<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/NCT02252666</url>
  </required_header>
  <id_info>
    <org_study_id>2013-1060</org_study_id>
    <nct_id>NCT02252666</nct_id>
  </id_info>
  <brief_title>Exploring the Use of Non-invasive Neuromodulation Combined With Exercise in People With Advanced Multiple Sclerosis (MS)</brief_title>
  <official_title>Exploring the Use of Non-invasive Neuromodulation Combined With Exercise in People With Advanced Multiple Sclerosis (MS)</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Wisconsin, Madison</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>
    <is_unapproved_device>Yes</is_unapproved_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      The investigators hypothesis is that electrical stimulation to the tongue that directly&#xD;
      stimulates two cranial nerve nuclei (Trigeminal and Facial Nerve Nuclei), will excite neural&#xD;
      impulses to the brainstem and cerebellum. The investigators call this cranial nerve&#xD;
      non-invasive neuromodulation (CN-NINM). The activation of these structures induces&#xD;
      neuroplasticity when combined with specific physical exercises, can reduce symptoms of&#xD;
      advanced MS, targeting primarily postural stability (sitting and standing), upper extremity&#xD;
      movement, and ability to perform self-transfers.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The intervention will be similar to that used in the investigators previous work with&#xD;
      movement disorders, and will be tailored to the address issues unique to individuals with&#xD;
      advanced MS.&#xD;
&#xD;
      The study will enroll a total of 6 subjects having advanced MS that present with significant&#xD;
      seated and standing balance, posture, or movement control deficits due to MS.&#xD;
&#xD;
      Subjects will complete twice-daily lab training for two weeks (5 days/week). Each lab&#xD;
      training (morning and afternoon) includes 1.5 to 2 hours of instruction in balance, posture&#xD;
      and gait activities; therapeutic exercise for isolated muscle control; transfer training; and&#xD;
      relaxation training.&#xD;
&#xD;
      Activities are performed in 20-minute sessions with concomitant electrical stimulation of the&#xD;
      tongue. The intervention is customized according to each subject's particular symptoms and&#xD;
      tolerance. If a subject is not able to perform this amount of training, the training will be&#xD;
      adapted to a level that is tolerable.&#xD;
&#xD;
      After these 2 weeks, subjects will continue to perform these same intervention activities at&#xD;
      home for 4 weeks. They will return to the lab for 1 week of training and testing, then&#xD;
      perform home training for 4 weeks. This cycle is repeated for a total of 5 cycles.&#xD;
&#xD;
      After the 6 months have been completed, subjects may choose to participate in an optional&#xD;
      second phase of the study. The second phase includes an additional 12 months of participation&#xD;
      in which subjects perform the intervention activities at home training and return to the lab&#xD;
      on time per month for 2 hours of testing and 2 hours of training.&#xD;
&#xD;
      If successful, this study would indicate that CN-NINM intervention may reduce the symptoms of&#xD;
      advanced MS.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>March 2014</start_date>
  <completion_date type="Actual">June 28, 2017</completion_date>
  <primary_completion_date type="Actual">January 2017</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>Trunk Impairment Scale (TIS)</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, and 21 weeks</time_frame>
    <description>Static and dynamic sitting balance and trunk coordination are evaluated by a clinician. It is scored on a scale from 0-23, where the higher the score, the more improved the balance. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Static Standing Balance Test</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
    <description>Clinician measures standing balance for up to 30 seconds in each of 5 conditions: feet 10 cm apart, feet together, stride stance, tandem stance, and single leg stance with eyes open and eyes closed. Total score is the sum of all 5 conditions. Higher scores indicate better balance. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Impact of Visual Impairment Scale (IVIS)</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, and 21 weeks</time_frame>
    <description>A 5-item self-report questionnaire that assesses the extent to which various activities dependent upon vision are affected by MS-related visual problems. Scores range from 0-15, with higher scores indicating a greater impact of visual problems on daily activities. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Medical Outcomes Study (MOS) Pain Effects Scale (PES)</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, and 21 weeks</time_frame>
    <description>A self-report scale that assesses the ways in which pain and unpleasant sensation interfere with mood, ability to walk or move, sleep, work, recreation, and enjoyment of life. This assessment is used for subjects who have pain. Scores can range from 6-30. Items are scaled so that higher scores indicate a greater impact of pain on a patient's mood and behavior. Symptom specific test, only used for participants who presented symptom. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bladder Control Scale (BLCS)</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
    <description>A 4-item self-report scale to evaluate the impact of bladder control on lifestyle. This assessment is used for subjects with bladder issues. Scores can range from 0-22, with higher scores indicating greater bladder control problems. Symptom specific test, only used for participants who presented symptom. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Bowel Control Scale (BWCS)</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
    <description>A 5-item self-report scale to evaluate the impact of bowel control on lifestyle. This assessment is used for subjects with bowel issues. Scores can range from 0-26, with higher scores indicating greater bowel control problems. Symptom specific test, only used for participants who presented symptom. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
    <description>A brief, clinician-administered test that helps determine the neuropsychological status of adults who have neurologic injury or disease such as dementia, head injury, and stroke. This tool consists of a battery of tests. Raw scores are transformed to a 0-120 scale, with a higher score indicating higher function. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Walking Distance</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
    <description>Clinician measures how far the individual can walk until fatigue requires him/her to stop. Longer distances demonstrate improvement. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Walking Speed</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
    <description>Assessed by timing the first 25 feet that the person walked. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>12-item MS Walking Scale (MSWS-12)</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
    <description>A 12-item self-report measure of the impact of MS on a person's walking. Raw scores are transformed to a 0-100 scale. A reduction in score indicates improvement. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Box &amp; Blocks (B&amp;B) Assessment - Right</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
    <description>A standardized clinical assessment of gross upper limb dexterity. Subjects move small blocks from one side of a box to the other within a time period (one minute). Each side is tested separately. The score is the number of blocks moved from 0-150. A higher score indicates improvement. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Box &amp; Blocks (B&amp;B) Assessment - Left</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
    <description>A standardized clinical assessment of gross upper limb dexterity. Subjects move small blocks from one side of a box to the other within a time period (one minute). Each side is tested separately. The score is the number of blocks moved from 0-150. A higher score indicates improvement. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multiple Sclerosis Impact Scale (MSIS-29) - Physical</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
    <description>A 29-item self-report tool that measures the impact of MS on day-to-day life. There are 3 scores, physical, psychological, and total score. Raw scores are transformed to a 0-100 scale. A higher score indicates a greater impact of disease on daily function. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Multiple Sclerosis Impact Scale (MSIS-29) - Psychological</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
    <description>A 29-item self-report tool that measures the impact of MS on day-to-day life. There are 3 scores, physical, psychological, and total score. Raw scores are transformed to a 0-100 scale. A higher score indicates a greater impact of disease on daily function. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Fatigue Impact Scale (MFIS)</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
    <description>A self-report tool that assesses the perceived impact of fatigue on daily activities. Consists of 21 items selected from the Fatigue Impact Scale. Scored on a 0-84 scale. A higher score indicates a greater impact of fatigue on daily activities. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Gross Motor Function Measure (GMFM)</measure>
    <time_frame>Change from Baseline at 6, 11, 16, 21 and 27 weeks</time_frame>
    <description>The GMFM a standardized observational instrument that measures change in gross motor function. Subscales include lying &amp; rolling; sitting; crawling &amp; kneeling; standing; and walking, running &amp; jumping. For the complete test, the raw scores are converted to a 0-100 scale, with higher scores indicating greater functional mobility. The items that we used were scored on a 0-3 scale and changes reported in percent improvement. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Slump Test</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
    <description>Measures and quantifies changes in trunk control during functional sitting. It was quickly determined that this test duplicated the TIS and was difficult to score objectively so the decision was made not to use it for the study. Performance-based and tested in participants who possessed the ability to perform the assessment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Modified Rivermead Mobility Index</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
    <description>An 8 item assessment that quantifies the ability to perform transfers. It has been validated in persons with stroke and a mixed neurologic population (43% MS). Score is a 0-40 scale. A higher score indicates higher function. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
  </secondary_outcome>
  <other_outcome>
    <measure>Video Nystagmography (VNG)</measure>
    <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
    <description>VNG is a standardized eye tracking test used to measure static and dynamic eye movement control to detect oculomotor abnormalities typically associated with degenerative neurological disorders, particularly in the brainstem and cerebellum. The subject wears goggles while an infrared video camera monitors and records eye movement as the eyes follow a dot on a computer screen.</description>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Multiple Sclerosis</condition>
  <arm_group>
    <arm_group_label>Neuromodulation Rehabilitation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Neuromodulation Rehabilitation</intervention_name>
    <description>CN-NINM uses sequenced patterns of electrical stimulation on the tongue. Our hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
    <arm_group_label>Neuromodulation Rehabilitation</arm_group_label>
    <other_name>Cranial Nerve Non-invasive Neuromodulation (CN-NINM)</other_name>
    <other_name>Portable Neuromodulation Stimulator (PoNS)</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Subjects must be age 18 or older.&#xD;
&#xD;
          -  Subjects will have a score between 6.5 to 7.5 on the Kurtzke Expanded Disability&#xD;
             Status Scale (EDSS). The EDSS is a method of quantifying disability in people with&#xD;
             multiple sclerosis.&#xD;
&#xD;
               -  Score of 6.5: needs constant bilateral support to walk 20 meters without resting.&#xD;
&#xD;
               -  Score of 7.0: unable to walk beyond five meters even with aid, and is essentially&#xD;
                  restricted to a wheelchair; wheels self and transfers alone, and is active in&#xD;
                  wheelchair about 12 hours a day.&#xD;
&#xD;
               -  Score of 7.5: unable to take more than a few steps and is restricted to&#xD;
                  wheelchair, and may need aid to transfer; wheels self, but may require a&#xD;
                  motorized chair for a full day's activities.&#xD;
&#xD;
          -  Subjects will have reached a plateau in an MS focused physical rehabilitation program&#xD;
             in the 6 months prior to enrollment.&#xD;
&#xD;
               -  Requiring prior physical therapy will ensure that subjects have a core level of&#xD;
                  function that will allow them to participate in the study.&#xD;
&#xD;
               -  Requiring that subjects have reached a plateau will ensure that subjects'&#xD;
                  response to the intervention is due to the use of the device and not to the&#xD;
                  physical exercises alone.&#xD;
&#xD;
               -  Subjects who have participated in a physical rehabilitation program demonstrate&#xD;
                  that they are willing and able to commit to a rigorous training regimen.&#xD;
&#xD;
          -  Subjects will have a maximum score of 20 on the Trunk Impairment Scale (TIS). The TIS&#xD;
             assesses static dynamic sitting balance and trunk coordination in a sitting position.&#xD;
             A score of 20 or lower indicates that their ability to adequately maintain sitting&#xD;
             posture is affected.&#xD;
&#xD;
          -  Subjects may have upper extremity involvement.&#xD;
&#xD;
          -  Subjects may have additional symptoms of nystagmus, dysarthria, sensory disturbance,&#xD;
             pain, and/or bowel and bladder function. As they present, we will use appropriate&#xD;
             assessments at baseline and successive study test points.&#xD;
&#xD;
          -  Subjects are their own legal guardians, and are able to understand and give informed&#xD;
             consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        Subjects will have no major co-morbidities, especially neurological disorders, uncontrolled&#xD;
        pain, hypertension or diabetes. All subjects, if on medications, will not have had any&#xD;
        major changes in type or dosage in within 3 months of enrollment. Additionally, candidates&#xD;
        will be excluded if they:&#xD;
&#xD;
          -  have Functional Systems Scores (FSS) 4 or greater for pyramidal, cerebellar,&#xD;
             brainstem, and sensory functions; 3 or greater for bowel and bladder function; and 2&#xD;
             or greater for cerebral function;&#xD;
&#xD;
          -  are able to walk independently;&#xD;
&#xD;
          -  use tobacco products (these activities tend to reduce tactile sensitivity in the oral&#xD;
             cavity);&#xD;
&#xD;
          -  have any oral abrasions, cuts, cold sores, piercings, tissue inflammation, or have had&#xD;
             oral surgery within the previous 3 months;&#xD;
&#xD;
          -  have a pacemaker, or are identified as at-risk for cardiovascular events;&#xD;
&#xD;
          -  have a history of seizures;&#xD;
&#xD;
          -  have a communicable disease;&#xD;
&#xD;
          -  have a biomechanical prosthetic;&#xD;
&#xD;
          -  are females who are pregnant.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Mitchell E Tyler, MS</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Wisconsin, Madison</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>TCNL, 455 Science Drive, Suite 165</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53711</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>June 2019</verification_date>
  <study_first_submitted>July 15, 2014</study_first_submitted>
  <study_first_submitted_qc>September 25, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 30, 2014</study_first_posted>
  <results_first_submitted>May 15, 2019</results_first_submitted>
  <results_first_submitted_qc>June 7, 2019</results_first_submitted_qc>
  <results_first_posted type="Actual">June 28, 2019</results_first_posted>
  <last_update_submitted>June 27, 2019</last_update_submitted>
  <last_update_submitted_qc>June 27, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">July 9, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>MS</keyword>
  <keyword>balance</keyword>
  <keyword>standing</keyword>
  <keyword>control</keyword>
  <keyword>movement</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
    <mesh_term>Sclerosis</mesh_term>
  </condition_browse>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Neuromodulation Rehabilitation</title>
          <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: Cranial-nerve non-invasive neuromodulation (CN-NINM) uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Neuromodulation Rehabilitation</title>
          <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="6"/>
          </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="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </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="5"/>
                  </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="1"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </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="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Disease Chronicity</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="17.7" spread="7.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>EDSS Score</title>
          <description>Participants with MS are assessed by a clinician using the Kurtzke Expanded Disability Status Scale (EDSS). Scores range 0-10 (higher numbers indicate greater disability). Participants scoring 1-4.5 can walk without aid, 5.0-7.0 are walking impaired, scores of 7.5+ indicate wheelchair restriction. EDSS draws on the Kurtzke Functional Systems Scores (FSS) that assess 7 physiologic systems affected by MS. FSS ranges from 0-10 in each subsystem, where higher numbers indicate greater levels of dysfunction. The resulting EDSS characterizes the overall ability of the individual.</description>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="7.0" spread="0.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>MS Subtype</title>
          <description>Secondary Progressing MS (SPMS) follows an initial Relapsing-Remitting (RRMS) diagnosis (~85 percent of initial MS diagnoses), characterized by relapses of increased disease activity and worsening symptoms, followed by remissions when the disease does not progress. SPMS is characterized as a gradual increase in disability as the disease progresses, with or without evidence of relapse or changes in an MRI scan. Primary Progressive MS (PPMS) is occurs in ~15 percent of initial MS diagnoses and presents as a steady progression of the disease with no clear relapses or remissions.</description>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>SPMS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>PPMS</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Trunk Impairment Scale (TIS)</title>
        <description>Static and dynamic sitting balance and trunk coordination are evaluated by a clinician. It is scored on a scale from 0-23, where the higher the score, the more improved the balance. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, and 21 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Trunk Impairment Scale (TIS)</title>
          <description>Static and dynamic sitting balance and trunk coordination are evaluated by a clinician. It is scored on a scale from 0-23, where the higher the score, the more improved the balance. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.63"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.06"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Static Standing Balance Test</title>
        <description>Clinician measures standing balance for up to 30 seconds in each of 5 conditions: feet 10 cm apart, feet together, stride stance, tandem stance, and single leg stance with eyes open and eyes closed. Total score is the sum of all 5 conditions. Higher scores indicate better balance. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Static Standing Balance Test</title>
          <description>Clinician measures standing balance for up to 30 seconds in each of 5 conditions: feet 10 cm apart, feet together, stride stance, tandem stance, and single leg stance with eyes open and eyes closed. Total score is the sum of all 5 conditions. Higher scores indicate better balance. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.57"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.90"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.49"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 27</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="0.32"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Impact of Visual Impairment Scale (IVIS)</title>
        <description>A 5-item self-report questionnaire that assesses the extent to which various activities dependent upon vision are affected by MS-related visual problems. Scores range from 0-15, with higher scores indicating a greater impact of visual problems on daily activities. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, and 21 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Impact of Visual Impairment Scale (IVIS)</title>
          <description>A 5-item self-report questionnaire that assesses the extent to which various activities dependent upon vision are affected by MS-related visual problems. Scores range from 0-15, with higher scores indicating a greater impact of visual problems on daily activities. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Medical Outcomes Study (MOS) Pain Effects Scale (PES)</title>
        <description>A self-report scale that assesses the ways in which pain and unpleasant sensation interfere with mood, ability to walk or move, sleep, work, recreation, and enjoyment of life. This assessment is used for subjects who have pain. Scores can range from 6-30. Items are scaled so that higher scores indicate a greater impact of pain on a patient's mood and behavior. Symptom specific test, only used for participants who presented symptom. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, and 21 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Medical Outcomes Study (MOS) Pain Effects Scale (PES)</title>
          <description>A self-report scale that assesses the ways in which pain and unpleasant sensation interfere with mood, ability to walk or move, sleep, work, recreation, and enjoyment of life. This assessment is used for subjects who have pain. Scores can range from 6-30. Items are scaled so that higher scores indicate a greater impact of pain on a patient's mood and behavior. Symptom specific test, only used for participants who presented symptom. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.55"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.64"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Bladder Control Scale (BLCS)</title>
        <description>A 4-item self-report scale to evaluate the impact of bladder control on lifestyle. This assessment is used for subjects with bladder issues. Scores can range from 0-22, with higher scores indicating greater bladder control problems. Symptom specific test, only used for participants who presented symptom. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Bladder Control Scale (BLCS)</title>
          <description>A 4-item self-report scale to evaluate the impact of bladder control on lifestyle. This assessment is used for subjects with bladder issues. Scores can range from 0-22, with higher scores indicating greater bladder control problems. Symptom specific test, only used for participants who presented symptom. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.30"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.62"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 27</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="0.27"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Bowel Control Scale (BWCS)</title>
        <description>A 5-item self-report scale to evaluate the impact of bowel control on lifestyle. This assessment is used for subjects with bowel issues. Scores can range from 0-26, with higher scores indicating greater bowel control problems. Symptom specific test, only used for participants who presented symptom. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Bowel Control Scale (BWCS)</title>
          <description>A 5-item self-report scale to evaluate the impact of bowel control on lifestyle. This assessment is used for subjects with bowel issues. Scores can range from 0-26, with higher scores indicating greater bowel control problems. Symptom specific test, only used for participants who presented symptom. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.68"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 27</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="0.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)</title>
        <description>A brief, clinician-administered test that helps determine the neuropsychological status of adults who have neurologic injury or disease such as dementia, head injury, and stroke. This tool consists of a battery of tests. Raw scores are transformed to a 0-120 scale, with a higher score indicating higher function. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)</title>
          <description>A brief, clinician-administered test that helps determine the neuropsychological status of adults who have neurologic injury or disease such as dementia, head injury, and stroke. This tool consists of a battery of tests. Raw scores are transformed to a 0-120 scale, with a higher score indicating higher function. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.39"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.78"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 27</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="0.51"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Walking Distance</title>
        <description>Clinician measures how far the individual can walk until fatigue requires him/her to stop. Longer distances demonstrate improvement. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Walking Distance</title>
          <description>Clinician measures how far the individual can walk until fatigue requires him/her to stop. Longer distances demonstrate improvement. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.76"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.69"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.67"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 27</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="0.26"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Walking Speed</title>
        <description>Assessed by timing the first 25 feet that the person walked. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Walking Speed</title>
          <description>Assessed by timing the first 25 feet that the person walked. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 27</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="-0.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>12-item MS Walking Scale (MSWS-12)</title>
        <description>A 12-item self-report measure of the impact of MS on a person's walking. Raw scores are transformed to a 0-100 scale. A reduction in score indicates improvement. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>12-item MS Walking Scale (MSWS-12)</title>
          <description>A 12-item self-report measure of the impact of MS on a person's walking. Raw scores are transformed to a 0-100 scale. A reduction in score indicates improvement. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 27</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="-0.42"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Box &amp; Blocks (B&amp;B) Assessment - Right</title>
        <description>A standardized clinical assessment of gross upper limb dexterity. Subjects move small blocks from one side of a box to the other within a time period (one minute). Each side is tested separately. The score is the number of blocks moved from 0-150. A higher score indicates improvement. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Box &amp; Blocks (B&amp;B) Assessment - Right</title>
          <description>A standardized clinical assessment of gross upper limb dexterity. Subjects move small blocks from one side of a box to the other within a time period (one minute). Each side is tested separately. The score is the number of blocks moved from 0-150. A higher score indicates improvement. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.52"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.45"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.47"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 27</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="4.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Box &amp; Blocks (B&amp;B) Assessment - Left</title>
        <description>A standardized clinical assessment of gross upper limb dexterity. Subjects move small blocks from one side of a box to the other within a time period (one minute). Each side is tested separately. The score is the number of blocks moved from 0-150. A higher score indicates improvement. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Box &amp; Blocks (B&amp;B) Assessment - Left</title>
          <description>A standardized clinical assessment of gross upper limb dexterity. Subjects move small blocks from one side of a box to the other within a time period (one minute). Each side is tested separately. The score is the number of blocks moved from 0-150. A higher score indicates improvement. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.07"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.50"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.04"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 27</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="0.00"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Multiple Sclerosis Impact Scale (MSIS-29) - Physical</title>
        <description>A 29-item self-report tool that measures the impact of MS on day-to-day life. There are 3 scores, physical, psychological, and total score. Raw scores are transformed to a 0-100 scale. A higher score indicates a greater impact of disease on daily function. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Multiple Sclerosis Impact Scale (MSIS-29) - Physical</title>
          <description>A 29-item self-report tool that measures the impact of MS on day-to-day life. There are 3 scores, physical, psychological, and total score. Raw scores are transformed to a 0-100 scale. A higher score indicates a greater impact of disease on daily function. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.61"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.89"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.46"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 27</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="-0.71"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Multiple Sclerosis Impact Scale (MSIS-29) - Psychological</title>
        <description>A 29-item self-report tool that measures the impact of MS on day-to-day life. There are 3 scores, physical, psychological, and total score. Raw scores are transformed to a 0-100 scale. A higher score indicates a greater impact of disease on daily function. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Multiple Sclerosis Impact Scale (MSIS-29) - Psychological</title>
          <description>A 29-item self-report tool that measures the impact of MS on day-to-day life. There are 3 scores, physical, psychological, and total score. Raw scores are transformed to a 0-100 scale. A higher score indicates a greater impact of disease on daily function. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.77"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.17"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.86"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.98"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.05"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 27</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="0.35"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Modified Fatigue Impact Scale (MFIS)</title>
        <description>A self-report tool that assesses the perceived impact of fatigue on daily activities. Consists of 21 items selected from the Fatigue Impact Scale. Scored on a 0-84 scale. A higher score indicates a greater impact of fatigue on daily activities. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Modified Fatigue Impact Scale (MFIS)</title>
          <description>A self-report tool that assesses the perceived impact of fatigue on daily activities. Consists of 21 items selected from the Fatigue Impact Scale. Scored on a 0-84 scale. A higher score indicates a greater impact of fatigue on daily activities. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.87"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="3.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.54"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.75"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.40"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 27</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="0.20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Gross Motor Function Measure (GMFM)</title>
        <description>The GMFM a standardized observational instrument that measures change in gross motor function. Subscales include lying &amp; rolling; sitting; crawling &amp; kneeling; standing; and walking, running &amp; jumping. For the complete test, the raw scores are converted to a 0-100 scale, with higher scores indicating greater functional mobility. The items that we used were scored on a 0-3 scale and changes reported in percent improvement. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 6, 11, 16, 21 and 27 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Gross Motor Function Measure (GMFM)</title>
          <description>The GMFM a standardized observational instrument that measures change in gross motor function. Subscales include lying &amp; rolling; sitting; crawling &amp; kneeling; standing; and walking, running &amp; jumping. For the complete test, the raw scores are converted to a 0-100 scale, with higher scores indicating greater functional mobility. The items that we used were scored on a 0-3 scale and changes reported in percent improvement. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.82"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.10"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.84"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 27</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="0.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Slump Test</title>
        <description>Measures and quantifies changes in trunk control during functional sitting. It was quickly determined that this test duplicated the TIS and was difficult to score objectively so the decision was made not to use it for the study. Performance-based and tested in participants who possessed the ability to perform the assessment.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
        <population>The Slump Test was ultimately not used because the investigators decided to use the TIS instead. The TIS was realized to be the more appropriate assessment of the two, and the investigators wanted to avoid both data redundancy and test fatigue</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Slump Test</title>
          <description>Measures and quantifies changes in trunk control during functional sitting. It was quickly determined that this test duplicated the TIS and was difficult to score objectively so the decision was made not to use it for the study. Performance-based and tested in participants who possessed the ability to perform the assessment.</description>
          <population>The Slump Test was ultimately not used because the investigators decided to use the TIS instead. The TIS was realized to be the more appropriate assessment of the two, and the investigators wanted to avoid both data redundancy and test fatigue</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Modified Rivermead Mobility Index</title>
        <description>An 8 item assessment that quantifies the ability to perform transfers. It has been validated in persons with stroke and a mixed neurologic population (43% MS). Score is a 0-40 scale. A higher score indicates higher function. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
        <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Modified Rivermead Mobility Index</title>
          <description>An 8 item assessment that quantifies the ability to perform transfers. It has been validated in persons with stroke and a mixed neurologic population (43% MS). Score is a 0-40 scale. A higher score indicates higher function. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a &quot;small&quot; effect size, 0.30 as a &quot;medium&quot; effect size, and 0.50 as a &quot;large&quot; effect size.</description>
          <population>Effect sizes from baseline reported for 4 subjects with EDSS 6.5 - 7.0. It was postulated that the physical limitations of two subjects with EDSS score of 7.5 presented special challenges to measuring changes in function with the available assessment mechanisms for this clinical population.</population>
          <units>percentage of change</units>
          <param>Number</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="4"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Baseline to Week 2</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.01"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 6</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.21"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 11</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 16</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="4"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.44"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 21</title>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="O1" value="3"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.15"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Baseline to Week 27</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="0.38"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Video Nystagmography (VNG)</title>
        <description>VNG is a standardized eye tracking test used to measure static and dynamic eye movement control to detect oculomotor abnormalities typically associated with degenerative neurological disorders, particularly in the brainstem and cerebellum. The subject wears goggles while an infrared video camera monitors and records eye movement as the eyes follow a dot on a computer screen.</description>
        <time_frame>Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks</time_frame>
        <population>The VNG was exploratory and opportunistic. The results are not available as the software to perform the quantitative data analysis is still under development.</population>
        <group_list>
          <group group_id="O1">
            <title>Neuromodulation Rehabilitation</title>
            <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
          </group>
        </group_list>
        <measure>
          <title>Video Nystagmography (VNG)</title>
          <description>VNG is a standardized eye tracking test used to measure static and dynamic eye movement control to detect oculomotor abnormalities typically associated with degenerative neurological disorders, particularly in the brainstem and cerebellum. The subject wears goggles while an infrared video camera monitors and records eye movement as the eyes follow a dot on a computer screen.</description>
          <population>The VNG was exploratory and opportunistic. The results are not available as the software to perform the quantitative data analysis is still under development.</population>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
              </count_list>
            </analyzed>
          </analyzed_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <group_list>
        <group group_id="E1">
          <title>Neuromodulation Rehabilitation</title>
          <description>Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.&#xD;
Neuromodulation Rehabilitation: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. The hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.</description>
        </group>
      </group_list>
      <serious_events>
        <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="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="6" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Viral Infection</sub_title>
                <counts group_id="E1" events="2" subjects_affected="2" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Injury, poisoning and procedural complications</title>
            <event_list>
              <event>
                <sub_title>Injury</sub_title>
                <description>Superficial abrasion on both her right forearm during a follow-up visit to the lab.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Osteoarthritis Pain</sub_title>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Trigeminal Neuralgia (TN)</sub_title>
                <description>The subject reported that the stimulation seemed to ease the symptoms of TN when she resumed training</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="6"/>
              </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>Dr. Mitchell Tyler</name_or_title>
      <organization>University of Wisconsin - Madison</organization>
      <phone>(608) 262-5112</phone>
      <email>metyler1@wisc.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/NCT02252666
org study id: 2013-1060
nct id: NCT02252666
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
The investigators hypothesis is that electrical stimulation to the tongue that directly
      stimulates two cranial nerve nuclei (Trigeminal and Facial Nerve Nuclei), will excite neural
      impulses to the brainstem and cerebellum. The investigators call this cranial nerve
      non-invasive neuromodulation (CN-NINM). The activation of these structures induces
      neuroplasticity when combined with specific physical exercises, can reduce symptoms of
      advanced MS, targeting primarily postural stability (sitting and standing), upper extremity
      movement, and ability to perform self-transfers.
The intervention will be similar to that used in the investigators previous work with
      movement disorders, and will be tailored to the address issues unique to individuals with
      advanced MS.

      The study will enroll a total of 6 subjects having advanced MS that present with significant
      seated and standing balance, posture, or movement control deficits due to MS.

      Subjects will complete twice-daily lab training for two weeks (5 days/week). Each lab
      training (morning and afternoon) includes 1.5 to 2 hours of instruction in balance, posture
      and gait activities; therapeutic exercise for isolated muscle control; transfer training; and
      relaxation training.

      Activities are performed in 20-minute sessions with concomitant electrical stimulation of the
      tongue. The intervention is customized according to each subject's particular symptoms and
      tolerance. If a subject is not able to perform this amount of training, the training will be
      adapted to a level that is tolerable.

      After these 2 weeks, subjects will continue to perform these same intervention activities at
      home for 4 weeks. They will return to the lab for 1 week of training and testing, then
      perform home training for 4 weeks. This cycle is repeated for a total of 5 cycles.

      After the 6 months have been completed, subjects may choose to participate in an optional
      second phase of the study. The second phase includes an additional 12 months of participation
      in which subjects perform the intervention activities at home training and return to the lab
      on time per month for 2 hours of testing and 2 hours of training.

      If successful, this study would indicate that CN-NINM intervention may reduce the symptoms of
      advanced MS.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Trunk Impairment Scale (TIS)
time frame: Change from Baseline at 2, 6, 11, 16, and 21 weeks
description: Static and dynamic sitting balance and trunk coordination are evaluated by a clinician. It is scored on a scale from 0-23, where the higher the score, the more improved the balance. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: Static Standing Balance Test
time frame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
description: Clinician measures standing balance for up to 30 seconds in each of 5 conditions: feet 10 cm apart, feet together, stride stance, tandem stance, and single leg stance with eyes open and eyes closed. Total score is the sum of all 5 conditions. Higher scores indicate better balance. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: Impact of Visual Impairment Scale (IVIS)
time frame: Change from Baseline at 2, 6, 11, 16, and 21 weeks
description: A 5-item self-report questionnaire that assesses the extent to which various activities dependent upon vision are affected by MS-related visual problems. Scores range from 0-15, with higher scores indicating a greater impact of visual problems on daily activities. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: Medical Outcomes Study (MOS) Pain Effects Scale (PES)
time frame: Change from Baseline at 2, 6, 11, 16, and 21 weeks
description: A self-report scale that assesses the ways in which pain and unpleasant sensation interfere with mood, ability to walk or move, sleep, work, recreation, and enjoyment of life. This assessment is used for subjects who have pain. Scores can range from 6-30. Items are scaled so that higher scores indicate a greater impact of pain on a patient's mood and behavior. Symptom specific test, only used for participants who presented symptom. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: Bladder Control Scale (BLCS)
time frame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
description: A 4-item self-report scale to evaluate the impact of bladder control on lifestyle. This assessment is used for subjects with bladder issues. Scores can range from 0-22, with higher scores indicating greater bladder control problems. Symptom specific test, only used for participants who presented symptom. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: Bowel Control Scale (BWCS)
time frame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
description: A 5-item self-report scale to evaluate the impact of bowel control on lifestyle. This assessment is used for subjects with bowel issues. Scores can range from 0-26, with higher scores indicating greater bowel control problems. Symptom specific test, only used for participants who presented symptom. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: Repeatable Battery for the Assessment of Neuropsychological Status (RBANS)
time frame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
description: A brief, clinician-administered test that helps determine the neuropsychological status of adults who have neurologic injury or disease such as dementia, head injury, and stroke. This tool consists of a battery of tests. Raw scores are transformed to a 0-120 scale, with a higher score indicating higher function. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: Walking Distance
time frame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
description: Clinician measures how far the individual can walk until fatigue requires him/her to stop. Longer distances demonstrate improvement. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: Walking Speed
time frame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
description: Assessed by timing the first 25 feet that the person walked. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: 12-item MS Walking Scale (MSWS-12)
time frame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
description: A 12-item self-report measure of the impact of MS on a person's walking. Raw scores are transformed to a 0-100 scale. A reduction in score indicates improvement. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: Box & Blocks (B&B) Assessment - Right
time frame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
description: A standardized clinical assessment of gross upper limb dexterity. Subjects move small blocks from one side of a box to the other within a time period (one minute). Each side is tested separately. The score is the number of blocks moved from 0-150. A higher score indicates improvement. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: Box & Blocks (B&B) Assessment - Left
time frame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
description: A standardized clinical assessment of gross upper limb dexterity. Subjects move small blocks from one side of a box to the other within a time period (one minute). Each side is tested separately. The score is the number of blocks moved from 0-150. A higher score indicates improvement. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: Multiple Sclerosis Impact Scale (MSIS-29) - Physical
time frame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
description: A 29-item self-report tool that measures the impact of MS on day-to-day life. There are 3 scores, physical, psychological, and total score. Raw scores are transformed to a 0-100 scale. A higher score indicates a greater impact of disease on daily function. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: Multiple Sclerosis Impact Scale (MSIS-29) - Psychological
time frame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
description: A 29-item self-report tool that measures the impact of MS on day-to-day life. There are 3 scores, physical, psychological, and total score. Raw scores are transformed to a 0-100 scale. A higher score indicates a greater impact of disease on daily function. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: Modified Fatigue Impact Scale (MFIS)
time frame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
description: A self-report tool that assesses the perceived impact of fatigue on daily activities. Consists of 21 items selected from the Fatigue Impact Scale. Scored on a 0-84 scale. A higher score indicates a greater impact of fatigue on daily activities. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: Gross Motor Function Measure (GMFM)
time frame: Change from Baseline at 6, 11, 16, 21 and 27 weeks
description: The GMFM a standardized observational instrument that measures change in gross motor function. Subscales include lying & rolling; sitting; crawling & kneeling; standing; and walking, running & jumping. For the complete test, the raw scores are converted to a 0-100 scale, with higher scores indicating greater functional mobility. The items that we used were scored on a 0-3 scale and changes reported in percent improvement. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: Slump Test
time frame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
description: Measures and quantifies changes in trunk control during functional sitting. It was quickly determined that this test duplicated the TIS and was difficult to score objectively so the decision was made not to use it for the study. Performance-based and tested in participants who possessed the ability to perform the assessment.
measure: Modified Rivermead Mobility Index
time frame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
description: An 8 item assessment that quantifies the ability to perform transfers. It has been validated in persons with stroke and a mixed neurologic population (43% MS). Score is a 0-40 scale. A higher score indicates higher function. Performance-based and tested in participants who possessed the ability to perform the assessment. Effect size is reported (quantified difference between baseline and time point). The larger the absolute value, the stronger the effect. Cohen's guidelines for social sciences indicate 0.10 as a "small" effect size, 0.30 as a "medium" effect size, and 0.50 as a "large" effect size.
measure: Video Nystagmography (VNG)
time frame: Change from Baseline at 2, 6, 11, 16, 21 and 27 weeks
description: VNG is a standardized eye tracking test used to measure static and dynamic eye movement control to detect oculomotor abnormalities typically associated with degenerative neurological disorders, particularly in the brainstem and cerebellum. The subject wears goggles while an infrared video camera monitors and records eye movement as the eyes follow a dot on a computer screen.
arm group label: Neuromodulation Rehabilitation
arm group type: Experimental
description: Balance, posture and gait activities; therapeutic exercise for isolated muscle control; transfer training; and relaxation training using neurostimulation modulation. 2-week in lab intervention training, training at home and periodic return for follow-up testing and instruction on the next phase of the intervention.
intervention type: Device
intervention name: Neuromodulation Rehabilitation
description: CN-NINM uses sequenced patterns of electrical stimulation on the tongue. Our hypothesis is that CN-NINM induces neuroplasticity by noninvasive stimulation of two major cranial nerves: trigeminal, CN-V, and facial, CN-VII.
arm group label: Neuromodulation Rehabilitation
other name: Cranial Nerve Non-invasive Neuromodulation (CN-NINM)
other name: Portable Neuromodulation Stimulator (PoNS)
criteria: 
gender: All
minimum age: 18 Years
maximum age: 90 Years
healthy volunteers: No
last name: Mitchell E Tyler, MS
role: Principal Investigator
affiliation: University of Wisconsin, Madison
facility: 
country: United States
responsible party type: Sponsor
mesh term: Multiple Sclerosis
mesh term: Sclerosis
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 