_submitted>
  <results_first_submitted_qc>June 22, 2023</results_first_submitted_qc>
  <results_first_posted type="Actual">July 14, 2023</results_first_posted>
  <last_update_submitted>June 22, 2023</last_update_submitted>
  <last_update_submitted_qc>June 22, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">July 14, 2023</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Emory University</investigator_affiliation>
    <investigator_full_name>Sumit Verma</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <keyword>Pediatrics</keyword>
  <keyword>Vagus nerve stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Polyneuropathies</mesh_term>
    <mesh_term>Polyradiculoneuropathy, Chronic Inflammatory Demyelinating</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Immunoglobulins</mesh_term>
    <mesh_term>Immunoglobulins, Intravenous</mesh_term>
    <mesh_term>gamma-Globulins</mesh_term>
    <mesh_term>Rho(D) Immune Globulin</mesh_term>
  </intervention_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>September 16, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/17/NCT03772717/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <recruitment_details>Participants were recruited from Children's Healthcare of Atlanta in Atlanta, Georgia, USA. Participant enrollment began February 22, 2022 and the study was terminated June 30, 2022, prior to any participant reaching the first follow-up visit at Month 6.</recruitment_details>
      <group_list>
        <group group_id="P1">
          <title>Non-invasive Vagus Nerve Stimulation (nVNS)</title>
          <description>Participants chronic inflammatory demyelinating polyneuropathy (CIDP) used the electrical neuromuscular stimulator device, VitalStim 400, while continuing to take their standard of care medication.&#xD;
Non-invasive vagus nerve stimulation (nVNS): The nVNS study intervention is delivered using a handheld electrical neuromuscular stimulator device (VitalStim 400). Participants are instructed to deliver nVNS twice per day for 60 minutes each time at least 5 days per week. The two electrodes for the device are placed on the subjects left cervical (neck) region. Parents are trained on where to place electrodes, how to ensure that the electrodes make a good contact with the skin, and how to set the stimulation parameters. The stimulation frequency (number of pulses) and amplitude (amount of current) are set during the initial baseline session in the clinic at a level that prevents discomfort and does not impact cardiorespiratory parameters. The stimulator is placed in a comfortable position, such as next to the pillow. The stimulators are battery-powered and allow configuration of the stimulation parameters to the comfort of the patient.&#xD;
Standard of care treatment: Patients are asked to continue their standard medication regimens which include in most cases will involve 3 weekly infusions of intravenous immunoglobulin (IVIG) (1 gm/kg) and rarely plasma exchange (PLEX).</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="2"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Non-invasive Vagus Nerve Stimulation (nVNS)</title>
          <description>Participants with CIDP used the electrical neuromuscular stimulator device, VitalStim 400, while continuing to take their standard of care medication.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="2"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Nerve Conduction Study - Distal Latency</title>
        <description>Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. Latency is the time it takes in milliseconds (ms) for the electrical impulse to travel to the site receiving the stimulation.</description>
        <time_frame>Baseline, Month 12, Month 24</time_frame>
        <population>Participants withdrew from the study prior to completing any follow-up study visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Non-invasive Vagus Nerve Stimulation (nVNS)</title>
            <description>Participants with CIDP used the electrical neuromuscular stimulator device, VitalStim 400, while continuing to take their standard of care medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Nerve Conduction Study - Distal Latency</title>
          <description>Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. Latency is the time it takes in milliseconds (ms) for the electrical impulse to travel to the site receiving the stimulation.</description>
          <population>Participants withdrew from the study prior to completing any follow-up study visits.</population>
          <units>ms</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.8" spread="0.28"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Nerve Conduction Study - F Wave Latency</title>
        <description>Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. F wave latency is the time it takes in milliseconds (ms) for an electrical signal to travel from the stimulating electrode to the distal muscle and back to the stimulating site. F waves are used to assess polyneuropathy and F wave latency can be extended or even absent in persons with CIDP.</description>
        <time_frame>Baseline, Month 12, Month 24</time_frame>
        <population>F wave latency was not performed for one participant at the baseline visit. Participants withdrew from the study prior to completing any follow-up study visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Non-invasive Vagus Nerve Stimulation (nVNS)</title>
            <description>Participants with CIDP used the electrical neuromuscular stimulator device, VitalStim 400, while continuing to take their standard of care medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Nerve Conduction Study - F Wave Latency</title>
          <description>Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. F wave latency is the time it takes in milliseconds (ms) for an electrical signal to travel from the stimulating electrode to the distal muscle and back to the stimulating site. F waves are used to assess polyneuropathy and F wave latency can be extended or even absent in persons with CIDP.</description>
          <population>F wave latency was not performed for one participant at the baseline visit. Participants withdrew from the study prior to completing any follow-up study visits.</population>
          <units>ms</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="20.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Nerve Conduction Study - Conduction Velocity</title>
        <description>Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. Conduction velocity measures the rate of impulse conduction in meters per second (m/s) and is often decreased in patients with CIDP as myelination is affected.</description>
        <time_frame>Baseline, Month 12, Month 24</time_frame>
        <population>Participants withdrew from the study prior to completing any follow-up study visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Non-invasive Vagus Nerve Stimulation (nVNS)</title>
            <description>Participants with CIDP used the electrical neuromuscular stimulator device, VitalStim 400, while continuing to take their standard of care medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Nerve Conduction Study - Conduction Velocity</title>
          <description>Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. Conduction velocity measures the rate of impulse conduction in meters per second (m/s) and is often decreased in patients with CIDP as myelination is affected.</description>
          <population>Participants withdrew from the study prior to completing any follow-up study visits.</population>
          <units>m/s</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="37.5" spread="10.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Nerve Conduction Study - Conduction Amplitude</title>
        <description>Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. Conduction amplitude is the size of the response to electrical stimulation, measured in millivolts (mV). Reduced amplitude indicates axon loss.</description>
        <time_frame>Baseline, Month 12, Month 24</time_frame>
        <population>Participants withdrew from the study prior to completing any follow-up study visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Non-invasive Vagus Nerve Stimulation (nVNS)</title>
            <description>Participants with CIDP used the electrical neuromuscular stimulator device, VitalStim 400, while continuing to take their standard of care medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Nerve Conduction Study - Conduction Amplitude</title>
          <description>Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. Conduction amplitude is the size of the response to electrical stimulation, measured in millivolts (mV). Reduced amplitude indicates axon loss.</description>
          <population>Participants withdrew from the study prior to completing any follow-up study visits.</population>
          <units>mV</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.15" spread="1.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Hand Grip Strength</title>
        <description>Hand grip strength is assessed with a Jamar Handheld Dynamometer for children ages 5-18 years and measures strength in kilograms (kg). Both right and left hand grip strength were measured and the best of three attempts were used for each hand. Increased hand strength is an indicator of effective treatment.</description>
        <time_frame>Baseline, Month 6, Month 12, Month 18, Month 24</time_frame>
        <population>Participants withdrew from the study prior to completing any follow-up study visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Non-invasive Vagus Nerve Stimulation (nVNS)</title>
            <description>Participants with CIDP used the electrical neuromuscular stimulator device, VitalStim 400, while continuing to take their standard of care medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Hand Grip Strength</title>
          <description>Hand grip strength is assessed with a Jamar Handheld Dynamometer for children ages 5-18 years and measures strength in kilograms (kg). Both right and left hand grip strength were measured and the best of three attempts were used for each hand. Increased hand strength is an indicator of effective treatment.</description>
          <population>Participants withdrew from the study prior to completing any follow-up study visits.</population>
          <units>kg</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline - Right Hand</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="19.1" spread="2.97"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline - Left Hand</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18.55" spread="2.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6 - Right Hand</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 6 - Left Hand</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 12 - Right Hand</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 12 - Left Hand</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 18 - Right Hand</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 18 - Left Hand</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 24 - Right Hand</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 24 - Left Hand</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Rasch-built Overall Disability Scale (R-ODS) for CIDP Score</title>
        <description>The Rasch-built Overall Disability Scale (R-ODS) used for those with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and gammopathy-related polyneuropathy (MGUSP) is a 24-item scale asking respondents to rate how greatly polyneuropathy impacts activities. Responses are given on a scale of 0 to 2 where 0 indicates it is not possible for the respondent to perform the task and 2 means that the task can be performed without difficulty. Total scores range from 0 to 48 and higher scores indicate greater ability to perform daily and social tasks.</description>
        <time_frame>Baseline, Month 6, Month 12, Month 18, Month 24</time_frame>
        <population>Participants withdrew from the study prior to completing any follow-up study visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Non-invasive Vagus Nerve Stimulation (nVNS)</title>
            <description>Participants with CIDP used the electrical neuromuscular stimulator device, VitalStim 400, while continuing to take their standard of care medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Rasch-built Overall Disability Scale (R-ODS) for CIDP Score</title>
          <description>The Rasch-built Overall Disability Scale (R-ODS) used for those with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and gammopathy-related polyneuropathy (MGUSP) is a 24-item scale asking respondents to rate how greatly polyneuropathy impacts activities. Responses are given on a scale of 0 to 2 where 0 indicates it is not possible for the respondent to perform the task and 2 means that the task can be performed without difficulty. Total scores range from 0 to 48 and higher scores indicate greater ability to perform daily and social tasks.</description>
          <population>Participants withdrew from the study prior to completing any follow-up study visits.</population>
          <units>score on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="2"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="2"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="45.5" spread="2.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Tumor Necrosis Factor (TNF)-α</title>
        <description>The impact of treatment on serum cytokine profiles will be assessed by measuring TNF-α. Serum cytokine levels will be statistically analyzed on a per patient basis, with each patient's baseline measurements used for comparison. TNF-α is elevated in CIDP patients and a decrease in serum TNF-α is an indication of effective treatment.</description>
        <time_frame>Baseline, Month 6, Month 12, Month 18, Month 24</time_frame>
        <population>One participant had TNF-α value at baseline that was below the limit of detection (&lt;1.7 pg/mL) so the observation for this participant is not included as a summary score cannot be calculated. Participants withdrew from the study prior to completing any follow-up study visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Non-invasive Vagus Nerve Stimulation (nVNS)</title>
            <description>Participants with CIDP used the electrical neuromuscular stimulator device, VitalStim 400, while continuing to take their standard of care medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Tumor Necrosis Factor (TNF)-α</title>
          <description>The impact of treatment on serum cytokine profiles will be assessed by measuring TNF-α. Serum cytokine levels will be statistically analyzed on a per patient basis, with each patient's baseline measurements used for comparison. TNF-α is elevated in CIDP patients and a decrease in serum TNF-α is an indication of effective treatment.</description>
          <population>One participant had TNF-α value at baseline that was below the limit of detection (&lt;1.7 pg/mL) so the observation for this participant is not included as a summary score cannot be calculated. Participants withdrew from the study prior to completing any follow-up study visits.</population>
          <units>picograms per milliliter (pg/mL)</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Interleukin (IL)-1β</title>
        <description>The impact of treatment on serum cytokine profiles will be assessed by measuring IL-1β. Serum cytokine levels will be statistically analyzed on a per patient basis, with each patient's baseline measurements used for comparison. IL-1β is elevated in CIDP patients and a decrease in IL-1β values is an indication of effective treatment.</description>
        <time_frame>Baseline, Month 6, Month 12, Month 18, Month 24</time_frame>
        <population>One participant had a IL-1β value at baseline that was below the limit of detection (&lt;6.5 pg/mL) so the observation for this participant is not included as a summary score cannot be calculated. Participants withdrew from the study prior to completing any follow-up study visits.</population>
        <group_list>
          <group group_id="O1">
            <title>Non-invasive Vagus Nerve Stimulation (nVNS)</title>
            <description>Participants with CIDP used the electrical neuromuscular stimulator device, VitalStim 400, while continuing to take their standard of care medication.</description>
          </group>
        </group_list>
        <measure>
          <title>Interleukin (IL)-1β</title>
          <description>The impact of treatment on serum cytokine profiles will be assessed by measuring IL-1β. Serum cytokine levels will be statistically analyzed on a per patient basis, with each patient's baseline measurements used for comparison. IL-1β is elevated in CIDP patients and a decrease in IL-1β values is an indication of effective treatment.</description>
          <population>One participant had a IL-1β value at baseline that was below the limit of detection (&lt;6.5 pg/mL) so the observation for this participant is not included as a summary score cannot be calculated. Participants withdrew from the study prior to completing any follow-up study visits.</population>
          <units>pg/mL</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="1"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="1"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Month 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 12</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 18</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
            <class>
              <title>Month 24</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="0"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Information on adverse events was collected from the time individuals gave consent to participate in the study until the participant withdrew from the study (up to 3 months).</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Non-invasive Vagus Nerve Stimulation (nVNS)</title>
          <description>Participants with CIDP used the electrical neuromuscular stimulator device, VitalStim 400, while continuing to take their standard of care medication.</description>
        </group>
      </group_list>
      <serious_events>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Tingling, numbness, and pain in limbs</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="2"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Sumit Verma, MD</name_or_title>
      <organization>Emory University</organization>
      <phone>404-785-9893</phone>
      <email>sumit.verma@emory.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT03772717
org study id: IRB00098592
nct id: NCT03772717
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
Participants will be requested to deliver non-invasive vagus nerve stimulation (nVNS) two
      times per day, at least five days per week. Participants will be followed for two years with
      nVNS as an adjunctive therapy to the standard of care therapy for chronic inflammatory
      demyelinating polyneuropathy (CIDP).
Chronic inflammatory demyelinating polyneuropathy (CIDP) is a chronic immune-mediated disease
      of the peripheral sensory motor nerves characterized by motor weakness, sensory loss, muscle
      wasting and loss of motor ability. The majority of CIDP cases are idiopathic with insidious
      onset, relapsing remitting course, and a prolonged clinical course (over years). CIDP
      incidence is unknown in pediatric population, however, it is a rare treatable cause of
      neuromuscular weakness in children. Treatment of CIDP involves chronic use of steroids,
      intravenous immunoglobulin (IVIG) and, rarely, plasma exchange (PLEX). Despite above
      mentioned treatments the majority of patients continue to have tremendous disease burden.
      There is a need for alternative or adjunctive therapies that can decrease chronic
      inflammation effectively and safely in pediatric CIDP patients.

      Vagus nerve stimulation has received significant scientific and clinical attention and has
      been shown to effectively reduce systemic inflammation. Results from early clinical trials
      for treatment of Rheumatoid Arthritis (RA) have demonstrated significant lifestyle benefits
      and reduced symptoms in RA patients. Similar benefits of VNS have been observed in Crohn's
      disease patients. In these studies, patients are surgically implanted with a stimulator and
      electrodes directly on the nerve. Preliminary results have demonstrated safety and efficacy
      in patients that previously were unresponsive to traditional pharmacological therapies.
      Unfortunately, surgical implantation of a device is difficult and costly.

      Recent investigations have significantly increased the understanding of non-invasive vagus
      nerve stimulation (nVNS). Compared to traditional implanted vagus nerve stimulation devices,
      nVNS uses electrodes placed on the skin surface to stimulate the vagus nerve. nVNS has shown
      promise in animal and human models to reduce chronic inflammation in multiple disease states.
      By delivering electrical pulses at the skin surface above the vagus nerve, neural pathways
      involved in regulating systemic inflammation are activated. Using a handheld device, patients
      apply brief durations of stimulation multiple times per day to achieve therapeutic benefit.
      nVNS is currently FDA approved for clinical use in the treatment of migraines and cluster
      headaches, with on-going clinical studies on epilepsy and systemic inflammation. Preliminary
      published results have demonstrated significant therapeutic benefit to the patients with
      minimal side-effects such as a feeling of paresthesia at the site of the electrodes which
      subsides after turning the stimulation off.

      Study participants will administer non-invasive vagus nerve stimulation (nVNS) two times per
      day, at least five days per week, as an adjunctive therapy to their standard of care
      treatment for CIDP. Participants will be followed for two years to understand the impact of
      nVNS on CIDP symptoms and the compliance with nVNS therapies in pediatric patients.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Nerve Conduction Study - Distal Latency
time frame: Baseline, Month 12, Month 24
description: Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. Latency is the time it takes in milliseconds (ms) for the electrical impulse to travel to the site receiving the stimulation.
measure: Nerve Conduction Study - F Wave Latency
time frame: Baseline, Month 12, Month 24
description: Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. F wave latency is the time it takes in milliseconds (ms) for an electrical signal to travel from the stimulating electrode to the distal muscle and back to the stimulating site. F waves are used to assess polyneuropathy and F wave latency can be extended or even absent in persons with CIDP.
measure: Nerve Conduction Study - Conduction Velocity
time frame: Baseline, Month 12, Month 24
description: Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. Conduction velocity measures the rate of impulse conduction in meters per second (m/s) and is often decreased in patients with CIDP as myelination is affected.
measure: Nerve Conduction Study - Conduction Amplitude
time frame: Baseline, Month 12, Month 24
description: Motor nerve conduction studies are used to examine conduction of electrical impulses along nerves. Electrodes are placed on the skin in specific areas to evaluate peripheral nerves. An electrode stimulates a nerve while the receiving site records how well electrical impulses are being conducted along the nerve. Conduction amplitude is the size of the response to electrical stimulation, measured in millivolts (mV). Reduced amplitude indicates axon loss.
measure: Hand Grip Strength
time frame: Baseline, Month 6, Month 12, Month 18, Month 24
description: Hand grip strength is assessed with a Jamar Handheld Dynamometer for children ages 5-18 years and measures strength in kilograms (kg). Both right and left hand grip strength were measured and the best of three attempts were used for each hand. Increased hand strength is an indicator of effective treatment.
measure: Rasch-built Overall Disability Scale (R-ODS) for CIDP Score
time frame: Baseline, Month 6, Month 12, Month 18, Month 24
description: The Rasch-built Overall Disability Scale (R-ODS) used for those with Guillain-Barré syndrome (GBS), chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), and gammopathy-related polyneuropathy (MGUSP) is a 24-item scale asking respondents to rate how greatly polyneuropathy impacts activities. Responses are given on a scale of 0 to 2 where 0 indicates it is not possible for the respondent to perform the task and 2 means that the task can be performed without difficulty. Total scores range from 0 to 48 and higher scores indicate greater ability to perform daily and social tasks.
measure: Tumor Necrosis Factor (TNF)-α
time frame: Baseline, Month 6, Month 12, Month 18, Month 24
description: The impact of treatment on serum cytokine profiles will be assessed by measuring TNF-α. Serum cytokine levels will be statistically analyzed on a per patient basis, with each patient's baseline measurements used for comparison. TNF-α is elevated in CIDP patients and a decrease in serum TNF-α is an indication of effective treatment.
measure: Interleukin (IL)-1β
time frame: Baseline, Month 6, Month 12, Month 18, Month 24
description: The impact of treatment on serum cytokine profiles will be assessed by measuring IL-1β. Serum cytokine levels will be statistically analyzed on a per patient basis, with each patient's baseline measurements used for comparison. IL-1β is elevated in CIDP patients and a decrease in IL-1β values is an indication of effective treatment.
arm group label: Non-invasive vagus nerve stimulation (nVNS)
arm group type: Experimental
description: Participants will use the electrical neuromuscular stimulator device, VitalStim 400, which has been used in previous clinical studies for modulation of pain and has received FDA approval. Participants will also continue to take their standard of care medication.
intervention type: Device
intervention name: Non-invasive vagus nerve stimulation (nVNS)
description: The nVNS study intervention will be delivered using a handheld electrical neuromuscular stimulator device (VitalStim 400). Participants will deliver nVNS twice per day for 60 minutes each time at least 5 days per week. The two electrodes for the device will be placed on the subjects left cervical (neck) region. Parents will be trained on where to place electrodes, how to ensure that the electrodes make a good contact with the skin, and how to set the stimulation parameters. The stimulation frequency (number of pulses) and amplitude (amount of current) will be set during the initial baseline session in the clinic at a level that prevents discomfort and does not impact cardiorespiratory parameters. The stimulator will be placed in a comfortable position, such as next to the pillow. The stimulators are battery-powered and allow configuration of the stimulation parameters to the comfort of the patient.
arm group label: Non-invasive vagus nerve stimulation (nVNS)
other name: VitalStim 400
intervention type: Other
intervention name: Standard of care treatment
description: Patients will be asked to continue their standard medication regimens which include in most cases will involve 3 weekly infusions of intravenous immunoglobulin (IVIG) (1 gm/kg) and rarely plasma exchange (PLEX).
arm group label: Non-invasive vagus nerve stimulation (nVNS)
other name: intravenous immunoglobulin (IVIG)
other name: plasma exchange (PLEX)
criteria: 
gender: All
minimum age: 5 Years
maximum age: 21 Years
healthy volunteers: No
last name: Sumit Verma, MD
role: Principal Investigator
affiliation: Emory University
last name: Robert Butera, PhD
role: Principal Investigator
affiliation: Georgia Institute of Technology
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Emory University
investigator full name: Sumit Verma
investigator title: Associate Professor
mesh term: Polyneuropathies
mesh term: Polyradiculoneuropathy, Chronic Inflammatory Demyelinating
mesh term: Immunoglobulins
mesh term: Immunoglobulins, Intravenous
mesh term: gamma-Globulins
mesh term: Rho(D) Immune Globulin
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 