<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/NCT03833518</url>
  </required_header>
  <id_info>
    <org_study_id>Pro00002855</org_study_id>
    <nct_id>NCT03833518</nct_id>
  </id_info>
  <brief_title>Cortical Biomarkers of Hand Function and Recovery After Injury</brief_title>
  <official_title>Cortical Biomarkers of Hand Function and Recovery After Injury</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>VA Pittsburgh Healthcare System</agency>
      <agency_class>U.S. Fed</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>University of Pittsburgh</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>VA Pittsburgh Healthcare System</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>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot study to collect data to support a VA grant submission to study fMRI and&#xD;
      neurophysiological predictors of hand function and recovery during a robotic intervention in&#xD;
      people with hand impairments due to stroke or spinal cord injury.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      The loss of arm and hand function after cervical spinal cord injury (SCI) limits independence&#xD;
      and increases the cost of care. As a result, Veterans with tetraplegia prioritize restoration&#xD;
      of hand and arm function over all other rehabilitation goals. Similar to SCI, stroke of&#xD;
      supraspinal areas involved in motor control results in acute movement deficits in more than&#xD;
      85% of survivors. Despite advances in treatment and rehabilitation, 50% of stroke survivors&#xD;
      have persistent hand impairment. The loss of hand function and dexterity limits the ability&#xD;
      to perform many activities of daily living, and thus limits independence. Since motor&#xD;
      deficits are often permanent after SCI and stroke, new strategies are needed to restore&#xD;
      dexterous hand function.&#xD;
&#xD;
      Advances in functional imaging have enabled the measurement of finger-related activation&#xD;
      patterns in somatosensory cortex, but little is known about how these representational&#xD;
      patterns are impacted when hand function is lost. Prior studies of gross movements have&#xD;
      reported reorganization of cortical activity after injury. The investigators aim to improve&#xD;
      dexterous hand function by increasing our understanding of finger-related cortical&#xD;
      reorganization after lesions to the spinal or supraspinal structures. This understanding&#xD;
      could allow discrimination between adaptive and maladaptive patterns underlying hand function&#xD;
      and guide restorative therapies. Additionally, imaging biomarkers of injury often track with&#xD;
      functional recovery.&#xD;
&#xD;
      The aim is to improve dexterous hand function by increasing our understanding of&#xD;
      finger-related cortical reorganization after lesions to the spinal or supraspinal structures.&#xD;
      This understanding could allow discrimination between adaptive and maladaptive patterns&#xD;
      underlying hand function and guide restorative therapies. Additionally, imaging biomarkers of&#xD;
      injury often track with functional recovery.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Terminated</overall_status>
  <why_stopped>
    We only enrolled one participant, and this participant was withdrawn prior to collecting any&#xD;
    useful data. Then, COVID. Now, Dr. Collinger's faculty tenure with the VA ended.&#xD;
  </why_stopped>
  <start_date type="Actual">September 1, 2019</start_date>
  <completion_date type="Actual">October 15, 2020</completion_date>
  <primary_completion_date type="Actual">August 15, 2020</primary_completion_date>
  <phase>N/A</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <intervention_model_description>This is a pilot study to collect data to support a VA grant submission to study fMRI and neurophysiological predictors of hand function and recovery during a robotic intervention in people with hand impairments due to stroke or spinal cord injury.</intervention_model_description>
    <primary_purpose>Basic Science</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants that show significant finger-specific activation prior to the intervention</measure>
    <time_frame>Baseline, prior to intervention, week 1</time_frame>
    <description>The investigators will use functional magnetic resonance imaging (fMRI) to measure cortical activity relating to finger-specific brain activation before the rehabilitation intervention.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from baseline finger strength after rehabilitation intervention</measure>
    <time_frame>After intervention, 12 weeks</time_frame>
    <description>The investigators will assess finger strength of participants both before and after the rehabilitation intervention. The change in in finger strength will serve as a secondary outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from baseline in finger dexterity after rehabilitation intervention</measure>
    <time_frame>After intervention, 12 weeks</time_frame>
    <description>The investigators will assess each participant's ability to isolate movement of individual fingers both before and after the rehabilitation intervention. The change in this measure of dexterity will serve as a secondary outcome measure.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">1</enrollment>
  <condition>Stroke</condition>
  <condition>Spinal Cord Injuries</condition>
  <arm_group>
    <arm_group_label>Hand impairment due to stroke or spinal cord injury</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Individuals who have experienced a sub-cortical stroke or a cervical spinal cord injury resulting in loss of hand function.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Rehabilitation using motorized glove for stroke and spinal cord injury</intervention_name>
    <description>Individuals with hand impairment due to stroke or spinal cord injury will wear a motorized glove (Gloreha Sinfonia), or exoskeleton, as part of a rehabilitation protocol to improve dexterity. For each exercise, participants will attempt to do the action, receiving assistance as necessary via powered motors that can move each finger through its passive range of motion based on the current and target position.</description>
    <arm_group_label>Hand impairment due to stroke or spinal cord injury</arm_group_label>
    <other_name>Exoskeleton therapy</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Functional MRI for stroke and spinal cord injury</intervention_name>
    <description>All participants will undergo 3 functional MRI's (fMRI's), two at the beginning of the experiment to document brain activity related to movement intention and ability to sense movement. A third MRI will be performed after the rehabilitation is completed to document the change in brain activity related to movement intention and ability to sense movement.</description>
    <arm_group_label>Hand impairment due to stroke or spinal cord injury</arm_group_label>
    <other_name>fMRI</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Transcranial magnetic stimulation (TMS) for stroke and spinal cord injury</intervention_name>
    <description>Stimulation of the nervous system may be performed using a magnetic stimulator. TMS of the central nervous system is optional. Whether or not a participant undergoes TMS will depend upon their consent, their eligibility for TMS (i.e. no seizure history), and their neurological response to TMS.</description>
    <arm_group_label>Hand impairment due to stroke or spinal cord injury</arm_group_label>
    <other_name>TMS</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Normal or corrected to normal vision&#xD;
&#xD;
          -  Hand impairment due to spinal cord injury or stroke&#xD;
&#xD;
          -  Weakness of fingers&#xD;
&#xD;
          -  One year after stroke or spinal cord injury&#xD;
&#xD;
          -  Some proprioception (can feel when finger is moved, without seeing)&#xD;
&#xD;
          -  Minimal spasticity&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Implanted metal with is unsafe for MRI&#xD;
&#xD;
          -  Pregnant or expecting to become pregnant&#xD;
&#xD;
          -  History of hand surgery which is under evaluation&#xD;
&#xD;
          -  Cognitive or language issues that would interfere with following directions&#xD;
&#xD;
          -  Other neurological disorder that would affect movement&#xD;
&#xD;
          -  History of seizure or epilepsy&#xD;
&#xD;
          -  Body weight &gt; 300 pounds&#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>Jennifer Collinger, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>US Department of Veterans Affairs</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Pittsburgh</name>
      <address>
        <city>Pittsburgh</city>
        <state>Pennsylvania</state>
        <zip>15213</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Rathore SS, Hinn AR, Cooper LS, Tyroler HA, Rosamond WD. Characterization of incident stroke signs and symptoms: findings from the atherosclerosis risk in communities study. Stroke. 2002 Nov;33(11):2718-21. doi: 10.1161/01.str.0000035286.87503.31.</citation>
    <PMID>12411667</PMID>
  </reference>
  <reference>
    <citation>Peckham PH, Keith MW, Kilgore KL, Grill JH, Wuolle KS, Thrope GB, Gorman P, Hobby J, Mulcahey MJ, Carroll S, Hentz VR, Wiegner A; Implantable Neuroprosthesis Research Group. Efficacy of an implanted neuroprosthesis for restoring hand grasp in tetraplegia: a multicenter study. Arch Phys Med Rehabil. 2001 Oct;82(10):1380-8. doi: 10.1053/apmr.2001.25910.</citation>
    <PMID>11588741</PMID>
  </reference>
  <reference>
    <citation>Anderson KD. Targeting recovery: priorities of the spinal cord-injured population. J Neurotrauma. 2004 Oct;21(10):1371-83. doi: 10.1089/neu.2004.21.1371.</citation>
    <PMID>15672628</PMID>
  </reference>
  <reference>
    <citation>Doll U, Maurer-Burkhard B, Spahn B, Fromm B. Functional hand development in tetraplegia. Spinal Cord. 1998 Dec;36(12):818-21. doi: 10.1038/sj.sc.3100706.</citation>
    <PMID>9881729</PMID>
  </reference>
  <reference>
    <citation>Fawcett JW. Recovery from spinal cord injury: regeneration, plasticity and rehabilitation. Brain. 2009 Jun;132(Pt 6):1417-8. doi: 10.1093/brain/awp121. Epub 2009 May 8. No abstract available.</citation>
    <PMID>19429905</PMID>
  </reference>
  <reference>
    <citation>Nowak DA. The impact of stroke on the performance of grasping: usefulness of kinetic and kinematic motion analysis. Neurosci Biobehav Rev. 2008 Oct;32(8):1439-50. doi: 10.1016/j.neubiorev.2008.05.021. Epub 2008 May 23.</citation>
    <PMID>18582943</PMID>
  </reference>
  <reference>
    <citation>Raghavan P, Petra E, Krakauer JW, Gordon AM. Patterns of impairment in digit independence after subcortical stroke. J Neurophysiol. 2006 Jan;95(1):369-78. doi: 10.1152/jn.00873.2005. Epub 2005 Oct 5.</citation>
    <PMID>16207778</PMID>
  </reference>
  <reference>
    <citation>Lang CE, Schieber MH. Differential impairment of individuated finger movements in humans after damage to the motor cortex or the corticospinal tract. J Neurophysiol. 2003 Aug;90(2):1160-70. doi: 10.1152/jn.00130.2003. Epub 2003 Mar 26.</citation>
    <PMID>12660350</PMID>
  </reference>
  <reference>
    <citation>Lang CE, Schieber MH. Reduced muscle selectivity during individuated finger movements in humans after damage to the motor cortex or corticospinal tract. J Neurophysiol. 2004 Apr;91(4):1722-33. doi: 10.1152/jn.00805.2003. Epub 2003 Dec 10.</citation>
    <PMID>14668295</PMID>
  </reference>
  <reference>
    <citation>Wenzelburger R, Kopper F, Frenzel A, Stolze H, Klebe S, Brossmann A, Kuhtz-Buschbeck J, Golge M, Illert M, Deuschl G. Hand coordination following capsular stroke. Brain. 2005 Jan;128(Pt 1):64-74. doi: 10.1093/brain/awh317. Epub 2004 Oct 7.</citation>
    <PMID>15471902</PMID>
  </reference>
  <verification_date>April 2021</verification_date>
  <study_first_submitted>February 4, 2019</study_first_submitted>
  <study_first_submitted_qc>February 6, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 7, 2019</study_first_posted>
  <last_update_submitted>April 30, 2021</last_update_submitted>
  <last_update_submitted_qc>April 30, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 6, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>VA Pittsburgh Healthcare System</investigator_affiliation>
    <investigator_full_name>Jennifer Collinger</investigator_full_name>
    <investigator_title>Research Biomedical Engineer</investigator_title>
  </responsible_party>
  <keyword>hand</keyword>
  <keyword>rehabilitation</keyword>
  <keyword>motor cortex</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Spinal Cord Injuries</mesh_term>
    <mesh_term>Wounds and Injuries</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
    <ipd_description>Research information will not be shared with anyone outside of the research team.</ipd_description>
  </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/NCT03833518
org study id: Pro00002855
nct id: NCT03833518
lead sponsor: 
collaborator: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
This is a pilot study to collect data to support a VA grant submission to study fMRI and
      neurophysiological predictors of hand function and recovery during a robotic intervention in
      people with hand impairments due to stroke or spinal cord injury.
The loss of arm and hand function after cervical spinal cord injury (SCI) limits independence
      and increases the cost of care. As a result, Veterans with tetraplegia prioritize restoration
      of hand and arm function over all other rehabilitation goals. Similar to SCI, stroke of
      supraspinal areas involved in motor control results in acute movement deficits in more than
      85% of survivors. Despite advances in treatment and rehabilitation, 50% of stroke survivors
      have persistent hand impairment. The loss of hand function and dexterity limits the ability
      to perform many activities of daily living, and thus limits independence. Since motor
      deficits are often permanent after SCI and stroke, new strategies are needed to restore
      dexterous hand function.

      Advances in functional imaging have enabled the measurement of finger-related activation
      patterns in somatosensory cortex, but little is known about how these representational
      patterns are impacted when hand function is lost. Prior studies of gross movements have
      reported reorganization of cortical activity after injury. The investigators aim to improve
      dexterous hand function by increasing our understanding of finger-related cortical
      reorganization after lesions to the spinal or supraspinal structures. This understanding
      could allow discrimination between adaptive and maladaptive patterns underlying hand function
      and guide restorative therapies. Additionally, imaging biomarkers of injury often track with
      functional recovery.

      The aim is to improve dexterous hand function by increasing our understanding of
      finger-related cortical reorganization after lesions to the spinal or supraspinal structures.
      This understanding could allow discrimination between adaptive and maladaptive patterns
      underlying hand function and guide restorative therapies. Additionally, imaging biomarkers of
      injury often track with functional recovery.
allocation: N/A
intervention model: Single Group Assignment
intervention model description: This is a pilot study to collect data to support a VA grant submission to study fMRI and neurophysiological predictors of hand function and recovery during a robotic intervention in people with hand impairments due to stroke or spinal cord injury.
primary purpose: Basic Science
masking: None (Open Label)
measure: Number of participants that show significant finger-specific activation prior to the intervention
time frame: Baseline, prior to intervention, week 1
description: The investigators will use functional magnetic resonance imaging (fMRI) to measure cortical activity relating to finger-specific brain activation before the rehabilitation intervention.
measure: Change from baseline finger strength after rehabilitation intervention
time frame: After intervention, 12 weeks
description: The investigators will assess finger strength of participants both before and after the rehabilitation intervention. The change in in finger strength will serve as a secondary outcome measure.
measure: Change from baseline in finger dexterity after rehabilitation intervention
time frame: After intervention, 12 weeks
description: The investigators will assess each participant's ability to isolate movement of individual fingers both before and after the rehabilitation intervention. The change in this measure of dexterity will serve as a secondary outcome measure.
arm group label: Hand impairment due to stroke or spinal cord injury
arm group type: Experimental
description: Individuals who have experienced a sub-cortical stroke or a cervical spinal cord injury resulting in loss of hand function.
intervention type: Other
intervention name: Rehabilitation using motorized glove for stroke and spinal cord injury
description: Individuals with hand impairment due to stroke or spinal cord injury will wear a motorized glove (Gloreha Sinfonia), or exoskeleton, as part of a rehabilitation protocol to improve dexterity. For each exercise, participants will attempt to do the action, receiving assistance as necessary via powered motors that can move each finger through its passive range of motion based on the current and target position.
arm group label: Hand impairment due to stroke or spinal cord injury
other name: Exoskeleton therapy
intervention type: Other
intervention name: Functional MRI for stroke and spinal cord injury
description: All participants will undergo 3 functional MRI's (fMRI's), two at the beginning of the experiment to document brain activity related to movement intention and ability to sense movement. A third MRI will be performed after the rehabilitation is completed to document the change in brain activity related to movement intention and ability to sense movement.
arm group label: Hand impairment due to stroke or spinal cord injury
other name: fMRI
intervention type: Other
intervention name: Transcranial magnetic stimulation (TMS) for stroke and spinal cord injury
description: Stimulation of the nervous system may be performed using a magnetic stimulator. TMS of the central nervous system is optional. Whether or not a participant undergoes TMS will depend upon their consent, their eligibility for TMS (i.e. no seizure history), and their neurological response to TMS.
arm group label: Hand impairment due to stroke or spinal cord injury
other name: TMS
criteria: 
gender: All
minimum age: 18 Years
maximum age: 65 Years
healthy volunteers: No
last name: Jennifer Collinger, PhD
role: Principal Investigator
affiliation: US Department of Veterans Affairs
facility: 
country: United States
citation: Rathore SS, Hinn AR, Cooper LS, Tyroler HA, Rosamond WD. Characterization of incident stroke signs and symptoms: findings from the atherosclerosis risk in communities study. Stroke. 2002 Nov;33(11):2718-21. doi: 10.1161/01.str.0000035286.87503.31.
PMID: 12411667
citation: Peckham PH, Keith MW, Kilgore KL, Grill JH, Wuolle KS, Thrope GB, Gorman P, Hobby J, Mulcahey MJ, Carroll S, Hentz VR, Wiegner A; Implantable Neuroprosthesis Research Group. Efficacy of an implanted neuroprosthesis for restoring hand grasp in tetraplegia: a multicenter study. Arch Phys Med Rehabil. 2001 Oct;82(10):1380-8. doi: 10.1053/apmr.2001.25910.
PMID: 11588741
citation: Anderson KD. Targeting recovery: priorities of the spinal cord-injured population. J Neurotrauma. 2004 Oct;21(10):1371-83. doi: 10.1089/neu.2004.21.1371.
PMID: 15672628
citation: Doll U, Maurer-Burkhard B, Spahn B, Fromm B. Functional hand development in tetraplegia. Spinal Cord. 1998 Dec;36(12):818-21. doi: 10.1038/sj.sc.3100706.
PMID: 9881729
citation: Fawcett JW. Recovery from spinal cord injury: regeneration, plasticity and rehabilitation. Brain. 2009 Jun;132(Pt 6):1417-8. doi: 10.1093/brain/awp121. Epub 2009 May 8. No abstract available.
PMID: 19429905
citation: Nowak DA. The impact of stroke on the performance of grasping: usefulness of kinetic and kinematic motion analysis. Neurosci Biobehav Rev. 2008 Oct;32(8):1439-50. doi: 10.1016/j.neubiorev.2008.05.021. Epub 2008 May 23.
PMID: 18582943
citation: Raghavan P, Petra E, Krakauer JW, Gordon AM. Patterns of impairment in digit independence after subcortical stroke. J Neurophysiol. 2006 Jan;95(1):369-78. doi: 10.1152/jn.00873.2005. Epub 2005 Oct 5.
PMID: 16207778
citation: Lang CE, Schieber MH. Differential impairment of individuated finger movements in humans after damage to the motor cortex or the corticospinal tract. J Neurophysiol. 2003 Aug;90(2):1160-70. doi: 10.1152/jn.00130.2003. Epub 2003 Mar 26.
PMID: 12660350
citation: Lang CE, Schieber MH. Reduced muscle selectivity during individuated finger movements in humans after damage to the motor cortex or corticospinal tract. J Neurophysiol. 2004 Apr;91(4):1722-33. doi: 10.1152/jn.00805.2003. Epub 2003 Dec 10.
PMID: 14668295
citation: Wenzelburger R, Kopper F, Frenzel A, Stolze H, Klebe S, Brossmann A, Kuhtz-Buschbeck J, Golge M, Illert M, Deuschl G. Hand coordination following capsular stroke. Brain. 2005 Jan;128(Pt 1):64-74. doi: 10.1093/brain/awh317. Epub 2004 Oct 7.
PMID: 15471902
responsible party type: Principal Investigator
investigator affiliation: VA Pittsburgh Healthcare System
investigator full name: Jennifer Collinger
investigator title: Research Biomedical Engineer
mesh term: Spinal Cord Injuries
mesh term: Wounds and Injuries
sharing ipd: No
ipd description: Research information will not be shared with anyone outside of the research team.