<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/NCT03237091</url>
  </required_header>
  <id_info>
    <org_study_id>723</org_study_id>
    <nct_id>NCT03237091</nct_id>
  </id_info>
  <brief_title>Enhancing Corticospinal Excitability to Improve Functional Recovery</brief_title>
  <official_title>Enhancing Corticospinal Excitability to Improve Functional Recovery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Shepherd Center, Atlanta GA</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>The Craig H. Neilsen Foundation</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Shepherd Center, Atlanta GA</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>
      Research indicates that increasing brain excitability might help improve hand function in&#xD;
      people with spinal cord injury. Brain stimulation that uses electrodes placed on the surface&#xD;
      of the scalp (also called &quot;non-invasive brain stimulation&quot;) increases brain excitability and&#xD;
      has the potential to make it easier for the brain and nervous system to respond to arm and&#xD;
      hand training. The purpose of this study is to compare four different types of stimulation&#xD;
      for increasing brain excitability to determine which types are best for helping people with&#xD;
      tetraplegia improve their ability to use their arms and hands. To fully evaluate the value of&#xD;
      brain stimulation on arm and hand function, the investigators will also evaluate the effect&#xD;
      of sham (fake) stimulation. Each participant will receive a single session of each of the&#xD;
      five types of stimulation being tested.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Restoration of upper extremity function is often the top rehabilitation goal for persons who&#xD;
      have sustained a cervical spinal cord injury (SCI). Following SCI, beyond the disruption&#xD;
      caused by the injury itself, maladaptive cortical reorganization further limits descending&#xD;
      corticospinal drive. Therefore, therapies aimed at increasing the descending drive provided&#xD;
      by corticospinal and other descending supraspinal tracts could be beneficial adjuncts to&#xD;
      commonly used rehabilitation therapies. While many rehabilitation research strategies for&#xD;
      improving function following SCI target the spinal circuitry, relatively few rehabilitative&#xD;
      approaches are directed toward promoting supraspinal neuroplasticity to reduce impairment by&#xD;
      increasing volitional control. Spectacular high-tech interventions and elegant high-tech&#xD;
      outcome measures generate a great deal of excitement in the scientific world. However, the&#xD;
      technological investment and training required for these approaches and the questionable&#xD;
      clinical meaningfulness of the outcomes is a major limitation to their real-world value.&#xD;
&#xD;
      Transcranial direct current stimulation (tDCS) is a clinically accessible form of&#xD;
      non-invasive brain stimulation (NIBS) that has been shown to improve upper extremity function&#xD;
      in persons with SCI. Clinical accessibility and the potential for prolonged modulation of&#xD;
      cortical excitability make tDCS is an attractive tool for non-invasive modulation of&#xD;
      corticospinal excitability.&#xD;
&#xD;
      Beyond traditional tDCS, intriguing recent studies in non-disabled individuals suggest a&#xD;
      novel form of NIBS, transcranial pulsed current stimulation (tPCS), may be more effective for&#xD;
      inducing changes in corticospinal excitability. tPCS utilizes unidirectional, positive pulses&#xD;
      of current separated by brief interpulse intervals rather than continuous direct current.&#xD;
      Some evidence from our lab and others indicates that patterned stimulation has a larger&#xD;
      influence on neural excitability than uniform stimulation.&#xD;
&#xD;
      Importantly, the efficacy of NIBS is dependent upon stimulation site. Since persons with&#xD;
      tetraplegia have bimanual impairments, it has been suggested that bihemispheric anodal&#xD;
      (excitatory) tDCS may be of value. Bihemispheric anodal tDCS has been studied in non-disabled&#xD;
      individuals; this approach was found to be safe and was associated with improved bimanual&#xD;
      control. However, the value of this approach has not previously been assessed in persons with&#xD;
      tetraplegia.&#xD;
&#xD;
      The investigators propose a randomized, sham-controlled crossover study in which two forms of&#xD;
      NIBS (tDCS and tPCS) will be compared with a sham-control intervention to determine their&#xD;
      relative efficacy for improving upper extremity strength and motor control (Aim 1) and&#xD;
      corticospinal excitability (Aim 2) in individuals with chronic (≥ 6 months) tetraplegia. The&#xD;
      efficacy of two different stimulation montages, uni- and bihemispheric, will also be compared&#xD;
      (Aim 3). Subjects will receive a single session of each NIBS condition (unihemispheric tDCS,&#xD;
      bihemispheric tDCS, unihemispheric tPCS, bihemispheric tPCS) and a sham-control condition.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">May 3, 2018</start_date>
  <completion_date type="Actual">September 27, 2019</completion_date>
  <primary_completion_date type="Actual">September 27, 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>Crossover Assignment</intervention_model>
    <intervention_model_description>This is a a randomized, sham-controlled crossover study in which all participants will participate in a single session of each type of intervention.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from Baseline Motor Control &amp; Strength</measure>
    <time_frame>Through study completion, up to 5 weeks</time_frame>
    <description>The motor control outcome measure evaluates how quickly the participant can move their fingers. Participants will tap their thumb or index finger as fast as possible for 10 seconds at a time while a sensor counts the number of taps. The strength outcome measure evaluates the participant's hand strength. Participants will use their thumb and index finger to pinch a hand-held device that measures their strength.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline Corticospinal Excitability</measure>
    <time_frame>Through study completion, up to 5 weeks</time_frame>
    <description>This outcome measure evaluates communication between the participant's brain and spinal cord. The skin over the muscles of both arms and hands will be cleaned with an alcohol swab and a mildly abrasive paste (similar to the feel of toothpaste). Sensors that detect muscle activity will be placed over these sites. Pulses of stimulation will be applied to the participant's head using a type of non-invasive brain stimulation called transcranial magnetic stimulation (TMS). This stimulation will activate the brain regions that control arm and hand movement. The strength of the stimulation will be increased until it causes the muscles of the arm and hand to twitch, and the size of the muscle response will be recorded with the sensors placed over the muscles.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Stimulation Questionnaire</measure>
    <time_frame>Through study completion, up to 5 weeks</time_frame>
    <description>This outcome measure evaluates the participant's perception of stimulation.</description>
  </secondary_outcome>
  <number_of_arms>5</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Spinal Cord Injuries</condition>
  <condition>Tetraplegia</condition>
  <arm_group>
    <arm_group_label>bihemispheric transcranial pulsed current stimulation (tPCS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>unihemispheric transcranial pulsed current stimulation (tPCS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>bihemispheric transcranial direct current stimulation (tDCS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>unihemispheric transcranial direct current stimulation (tDCS)</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <arm_group>
    <arm_group_label>sham-control</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>bihemispheric transcranial pulsed current stimulation (tPCS)</intervention_name>
    <description>Two sets of sponge electrodes (one set placed on each side of the head) will be placed on the participant's head. The transcranial electrical stimulator will apply unidirectional, positive pulses of current separated by brief interpulse intervals to the scalp via the sponges for 30 minutes.</description>
    <arm_group_label>bihemispheric transcranial pulsed current stimulation (tPCS)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>unihemispheric transcranial pulsed current stimulation (tPCS)</intervention_name>
    <description>One set of sponge electrodes will be placed on the participant's head. The transcranial electrical stimulator will apply unidirectional, positive pulses of current separated by brief interpulse intervals to the scalp via the sponges for 30 minutes.</description>
    <arm_group_label>unihemispheric transcranial pulsed current stimulation (tPCS)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>bihemispheric transcranial direct current stimulation (tDCS)</intervention_name>
    <description>Two sets of sponge electrodes (one set placed on each side of the head) will be placed on the participant's head. The transcranial electrical stimulator will apply continuous, direct current to the scalp via the sponges for 30 minutes.</description>
    <arm_group_label>bihemispheric transcranial direct current stimulation (tDCS)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>unihemispheric transcranial direct current stimulation (tDCS)</intervention_name>
    <description>One set of sponge electrodes will be placed on the participant's head. The transcranial electrical stimulator will apply continuous, direct current to the scalp via the sponges for 30 minutes.</description>
    <arm_group_label>unihemispheric transcranial direct current stimulation (tDCS)</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>sham-control</intervention_name>
    <description>Sponge electrodes will be placed on the participant's head. The transcranial electrical stimulator will apply stimulation to the scalp via the sponges for 1-2 minutes. The stimulator will then be turned off.</description>
    <arm_group_label>sham-control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Cervical (neurological level C1-C8) SCI occurring more than 6 months ago&#xD;
&#xD;
          -  Any severity classification (ASIA/ISNCSCI A, B, C, D)&#xD;
&#xD;
          -  Self-reported functional limitation in at least one upper limb&#xD;
&#xD;
          -  Ability to voluntarily move thumb or index finger (visible twitch) of both upper limbs&#xD;
&#xD;
          -  Ability and willingness to consent to participate in the study and authorize use of&#xD;
             protected health information&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pacemaker or metal implant in the head&#xD;
&#xD;
          -  History of seizure&#xD;
&#xD;
          -  History of frequent or severe headaches&#xD;
&#xD;
          -  Damage to the nerves of the arms/hands (lower motor neuron damage) as documented in&#xD;
             medical record, per participant report, or during in-person screening&#xD;
&#xD;
          -  Prior tendon or nerve transfer surgery&#xD;
&#xD;
          -  Severe pain or hypersensitivity of the arm/hand that would limit participation in arm&#xD;
             and hand training&#xD;
&#xD;
          -  Severe contractures of the arm/hand that would limit participation in arm and hand&#xD;
             training&#xD;
&#xD;
          -  Current pregnancy&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Shepherd Center</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>October 2019</verification_date>
  <study_first_submitted>July 24, 2017</study_first_submitted>
  <study_first_submitted_qc>August 1, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">August 2, 2017</study_first_posted>
  <last_update_submitted>October 7, 2019</last_update_submitted>
  <last_update_submitted_qc>October 7, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 8, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>non-invasive brain stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Cord Injuries</mesh_term>
    <mesh_term>Quadriplegia</mesh_term>
  </condition_browse>
  <!-- Results have not yet been posted for this study                                          -->
</clinical_study>


download date: ClinicalTrials.gov processed this data on September 20, 2023
link text: Link to the current ClinicalTrials.gov record.
url: https://clinicaltrials.gov/ct2/show/NCT03237091
org study id: 723
nct id: NCT03237091
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Research indicates that increasing brain excitability might help improve hand function in
      people with spinal cord injury. Brain stimulation that uses electrodes placed on the surface
      of the scalp (also called "non-invasive brain stimulation") increases brain excitability and
      has the potential to make it easier for the brain and nervous system to respond to arm and
      hand training. The purpose of this study is to compare four different types of stimulation
      for increasing brain excitability to determine which types are best for helping people with
      tetraplegia improve their ability to use their arms and hands. To fully evaluate the value of
      brain stimulation on arm and hand function, the investigators will also evaluate the effect
      of sham (fake) stimulation. Each participant will receive a single session of each of the
      five types of stimulation being tested.
Restoration of upper extremity function is often the top rehabilitation goal for persons who
      have sustained a cervical spinal cord injury (SCI). Following SCI, beyond the disruption
      caused by the injury itself, maladaptive cortical reorganization further limits descending
      corticospinal drive. Therefore, therapies aimed at increasing the descending drive provided
      by corticospinal and other descending supraspinal tracts could be beneficial adjuncts to
      commonly used rehabilitation therapies. While many rehabilitation research strategies for
      improving function following SCI target the spinal circuitry, relatively few rehabilitative
      approaches are directed toward promoting supraspinal neuroplasticity to reduce impairment by
      increasing volitional control. Spectacular high-tech interventions and elegant high-tech
      outcome measures generate a great deal of excitement in the scientific world. However, the
      technological investment and training required for these approaches and the questionable
      clinical meaningfulness of the outcomes is a major limitation to their real-world value.

      Transcranial direct current stimulation (tDCS) is a clinically accessible form of
      non-invasive brain stimulation (NIBS) that has been shown to improve upper extremity function
      in persons with SCI. Clinical accessibility and the potential for prolonged modulation of
      cortical excitability make tDCS is an attractive tool for non-invasive modulation of
      corticospinal excitability.

      Beyond traditional tDCS, intriguing recent studies in non-disabled individuals suggest a
      novel form of NIBS, transcranial pulsed current stimulation (tPCS), may be more effective for
      inducing changes in corticospinal excitability. tPCS utilizes unidirectional, positive pulses
      of current separated by brief interpulse intervals rather than continuous direct current.
      Some evidence from our lab and others indicates that patterned stimulation has a larger
      influence on neural excitability than uniform stimulation.

      Importantly, the efficacy of NIBS is dependent upon stimulation site. Since persons with
      tetraplegia have bimanual impairments, it has been suggested that bihemispheric anodal
      (excitatory) tDCS may be of value. Bihemispheric anodal tDCS has been studied in non-disabled
      individuals; this approach was found to be safe and was associated with improved bimanual
      control. However, the value of this approach has not previously been assessed in persons with
      tetraplegia.

      The investigators propose a randomized, sham-controlled crossover study in which two forms of
      NIBS (tDCS and tPCS) will be compared with a sham-control intervention to determine their
      relative efficacy for improving upper extremity strength and motor control (Aim 1) and
      corticospinal excitability (Aim 2) in individuals with chronic (≥ 6 months) tetraplegia. The
      efficacy of two different stimulation montages, uni- and bihemispheric, will also be compared
      (Aim 3). Subjects will receive a single session of each NIBS condition (unihemispheric tDCS,
      bihemispheric tDCS, unihemispheric tPCS, bihemispheric tPCS) and a sham-control condition.
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: This is a a randomized, sham-controlled crossover study in which all participants will participate in a single session of each type of intervention.
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Change from Baseline Motor Control & Strength
time frame: Through study completion, up to 5 weeks
description: The motor control outcome measure evaluates how quickly the participant can move their fingers. Participants will tap their thumb or index finger as fast as possible for 10 seconds at a time while a sensor counts the number of taps. The strength outcome measure evaluates the participant's hand strength. Participants will use their thumb and index finger to pinch a hand-held device that measures their strength.
measure: Change from Baseline Corticospinal Excitability
time frame: Through study completion, up to 5 weeks
description: This outcome measure evaluates communication between the participant's brain and spinal cord. The skin over the muscles of both arms and hands will be cleaned with an alcohol swab and a mildly abrasive paste (similar to the feel of toothpaste). Sensors that detect muscle activity will be placed over these sites. Pulses of stimulation will be applied to the participant's head using a type of non-invasive brain stimulation called transcranial magnetic stimulation (TMS). This stimulation will activate the brain regions that control arm and hand movement. The strength of the stimulation will be increased until it causes the muscles of the arm and hand to twitch, and the size of the muscle response will be recorded with the sensors placed over the muscles.
measure: Stimulation Questionnaire
time frame: Through study completion, up to 5 weeks
description: This outcome measure evaluates the participant's perception of stimulation.
arm group label: bihemispheric transcranial pulsed current stimulation (tPCS)
arm group type: Experimental
arm group label: unihemispheric transcranial pulsed current stimulation (tPCS)
arm group type: Experimental
arm group label: bihemispheric transcranial direct current stimulation (tDCS)
arm group type: Experimental
arm group label: unihemispheric transcranial direct current stimulation (tDCS)
arm group type: Experimental
arm group label: sham-control
arm group type: Active Comparator
intervention type: Other
intervention name: bihemispheric transcranial pulsed current stimulation (tPCS)
description: Two sets of sponge electrodes (one set placed on each side of the head) will be placed on the participant's head. The transcranial electrical stimulator will apply unidirectional, positive pulses of current separated by brief interpulse intervals to the scalp via the sponges for 30 minutes.
arm group label: bihemispheric transcranial pulsed current stimulation (tPCS)
intervention type: Other
intervention name: unihemispheric transcranial pulsed current stimulation (tPCS)
description: One set of sponge electrodes will be placed on the participant's head. The transcranial electrical stimulator will apply unidirectional, positive pulses of current separated by brief interpulse intervals to the scalp via the sponges for 30 minutes.
arm group label: unihemispheric transcranial pulsed current stimulation (tPCS)
intervention type: Other
intervention name: bihemispheric transcranial direct current stimulation (tDCS)
description: Two sets of sponge electrodes (one set placed on each side of the head) will be placed on the participant's head. The transcranial electrical stimulator will apply continuous, direct current to the scalp via the sponges for 30 minutes.
arm group label: bihemispheric transcranial direct current stimulation (tDCS)
intervention type: Other
intervention name: unihemispheric transcranial direct current stimulation (tDCS)
description: One set of sponge electrodes will be placed on the participant's head. The transcranial electrical stimulator will apply continuous, direct current to the scalp via the sponges for 30 minutes.
arm group label: unihemispheric transcranial direct current stimulation (tDCS)
intervention type: Other
intervention name: sham-control
description: Sponge electrodes will be placed on the participant's head. The transcranial electrical stimulator will apply stimulation to the scalp via the sponges for 1-2 minutes. The stimulator will then be turned off.
arm group label: sham-control
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
facility: 
country: United States
responsible party type: Sponsor
mesh term: Spinal Cord Injuries
mesh term: Quadriplegia