<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/NCT03240601</url>
  </required_header>
  <id_info>
    <org_study_id>696</org_study_id>
    <nct_id>NCT03240601</nct_id>
  </id_info>
  <brief_title>Spinal Cord Stimulation to Augment Activity Based Therapy</brief_title>
  <official_title>Combined Influence of Transcutaneous Spinal Cord Stimulation and Locomotor Training on Spasticity and Walking Outcomes After Spinal Cord Injury</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shepherd Center, Atlanta GA</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Foundation Wings For Life</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shepherd Center, Atlanta GA</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Involuntary muscle activity, often called spasticity, is a common problem following spinal&#xD;
      cord injury (SCI) that can make it hard to move. Many things can cause spasticity including:&#xD;
      muscle stretch, movement, or it can happen for no reason, and it is often described as an&#xD;
      uncontrolled muscle spasm or feeling of stiffness. Drugs are typically used to treat&#xD;
      spasticity, but they often have side effects, like muscle weakness, which can add to movement&#xD;
      problems. Rehabilitation therapies offer alternatives to drugs for treating involuntary&#xD;
      muscle activity, and rehabilitation can also improve daily function and quality of life.&#xD;
      These benefits may be greater when several rehabilitation therapies are used together.&#xD;
&#xD;
      Walking ability can be improved with a type of therapy called &quot;locomotor training&quot;. This type&#xD;
      of therapy may also have the benefit of decreasing spasticity. When locomotor training (LT)&#xD;
      is combined with electrical stimulation, the benefits of training may be increased. In this&#xD;
      study, investigators will use a kind of stimulation called transcutaneous spinal cord&#xD;
      stimulation (&quot;TSS&quot;) to stimulate participants' spinal cord nerves during locomotor training.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Involuntary muscle activity, often referred to as spasticity, is a common problem following&#xD;
      spinal cord injury. Spasticity can be evoked by stimuli or occur spontaneously, and it can&#xD;
      manifest as spasms, clonus, or the stiffness associated with hypertonia. While medications&#xD;
      are typically used to treat the general symptoms of spasticity, they often have additional&#xD;
      side effects, like muscle weakness, that can impede rehabilitation. Physical therapeutics&#xD;
      offer an alternative to these drug treatments, but the most effective therapeutic strategy&#xD;
      for managing spasticity has not yet been identified. A combination of physical therapeutics&#xD;
      may provide the best strategy for managing spasticity while also improving general motor&#xD;
      control for functional movements.&#xD;
&#xD;
      Walking ability can be improved through locomotor training, which has also been shown to&#xD;
      reduce spasticity. When locomotor training is combined with electrical stimulation, the&#xD;
      benefits of training may be increased. To investigate the potential benefits of this&#xD;
      combinatorial treatment strategy, investigators will use a kind of electrical stimulation&#xD;
      called transcutaneous spinal cord stimulation (&quot;TSS&quot;) to stimulate spinal cord nerves during&#xD;
      locomotor training.&#xD;
&#xD;
      In order to facilitate the translation of study findings into clinical practice, this study&#xD;
      uses a pragmatic design, meaning that the study will involve the use of real world clinical&#xD;
      settings and practices. Participants will undergo their standard physical therapist directed&#xD;
      locomotor training program while receiving transcutaneous spinal cord stimulation (TSS) as an&#xD;
      additional treatment. The effects of locomotor training alone will be compared to the&#xD;
      combination of locomotor training with TSS, specifically comparing the effects of these&#xD;
      treatments on spasticity and walking function.&#xD;
&#xD;
      Investigators expect that the combination of TSS with locomotor training will provide 1) a&#xD;
      greater reduction in spasticity and 2) a greater improvement of walking function compared to&#xD;
      locomotor training alone.&#xD;
&#xD;
      The findings from this study have the potential to rapidly facilitate the translation of a&#xD;
      novel combination treatment for the management of spasticity and improvement of walking&#xD;
      function into real world clinical practice.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 1, 2017</start_date>
  <completion_date type="Actual">September 11, 2019</completion_date>
  <primary_completion_date type="Actual">September 11, 2019</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Triple (Participant, Care Provider, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Walking Function - 10m Walk Walking Speed (m/s)</measure>
    <time_frame>Change in 10m Walk Speed (m/s) during the Intervention Phase (Week 2 test to Week 4 test)</time_frame>
    <description>You will walk over a mat that contains sensors to measure your walking speed as well as wear motion tracking sensors. You will be allowed to use whatever assistive devices you typically use (e.g., braces, walker, forearm crutches). In addition to walking speed, we will also assess your gait kinematics.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Spasticity - Pendulum Test</measure>
    <time_frame>Pendulum angle (degrees) change during the Intervention Phase (Week 2 test to Week 4 test)</time_frame>
    <description>This test measures the amount of spasticity in your leg muscles. You will sit at the edge of a mat with your lower legs hanging over the edge of the mat. Motion capture sensors (Xsens) will be placed on both of your legs to record changes in your knee joint angles when your leg is dropped. The examiner will straighten your leg and then allow it to drop and swing over the edge of the mat. The angle of your knee and the movement of your leg will be recorded as it drops. This will be performed three times for each leg separately.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Walking Function - 2 Minute Walk</measure>
    <time_frame>2 Minute Walk test (distance) change during the Intervention Phase (Week 2 test to Week 4 test)</time_frame>
    <description>You will walk for 2 minutes overground and we will measure how far you walk.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Spasticity - Ankle Clonus Drop Test</measure>
    <time_frame>Change in number of clonic ankle oscillations elicited via Ankle Clonus Drop Test during the Intervention Phase (Week 2 test to Week 4 test)</time_frame>
    <description>This test measures the amount of spasticity in your ankle. We will use the motion capture sensors to record your ankle joint angles. For this test you will sit upright. Your leg will be raised to 10cm above the rest position and released allowing the front of your foot to land on the edge of a box. The angle bouncing movement of your foot (clonus) will be recorded as it drops and catches on the box. This will be performed three times for each leg separately. Full details of test methods can be found at: Manella, Roach, and Field-Fote. Temporal Indices of Ankle Clonus and Relationship to Electrophysiologic and Clinical Measures in Persons With Spinal Cord Injury. J Neurol Phys Ther. 2017 Oct;41(4):229-238.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Spasticity - Muscle Co-contraction During Voluntary Activation</measure>
    <time_frame>Co-contraction change during the Intervention Phase (Week 2 test to Week 4 test)</time_frame>
    <description>Muscle activity will be recorded using electromyography (EMG) during activities where you move your legs, and activities where your legs are moved by the examiner. Electrodes will be placed on four muscles of your legs (front and back of your thigh and lower leg), you will be asked to move your ankles and extend your legs while we record your muscle activity. We will test whether the EMG is activated in only one muscle (isolated) when you try to activate that muscle, or whether muscles that you are not trying to activate are also activated at the same time (co-contraction)</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Spasticity - Spinal Cord Assessment Tool for Spastic Reflexes (SCATS) Test</measure>
    <time_frame>SCATS scores change during the Intervention Phase (Week 2 test to Week 4 test)</time_frame>
    <description>A trained therapist will perform the SCATS assessment before and after each training session. SCATS assesses 3 aspects of spasticity: clonus, flexor spasms, extensor spasms in response to perturbation. Scores range from 0-3 as follows: 0 = no reaction; 1 = mild, &lt;3 sec response; 2 = moderate, 3-10 sec response; 3 = severe, &gt;10 sec response</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Stimulation Tolerability</measure>
    <time_frame>Numerical rating scale of painfulness of stimulation in stimulation group only during stimulation weeks only (weeks 3 and 4)</time_frame>
    <description>Using a 0-10 numerical rating scale (NRS) for pain, you will be asked your perception of pain during the final 2 weeks of stimulation. NRS anchors are 0 = no pain, 10 = pain as bad as you can imagine</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">18</enrollment>
  <condition>Transcutaneous Spinal Stimulation</condition>
  <condition>Walking</condition>
  <condition>Spasticity</condition>
  <condition>Human</condition>
  <condition>Spinal Cord Injuries</condition>
  <arm_group>
    <arm_group_label>Subthreshold</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will briefly ramp up to the lowest intensity that is first detected by the participant and then ramped down to a level no longer detected by the participant. Participants will continue their locomotor training.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Active</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will ramp up slowly to a level that produces parasthesia (tingling) throughout the lower extremity. This intensity will be applied for 30 minutes while participants continue their locomotor training.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcutaneous spinal stimulation</intervention_name>
    <description>For TSS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
    <arm_group_label>Active</arm_group_label>
    <arm_group_label>Subthreshold</arm_group_label>
    <other_name>TSS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ability and willingness to consent and/or authorize use of protected health&#xD;
             information&#xD;
&#xD;
          -  Be between 18-65 years of age&#xD;
&#xD;
          -  Be enrolled in Spinal Cord Injury In-Patient or Day Program at the Shepherd Center&#xD;
&#xD;
          -  Be eligible for locomotor training at the Shepherd Center&#xD;
&#xD;
          -  Be able to take a step, with or without an assistive device&#xD;
&#xD;
          -  Have a spinal cord injury, completed in-patient rehabilitation, and have been&#xD;
             discharged to home&#xD;
&#xD;
          -  Have at least mild &quot;spasticity&quot; affecting leg muscles&#xD;
&#xD;
          -  You may participate if you use prescription medications, including baclofen for&#xD;
             control of spasticity&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Inability or unwillingness to consent and/or authorization for use of protected health&#xD;
             information&#xD;
&#xD;
          -  Progressive or potentially progressive spinal lesions, including degenerative, or&#xD;
             progressive vascular disorders of the spine and/or spinal cord&#xD;
&#xD;
          -  Neurologic level at or below spinal level T12&#xD;
&#xD;
          -  History of cardiovascular irregularities&#xD;
&#xD;
          -  Problems with following instructions&#xD;
&#xD;
          -  Orthopedic problems that would limit your participation in the protocol (e.g. knee or&#xD;
             hip flexion contractures of greater than 10 degrees)&#xD;
&#xD;
          -  Women who are pregnant, or who have reason to believe they are or may become pregnant&#xD;
             due to unknown risks to the fetus associated with tcSCS&#xD;
&#xD;
          -  Persons who have implanted stimulators/electronic devices of any type will be excluded&#xD;
             due to unknown potential of tcSCS effects&#xD;
&#xD;
          -  Active infection of any type, as infection may exacerbate spasticity resulting in&#xD;
             inability to identify the influence of the treatment&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Edelle C Field-Fote, PT, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Shepherd Center, Inc</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Shepherd Center, Inc.</name>
      <address>
        <city>Atlanta</city>
        <state>Georgia</state>
        <zip>30309</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>December 2021</verification_date>
  <study_first_submitted>July 17, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 7, 2017</study_first_posted>
  <results_first_submitted>March 8, 2021</results_first_submitted>
  <results_first_submitted_qc>December 30, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">January 25, 2022</results_first_posted>
  <last_update_submitted>December 30, 2021</last_update_submitted>
  <last_update_submitted_qc>December 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">January 25, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscle Spasticity</mesh_term>
    <mesh_term>Spinal Cord Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>December 28, 2021</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/01/NCT03240601/Prot_SAP_002.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Subthreshold</title>
          <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will briefly ramp up to the lowest intensity that is first detected by the participant and then ramped down to a level no longer detected by the participant. Participants will continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
        </group>
        <group group_id="P2">
          <title>Active</title>
          <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will ramp up slowly to a level that produces parasthesia (tingling) throughout the lower extremity. This intensity will be applied for 30 minutes while participants continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="9"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="8"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="1"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Subthreshold</title>
          <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will briefly ramp up to the lowest intensity that is first detected by the participant and then ramped down to a level no longer detected by the participant. Participants will continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
        </group>
        <group group_id="B2">
          <title>Active</title>
          <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will ramp up slowly to a level that produces parasthesia (tingling) throughout the lower extremity. This intensity will be applied for 30 minutes while participants continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
        </group>
        <group group_id="B3">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="9"/>
            <count group_id="B2" value="9"/>
            <count group_id="B3" value="18"/>
          </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="13"/>
                  </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 group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="8"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="4"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="9"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Walking Function - 10m Walk Walking Speed (m/s)</title>
        <description>You will walk over a mat that contains sensors to measure your walking speed as well as wear motion tracking sensors. You will be allowed to use whatever assistive devices you typically use (e.g., braces, walker, forearm crutches). In addition to walking speed, we will also assess your gait kinematics.</description>
        <time_frame>Change in 10m Walk Speed (m/s) during the Intervention Phase (Week 2 test to Week 4 test)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Subthreshold</title>
            <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will briefly ramp up to the lowest intensity that is first detected by the participant and then ramped down to a level no longer detected by the participant. Participants will continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
          </group>
          <group group_id="O2">
            <title>Active</title>
            <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will ramp up slowly to a level that produces parasthesia (tingling) throughout the lower extremity. This intensity will be applied for 30 minutes while participants continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Walking Function - 10m Walk Walking Speed (m/s)</title>
          <description>You will walk over a mat that contains sensors to measure your walking speed as well as wear motion tracking sensors. You will be allowed to use whatever assistive devices you typically use (e.g., braces, walker, forearm crutches). In addition to walking speed, we will also assess your gait kinematics.</description>
          <units>speed difference in meters per second</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0.06" spread="0.08"/>
                    <measurement group_id="O2" value="0.16" spread="0.13"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Change in Spasticity - Pendulum Test</title>
        <description>This test measures the amount of spasticity in your leg muscles. You will sit at the edge of a mat with your lower legs hanging over the edge of the mat. Motion capture sensors (Xsens) will be placed on both of your legs to record changes in your knee joint angles when your leg is dropped. The examiner will straighten your leg and then allow it to drop and swing over the edge of the mat. The angle of your knee and the movement of your leg will be recorded as it drops. This will be performed three times for each leg separately.</description>
        <time_frame>Pendulum angle (degrees) change during the Intervention Phase (Week 2 test to Week 4 test)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Subthreshold</title>
            <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will briefly ramp up to the lowest intensity that is first detected by the participant and then ramped down to a level no longer detected by the participant. Participants will continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
          </group>
          <group group_id="O2">
            <title>Active</title>
            <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will ramp up slowly to a level that produces parasthesia (tingling) throughout the lower extremity. This intensity will be applied for 30 minutes while participants continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Spasticity - Pendulum Test</title>
          <description>This test measures the amount of spasticity in your leg muscles. You will sit at the edge of a mat with your lower legs hanging over the edge of the mat. Motion capture sensors (Xsens) will be placed on both of your legs to record changes in your knee joint angles when your leg is dropped. The examiner will straighten your leg and then allow it to drop and swing over the edge of the mat. The angle of your knee and the movement of your leg will be recorded as it drops. This will be performed three times for each leg separately.</description>
          <units>Change in Angle (degrees)</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" spread="13"/>
                    <measurement group_id="O2" value="7" spread="19"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Walking Function - 2 Minute Walk</title>
        <description>You will walk for 2 minutes overground and we will measure how far you walk.</description>
        <time_frame>2 Minute Walk test (distance) change during the Intervention Phase (Week 2 test to Week 4 test)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Subthreshold</title>
            <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will briefly ramp up to the lowest intensity that is first detected by the participant and then ramped down to a level no longer detected by the participant. Participants will continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
          </group>
          <group group_id="O2">
            <title>Active</title>
            <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will ramp up slowly to a level that produces parasthesia (tingling) throughout the lower extremity. This intensity will be applied for 30 minutes while participants continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Walking Function - 2 Minute Walk</title>
          <description>You will walk for 2 minutes overground and we will measure how far you walk.</description>
          <units>meters</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" spread=".03"/>
                    <measurement group_id="O2" value="15" spread=".12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Spasticity - Ankle Clonus Drop Test</title>
        <description>This test measures the amount of spasticity in your ankle. We will use the motion capture sensors to record your ankle joint angles. For this test you will sit upright. Your leg will be raised to 10cm above the rest position and released allowing the front of your foot to land on the edge of a box. The angle bouncing movement of your foot (clonus) will be recorded as it drops and catches on the box. This will be performed three times for each leg separately. Full details of test methods can be found at: Manella, Roach, and Field-Fote. Temporal Indices of Ankle Clonus and Relationship to Electrophysiologic and Clinical Measures in Persons With Spinal Cord Injury. J Neurol Phys Ther. 2017 Oct;41(4):229-238.</description>
        <time_frame>Change in number of clonic ankle oscillations elicited via Ankle Clonus Drop Test during the Intervention Phase (Week 2 test to Week 4 test)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Subthreshold</title>
            <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will briefly ramp up to the lowest intensity that is first detected by the participant and then ramped down to a level no longer detected by the participant. Participants will continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
          </group>
          <group group_id="O2">
            <title>Active</title>
            <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will ramp up slowly to a level that produces parasthesia (tingling) throughout the lower extremity. This intensity will be applied for 30 minutes while participants continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Spasticity - Ankle Clonus Drop Test</title>
          <description>This test measures the amount of spasticity in your ankle. We will use the motion capture sensors to record your ankle joint angles. For this test you will sit upright. Your leg will be raised to 10cm above the rest position and released allowing the front of your foot to land on the edge of a box. The angle bouncing movement of your foot (clonus) will be recorded as it drops and catches on the box. This will be performed three times for each leg separately. Full details of test methods can be found at: Manella, Roach, and Field-Fote. Temporal Indices of Ankle Clonus and Relationship to Electrophysiologic and Clinical Measures in Persons With Spinal Cord Injury. J Neurol Phys Ther. 2017 Oct;41(4):229-238.</description>
          <units>change in clonic oscillations</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" spread="7"/>
                    <measurement group_id="O2" value="1" spread="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Spasticity - Muscle Co-contraction During Voluntary Activation</title>
        <description>Muscle activity will be recorded using electromyography (EMG) during activities where you move your legs, and activities where your legs are moved by the examiner. Electrodes will be placed on four muscles of your legs (front and back of your thigh and lower leg), you will be asked to move your ankles and extend your legs while we record your muscle activity. We will test whether the EMG is activated in only one muscle (isolated) when you try to activate that muscle, or whether muscles that you are not trying to activate are also activated at the same time (co-contraction)</description>
        <time_frame>Co-contraction change during the Intervention Phase (Week 2 test to Week 4 test)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Subthreshold</title>
            <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will briefly ramp up to the lowest intensity that is first detected by the participant and then ramped down to a level no longer detected by the participant. Participants will continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
          </group>
          <group group_id="O2">
            <title>Active</title>
            <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will ramp up slowly to a level that produces parasthesia (tingling) throughout the lower extremity. This intensity will be applied for 30 minutes while participants continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Spasticity - Muscle Co-contraction During Voluntary Activation</title>
          <description>Muscle activity will be recorded using electromyography (EMG) during activities where you move your legs, and activities where your legs are moved by the examiner. Electrodes will be placed on four muscles of your legs (front and back of your thigh and lower leg), you will be asked to move your ankles and extend your legs while we record your muscle activity. We will test whether the EMG is activated in only one muscle (isolated) when you try to activate that muscle, or whether muscles that you are not trying to activate are also activated at the same time (co-contraction)</description>
          <units>change in co-contraction ratio</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1" spread="3"/>
                    <measurement group_id="O2" value="1" spread="3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Spasticity - Spinal Cord Assessment Tool for Spastic Reflexes (SCATS) Test</title>
        <description>A trained therapist will perform the SCATS assessment before and after each training session. SCATS assesses 3 aspects of spasticity: clonus, flexor spasms, extensor spasms in response to perturbation. Scores range from 0-3 as follows: 0 = no reaction; 1 = mild, &lt;3 sec response; 2 = moderate, 3-10 sec response; 3 = severe, &gt;10 sec response</description>
        <time_frame>SCATS scores change during the Intervention Phase (Week 2 test to Week 4 test)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Subthreshold</title>
            <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will briefly ramp up to the lowest intensity that is first detected by the participant and then ramped down to a level no longer detected by the participant. Participants will continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
          </group>
          <group group_id="O2">
            <title>Active</title>
            <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will ramp up slowly to a level that produces parasthesia (tingling) throughout the lower extremity. This intensity will be applied for 30 minutes while participants continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Spasticity - Spinal Cord Assessment Tool for Spastic Reflexes (SCATS) Test</title>
          <description>A trained therapist will perform the SCATS assessment before and after each training session. SCATS assesses 3 aspects of spasticity: clonus, flexor spasms, extensor spasms in response to perturbation. Scores range from 0-3 as follows: 0 = no reaction; 1 = mild, &lt;3 sec response; 2 = moderate, 3-10 sec response; 3 = severe, &gt;10 sec response</description>
          <units>change in SCI-SET score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="8"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="0" spread="2"/>
                    <measurement group_id="O2" value="0" spread="2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Stimulation Tolerability</title>
        <description>Using a 0-10 numerical rating scale (NRS) for pain, you will be asked your perception of pain during the final 2 weeks of stimulation. NRS anchors are 0 = no pain, 10 = pain as bad as you can imagine</description>
        <time_frame>Numerical rating scale of painfulness of stimulation in stimulation group only during stimulation weeks only (weeks 3 and 4)</time_frame>
        <population>Only the LT+TSS group received active stimulation, tolerability was assessed only in this group</population>
        <group_list>
          <group group_id="O1">
            <title>Subthreshold</title>
            <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will briefly ramp up to the lowest intensity that is first detected by the participant and then ramped down to a level no longer detected by the participant. Participants will continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
          </group>
          <group group_id="O2">
            <title>Active</title>
            <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will ramp up slowly to a level that produces parasthesia (tingling) throughout the lower extremity. This intensity will be applied for 30 minutes while participants continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
          </group>
        </group_list>
        <measure>
          <title>Stimulation Tolerability</title>
          <description>Using a 0-10 numerical rating scale (NRS) for pain, you will be asked your perception of pain during the final 2 weeks of stimulation. NRS anchors are 0 = no pain, 10 = pain as bad as you can imagine</description>
          <population>Only the LT+TSS group received active stimulation, tolerability was assessed only in this group</population>
          <units>Scores on a 1-10 scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="0"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O2" value="3" spread="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>4 weeks</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Subthreshold</title>
          <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will briefly ramp up to the lowest intensity that is first detected by the participant and then ramped down to a level no longer detected by the participant. Participants will continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</description>
        </group>
        <group group_id="E2">
          <title>Active</title>
          <description>Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will ramp up slowly to a level that produces parasthesia (tingling) throughout the lower extremity. This intensity will be applied for 30 minutes while participants continue their locomotor training.&#xD;
Transcutaneous spinal cord stimulation: For tcSCS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.</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="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>1</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="9"/>
              </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. Edelle Field-Fote</name_or_title>
      <organization>Shepherd Center</organization>
      <phone>4046034274</phone>
      <email>edelle.field-fote@shepherd.org</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/NCT03240601
org study id: 696
nct id: NCT03240601
lead sponsor: 
collaborator: 
is fda regulated drug: No
is fda regulated device: Yes
Involuntary muscle activity, often called spasticity, is a common problem following spinal
      cord injury (SCI) that can make it hard to move. Many things can cause spasticity including:
      muscle stretch, movement, or it can happen for no reason, and it is often described as an
      uncontrolled muscle spasm or feeling of stiffness. Drugs are typically used to treat
      spasticity, but they often have side effects, like muscle weakness, which can add to movement
      problems. Rehabilitation therapies offer alternatives to drugs for treating involuntary
      muscle activity, and rehabilitation can also improve daily function and quality of life.
      These benefits may be greater when several rehabilitation therapies are used together.

      Walking ability can be improved with a type of therapy called "locomotor training". This type
      of therapy may also have the benefit of decreasing spasticity. When locomotor training (LT)
      is combined with electrical stimulation, the benefits of training may be increased. In this
      study, investigators will use a kind of stimulation called transcutaneous spinal cord
      stimulation ("TSS") to stimulate participants' spinal cord nerves during locomotor training.
Involuntary muscle activity, often referred to as spasticity, is a common problem following
      spinal cord injury. Spasticity can be evoked by stimuli or occur spontaneously, and it can
      manifest as spasms, clonus, or the stiffness associated with hypertonia. While medications
      are typically used to treat the general symptoms of spasticity, they often have additional
      side effects, like muscle weakness, that can impede rehabilitation. Physical therapeutics
      offer an alternative to these drug treatments, but the most effective therapeutic strategy
      for managing spasticity has not yet been identified. A combination of physical therapeutics
      may provide the best strategy for managing spasticity while also improving general motor
      control for functional movements.

      Walking ability can be improved through locomotor training, which has also been shown to
      reduce spasticity. When locomotor training is combined with electrical stimulation, the
      benefits of training may be increased. To investigate the potential benefits of this
      combinatorial treatment strategy, investigators will use a kind of electrical stimulation
      called transcutaneous spinal cord stimulation ("TSS") to stimulate spinal cord nerves during
      locomotor training.

      In order to facilitate the translation of study findings into clinical practice, this study
      uses a pragmatic design, meaning that the study will involve the use of real world clinical
      settings and practices. Participants will undergo their standard physical therapist directed
      locomotor training program while receiving transcutaneous spinal cord stimulation (TSS) as an
      additional treatment. The effects of locomotor training alone will be compared to the
      combination of locomotor training with TSS, specifically comparing the effects of these
      treatments on spasticity and walking function.

      Investigators expect that the combination of TSS with locomotor training will provide 1) a
      greater reduction in spasticity and 2) a greater improvement of walking function compared to
      locomotor training alone.

      The findings from this study have the potential to rapidly facilitate the translation of a
      novel combination treatment for the management of spasticity and improvement of walking
      function into real world clinical practice.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Outcomes Assessor)
measure: Change in Walking Function - 10m Walk Walking Speed (m/s)
time frame: Change in 10m Walk Speed (m/s) during the Intervention Phase (Week 2 test to Week 4 test)
description: You will walk over a mat that contains sensors to measure your walking speed as well as wear motion tracking sensors. You will be allowed to use whatever assistive devices you typically use (e.g., braces, walker, forearm crutches). In addition to walking speed, we will also assess your gait kinematics.
measure: Change in Spasticity - Pendulum Test
time frame: Pendulum angle (degrees) change during the Intervention Phase (Week 2 test to Week 4 test)
description: This test measures the amount of spasticity in your leg muscles. You will sit at the edge of a mat with your lower legs hanging over the edge of the mat. Motion capture sensors (Xsens) will be placed on both of your legs to record changes in your knee joint angles when your leg is dropped. The examiner will straighten your leg and then allow it to drop and swing over the edge of the mat. The angle of your knee and the movement of your leg will be recorded as it drops. This will be performed three times for each leg separately.
measure: Change in Walking Function - 2 Minute Walk
time frame: 2 Minute Walk test (distance) change during the Intervention Phase (Week 2 test to Week 4 test)
description: You will walk for 2 minutes overground and we will measure how far you walk.
measure: Change in Spasticity - Ankle Clonus Drop Test
time frame: Change in number of clonic ankle oscillations elicited via Ankle Clonus Drop Test during the Intervention Phase (Week 2 test to Week 4 test)
description: This test measures the amount of spasticity in your ankle. We will use the motion capture sensors to record your ankle joint angles. For this test you will sit upright. Your leg will be raised to 10cm above the rest position and released allowing the front of your foot to land on the edge of a box. The angle bouncing movement of your foot (clonus) will be recorded as it drops and catches on the box. This will be performed three times for each leg separately. Full details of test methods can be found at: Manella, Roach, and Field-Fote. Temporal Indices of Ankle Clonus and Relationship to Electrophysiologic and Clinical Measures in Persons With Spinal Cord Injury. J Neurol Phys Ther. 2017 Oct;41(4):229-238.
measure: Change in Spasticity - Muscle Co-contraction During Voluntary Activation
time frame: Co-contraction change during the Intervention Phase (Week 2 test to Week 4 test)
description: Muscle activity will be recorded using electromyography (EMG) during activities where you move your legs, and activities where your legs are moved by the examiner. Electrodes will be placed on four muscles of your legs (front and back of your thigh and lower leg), you will be asked to move your ankles and extend your legs while we record your muscle activity. We will test whether the EMG is activated in only one muscle (isolated) when you try to activate that muscle, or whether muscles that you are not trying to activate are also activated at the same time (co-contraction)
measure: Change in Spasticity - Spinal Cord Assessment Tool for Spastic Reflexes (SCATS) Test
time frame: SCATS scores change during the Intervention Phase (Week 2 test to Week 4 test)
description: A trained therapist will perform the SCATS assessment before and after each training session. SCATS assesses 3 aspects of spasticity: clonus, flexor spasms, extensor spasms in response to perturbation. Scores range from 0-3 as follows: 0 = no reaction; 1 = mild, <3 sec response; 2 = moderate, 3-10 sec response; 3 = severe, >10 sec response
measure: Stimulation Tolerability
time frame: Numerical rating scale of painfulness of stimulation in stimulation group only during stimulation weeks only (weeks 3 and 4)
description: Using a 0-10 numerical rating scale (NRS) for pain, you will be asked your perception of pain during the final 2 weeks of stimulation. NRS anchors are 0 = no pain, 10 = pain as bad as you can imagine
arm group label: Subthreshold
arm group type: Sham Comparator
description: Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will briefly ramp up to the lowest intensity that is first detected by the participant and then ramped down to a level no longer detected by the participant. Participants will continue their locomotor training.
arm group label: Active
arm group type: Experimental
description: Individuals will undergo their standard physical therapist directed locomotor training while receiving transcutaneous spinal cord stimulation. The stimulation intensity will ramp up slowly to a level that produces parasthesia (tingling) throughout the lower extremity. This intensity will be applied for 30 minutes while participants continue their locomotor training.
intervention type: Device
intervention name: Transcutaneous spinal stimulation
description: For TSS, a transcutaneous electrical nerve stimulation (TENS) unit is used. A 2 inch diameter round electrode is placed on the skin over T11/T12 (cathode), and a large butterfly electrode is placed on the skin over the umbilicus (anode). Pulse width is set to 400 microseconds at 50 Hz.
arm group label: Active
arm group label: Subthreshold
other name: TSS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Edelle C Field-Fote, PT, PhD
role: Principal Investigator
affiliation: Shepherd Center, Inc
facility: 
country: United States
responsible party type: Sponsor
mesh term: Muscle Spasticity
mesh term: Spinal Cord Injuries
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 