<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/NCT03815721</url>
  </required_header>
  <id_info>
    <org_study_id>2016-16</org_study_id>
    <nct_id>NCT03815721</nct_id>
  </id_info>
  <brief_title>Carry-over Effects of Repetitively Applied Transcutaneous Spinal Cord Stimulation on Spasticity</brief_title>
  <acronym>SCS-CorE</acronym>
  <official_title>Carry-over Effects of Repetitively Applied Transcutaneous Spinal Cord Stimulation on Spasticity and Residual Motor Control in Incomplete Spinal Cord Injured Individuals</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Swiss Paraplegic Centre Nottwil</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Medical University of Vienna</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Swiss Paraplegic Centre Nottwil</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Spinal cord injury is a devastating condition, causing substantial impairment of vital body&#xD;
      functions caudal to the lesion. A major cause of disability stems from spasticity, a common&#xD;
      secondary sequelae. Its various clinical manifestations include spasms, clonus, and&#xD;
      resistance to passive movements, and often present a major hindrance in rehabilitation,&#xD;
      further deteriorate residual motor performance, and negatively impact independence and&#xD;
      quality of life. Despite its high prevalence, successful management of spasticity has&#xD;
      remained difficult. Standard-of-care treatment modalities are often insufficient or bear the&#xD;
      risk of undesirable side effects further accentuating paresis. Epidural stimulation of the&#xD;
      lumbar spinal cord via implanted electrodes provides for an alternative approach. It works&#xD;
      through modifying the dysregulated neural signal processing of spared spinal circuitry caudal&#xD;
      to the injury. Its ameliorative effects on severe lower-limb spasticity have been&#xD;
      repetitively reported. Yet, epidural spinal cord stimulation in motor disorders is still&#xD;
      off-label, applied in relatively few patients only, also because of its invasive character,&#xD;
      the time consuming testing phase for its effective application, and the lack of markers to&#xD;
      identify responders in advance. With the development of transcutaneous spinal cord&#xD;
      stimulation, a method became available to activate the same input structures to the lumbar&#xD;
      spinal cord as with epidural stimulation and hence to induce similar neuromodulatory effects,&#xD;
      yet non-invasively, using standard equipment available at rehabilitation centers. A recent&#xD;
      proof-of-concept study has shown that a single 30-minute session of transcutaneous spinal&#xD;
      cord stimulation controlled various clinical signs of spasticity and augmented residual motor&#xD;
      control in spinal cord injured individuals for several hours beyond its application. Further,&#xD;
      in one subject, the stimulation was repetitively applied for six weeks, resulting in&#xD;
      cumulative therapeutic effects persisting for 10 days after its discontinuation. These&#xD;
      observations strongly suggest that the stimulation can induce beneficial neuroplastic&#xD;
      adaptations of spared spinal systems and their interaction with residual supraspinal control.&#xD;
      The proposed research aims at studying the reproducibility of these findings in a&#xD;
      statistically sound cohort of individuals with spinal cord injury and testing the&#xD;
      applicability and acceptance of transcutaneous spinal cord stimulation as a home-based&#xD;
      therapy.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Withdrawn</overall_status>
  <why_stopped>
    Decision of the 2 PI's&#xD;
  </why_stopped>
  <start_date type="Actual">January 7, 2019</start_date>
  <completion_date type="Anticipated">June 2024</completion_date>
  <primary_completion_date type="Anticipated">December 2023</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in spasticity index</measure>
    <time_frame>from day 1 to day 57</time_frame>
    <description>Spasticity index based on the Wartenberg pendulum test: For the pendulum test, subjects will be in a supported sitting position with the trunk reclined approximately 30°. The examiner will lift one leg to a horizontal position, release it, and let it oscillate passively until it stops. The pendulum test will be repeated three times on each side, separated by phases of relaxation. The spasticity index is calculated subtracting the knee angle of the initial horizontal leg position from the peak flexion angle of the first swing divided by the final knee resting angle. Scores ≥ 1 denote non-spastic conditions, and 0 extreme spasticity.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in numeric rating scale spasticity</measure>
    <time_frame>day 1, 8, 29, 50 and 57</time_frame>
    <description>The severity of spasticity is rated using a numeric rating scale from a minimum of 0 to a maximum of 10. Higher values represent worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Modified Ashworth Scale</measure>
    <time_frame>from day 1 to day 57</time_frame>
    <description>The resistance to passive movement will be clinically graded according to the Modified Ashworth Scale. Individual scores from both legs will be summed (with a value of 1.5 for the 1+ scoring category) to result in a single Modified Ashworth Scale-sum score (0-96; 0, no increase in muscle tone) per assessment. Higher values represent worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in adductor tone rating</measure>
    <time_frame>from day 1 to day 57</time_frame>
    <description>5-point ordinal scale describing adductor tone during passive abduction (0: normal tone - 4: maximal tone). Higher values represent worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Penn Spasm Frequency Scale</measure>
    <time_frame>from day 1 to day 57</time_frame>
    <description>5-point scale rating the frequency and severity of spasms (0: no spasms - 4: more than 10 spasms per hour). Higher values represent worse outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in resistance of the lower limbs</measure>
    <time_frame>from day 1 to day 57</time_frame>
    <description>Measure of the resistance of the lower limbs to manipulation performed by a robotic system (MotionMaker, SWORTEC SA). The MotionMaker measures torque (N) and power output (W).</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in 6-minute walk test</measure>
    <time_frame>from day 1 to day 57</time_frame>
    <description>distance in meters walked over a span of 6 minutes</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Walking Index for Spinal Cord Injury II Scale</measure>
    <time_frame>from day 1 to day 57</time_frame>
    <description>21-point ordinal scale that rates the extent and nature of assistance (e.g., walker, crutches, cane, braces, physical assistance) required to complete the 10-m walk test (0: unable to complete the test - 20: ambulated without any assistance). Higher values represent better outcome.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">0</enrollment>
  <condition>Spinal Cord Injuries</condition>
  <condition>Spasticity, Muscle</condition>
  <arm_group>
    <arm_group_label>daily stimulation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30-minute sessions of transcutaneous spinal cord stimulation using the Stimulette r2x+ will be repetitively applied 7 times per week.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>stimulation every other day</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>30-minute sessions of transcutaneous spinal cord stimulation using the Stimulette r2x+ will be repetitively applied 3 times per week.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Stimulette r2x+</intervention_name>
    <description>device for repetitive transcutaneous spinal cord stimulation</description>
    <arm_group_label>daily stimulation</arm_group_label>
    <arm_group_label>stimulation every other day</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  motor and sensory incomplete spinal cord injury classified as grade C or D on the&#xD;
             American Spinal Injury Association Impairment Scale&#xD;
&#xD;
          -  neurological level of spinal cord injury: third cervical to tenth thoracic segment&#xD;
&#xD;
          -  chronic condition (≥ 12 months post-spinal cord injury)&#xD;
&#xD;
          -  preserved segmental and cutaneo-muscular reflexes in the lower limbs&#xD;
&#xD;
          -  able to be verticalized for 6 minutes (with walking aids)&#xD;
&#xD;
          -  preserved joint mobility, no musculoskeletal diseases&#xD;
&#xD;
          -  spasticity (with/without antispasticity medication)&#xD;
&#xD;
          -  stable antispasmodic medication one month prior to as well as during study&#xD;
             participation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  neuromuscular diseases, e.g., amyotrophic lateral sclerosis (ALS), Parkinson's&#xD;
             disease, Guillain-Barré syndrome, muscular dystrophy&#xD;
&#xD;
          -  dermatological issues at the stimulation site&#xD;
&#xD;
          -  acute urinary tract infection at study entry&#xD;
&#xD;
          -  active implants (e.g., cardiac pacemaker, drug pump)&#xD;
&#xD;
          -  passive implants between the ninth thoracic level and the first lumbal level (e.g.&#xD;
             metal screws/plates for surgical stabilization of spinal fractures)&#xD;
&#xD;
          -  malignant diseases&#xD;
&#xD;
          -  heart insufficiency&#xD;
&#xD;
          -  potential pregnancy (pregnancy test to be conducted as part of the first evaluation)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Ursula Hofstötter</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University Vienna</affiliation>
  </overall_official>
  <overall_official>
    <last_name>Angela Frotzler</last_name>
    <role>Principal Investigator</role>
    <affiliation>Swiss Paraplegic Centre</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Swiss Paraplegic Centre</name>
      <address>
        <city>Nottwil</city>
        <state>LU</state>
        <zip>6207</zip>
        <country>Switzerland</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Switzerland</country>
  </location_countries>
  <verification_date>March 2023</verification_date>
  <study_first_submitted>January 22, 2019</study_first_submitted>
  <study_first_submitted_qc>January 23, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 24, 2019</study_first_posted>
  <last_update_submitted>March 14, 2023</last_update_submitted>
  <last_update_submitted_qc>March 14, 2023</last_update_submitted_qc>
  <last_update_posted type="Actual">March 16, 2023</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>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03815721
org study id: 2016-16
nct id: NCT03815721
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Spinal cord injury is a devastating condition, causing substantial impairment of vital body
      functions caudal to the lesion. A major cause of disability stems from spasticity, a common
      secondary sequelae. Its various clinical manifestations include spasms, clonus, and
      resistance to passive movements, and often present a major hindrance in rehabilitation,
      further deteriorate residual motor performance, and negatively impact independence and
      quality of life. Despite its high prevalence, successful management of spasticity has
      remained difficult. Standard-of-care treatment modalities are often insufficient or bear the
      risk of undesirable side effects further accentuating paresis. Epidural stimulation of the
      lumbar spinal cord via implanted electrodes provides for an alternative approach. It works
      through modifying the dysregulated neural signal processing of spared spinal circuitry caudal
      to the injury. Its ameliorative effects on severe lower-limb spasticity have been
      repetitively reported. Yet, epidural spinal cord stimulation in motor disorders is still
      off-label, applied in relatively few patients only, also because of its invasive character,
      the time consuming testing phase for its effective application, and the lack of markers to
      identify responders in advance. With the development of transcutaneous spinal cord
      stimulation, a method became available to activate the same input structures to the lumbar
      spinal cord as with epidural stimulation and hence to induce similar neuromodulatory effects,
      yet non-invasively, using standard equipment available at rehabilitation centers. A recent
      proof-of-concept study has shown that a single 30-minute session of transcutaneous spinal
      cord stimulation controlled various clinical signs of spasticity and augmented residual motor
      control in spinal cord injured individuals for several hours beyond its application. Further,
      in one subject, the stimulation was repetitively applied for six weeks, resulting in
      cumulative therapeutic effects persisting for 10 days after its discontinuation. These
      observations strongly suggest that the stimulation can induce beneficial neuroplastic
      adaptations of spared spinal systems and their interaction with residual supraspinal control.
      The proposed research aims at studying the reproducibility of these findings in a
      statistically sound cohort of individuals with spinal cord injury and testing the
      applicability and acceptance of transcutaneous spinal cord stimulation as a home-based
      therapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
measure: Change in spasticity index
time frame: from day 1 to day 57
description: Spasticity index based on the Wartenberg pendulum test: For the pendulum test, subjects will be in a supported sitting position with the trunk reclined approximately 30°. The examiner will lift one leg to a horizontal position, release it, and let it oscillate passively until it stops. The pendulum test will be repeated three times on each side, separated by phases of relaxation. The spasticity index is calculated subtracting the knee angle of the initial horizontal leg position from the peak flexion angle of the first swing divided by the final knee resting angle. Scores ≥ 1 denote non-spastic conditions, and 0 extreme spasticity.
measure: Change in numeric rating scale spasticity
time frame: day 1, 8, 29, 50 and 57
description: The severity of spasticity is rated using a numeric rating scale from a minimum of 0 to a maximum of 10. Higher values represent worse outcome.
measure: Change in Modified Ashworth Scale
time frame: from day 1 to day 57
description: The resistance to passive movement will be clinically graded according to the Modified Ashworth Scale. Individual scores from both legs will be summed (with a value of 1.5 for the 1+ scoring category) to result in a single Modified Ashworth Scale-sum score (0-96; 0, no increase in muscle tone) per assessment. Higher values represent worse outcome.
measure: Change in adductor tone rating
time frame: from day 1 to day 57
description: 5-point ordinal scale describing adductor tone during passive abduction (0: normal tone - 4: maximal tone). Higher values represent worse outcome.
measure: Change in Penn Spasm Frequency Scale
time frame: from day 1 to day 57
description: 5-point scale rating the frequency and severity of spasms (0: no spasms - 4: more than 10 spasms per hour). Higher values represent worse outcome.
measure: Change in resistance of the lower limbs
time frame: from day 1 to day 57
description: Measure of the resistance of the lower limbs to manipulation performed by a robotic system (MotionMaker, SWORTEC SA). The MotionMaker measures torque (N) and power output (W).
measure: Change in 6-minute walk test
time frame: from day 1 to day 57
description: distance in meters walked over a span of 6 minutes
measure: Change in Walking Index for Spinal Cord Injury II Scale
time frame: from day 1 to day 57
description: 21-point ordinal scale that rates the extent and nature of assistance (e.g., walker, crutches, cane, braces, physical assistance) required to complete the 10-m walk test (0: unable to complete the test - 20: ambulated without any assistance). Higher values represent better outcome.
arm group label: daily stimulation
arm group type: Experimental
description: 30-minute sessions of transcutaneous spinal cord stimulation using the Stimulette r2x+ will be repetitively applied 7 times per week.
arm group label: stimulation every other day
arm group type: Experimental
description: 30-minute sessions of transcutaneous spinal cord stimulation using the Stimulette r2x+ will be repetitively applied 3 times per week.
intervention type: Device
intervention name: Stimulette r2x+
description: device for repetitive transcutaneous spinal cord stimulation
arm group label: daily stimulation
arm group label: stimulation every other day
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Ursula Hofstötter
role: Principal Investigator
affiliation: Medical University Vienna
last name: Angela Frotzler
role: Principal Investigator
affiliation: Swiss Paraplegic Centre
facility: 
country: Switzerland
responsible party type: Sponsor
mesh term: Muscle Spasticity
mesh term: Spinal Cord Injuries
sharing ipd: No