<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/NCT03817086</url>
  </required_header>
  <id_info>
    <org_study_id>R970-17</org_study_id>
    <nct_id>NCT03817086</nct_id>
  </id_info>
  <brief_title>Physical and Mental Practice for Bimanual Coordination Rehabilitation</brief_title>
  <official_title>Combining Physical and Mental Practice for the Rehabilitation of Upper Extremity Movement Impairments Secondary to Traumatic Brain Injury</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Kessler Foundation</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Kessler Foundation</source>
  <oversight_info>
    <has_dmc>Yes</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>
      Traumatic Brain Injury (TBI)patients often suffer from loss of muscle strength in the hand&#xD;
      and foot, decrease in coordination and high muscle tone (spasticity). In this study,&#xD;
      investigators seek to compare how two different training programs can improve the&#xD;
      coordination and symptoms of fatigue in individuals with movement deficits secondary to TBI.&#xD;
      Using brain imaging, the study will also investigate changes in brain structure and activity&#xD;
      associated with hand movement.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Moderate and severe Traumatic Brain Injury (TBI) commonly causes upper extremity physical&#xD;
      impairments that persist even after years of injury; these deficits are attributed to damage&#xD;
      in brain structure and changes in structural and functional connectivity. Bimanual&#xD;
      coordination deficits and muscle weakness have a significant impact on TBI survivors'&#xD;
      well-being, and conventional therapy did not provide high success in treating these two&#xD;
      issues. The investigators relate this lag in efficiency to two main reasons: 1) absence of&#xD;
      outcome measures to quantify these deficits in a clinical setting, and 2) mental and&#xD;
      cognitive fatigue and short attention span in TBI survivors, which limits the feasibility to&#xD;
      enroll TBI survivors in intensive training protocols.&#xD;
&#xD;
      The investigators long-term goal is to provide effective rehabilitation training to help TBI&#xD;
      survivors in regaining proper bimanual coordination of hand movement and higher hand muscles'&#xD;
      strength. Mental practice includes motor imagery and action observation, and neural imaging&#xD;
      studies have shown that both motor imagery and action observation share similar neural&#xD;
      mechanism as movement execution. In addition, interventional studies have shown success in&#xD;
      combining physical and mental practice to improve motor function of stroke survivors, and it&#xD;
      does not induce muscle fatigue.&#xD;
&#xD;
      Hence, the first aim of this pilot study is to compare the therapeutic efficacy of combining&#xD;
      physical practice with mental practice (motor imagery and action observation) (MP) versus&#xD;
      physical practice only with action observation (PP) alone to improve hand bimanual&#xD;
      coordination and muscle strength of TBI survivors. Twenty subjects will be randomly and&#xD;
      equally assigned to either of two training groups. Maximum Voluntary Contraction (MVC),&#xD;
      Reaction Time (RT), and Percent of Error in Matching (PEM) a Target will be used as primary&#xD;
      outcome measures in addition to functional-based measures (Wolf Motor Function Test WMFT). In&#xD;
      addition, activation maps (functional MRI data) will be established for the brain neural&#xD;
      networks before and after training. The investigator's second aim is to study if either or&#xD;
      both interventions (MP and PP) induce reorganization in brain activity and in functional (at&#xD;
      rest) and effective (during a task) connectivity.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">June 28, 2017</start_date>
  <completion_date type="Actual">June 30, 2021</completion_date>
  <primary_completion_date type="Actual">May 30, 2021</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>Single (Participant)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Maximum voluntary contraction</measure>
    <time_frame>Pretest (before training), Posttest (immediately after end of training), Retention test (3 weeks after end of training)</time_frame>
    <description>maximum force exerted by each hand during squeezing a handgrip force sensor</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Reaction Time</measure>
    <time_frame>day 1, day 2, day 3, day 4, day 5, day 6, day 7, day 8, day 9, day 10, day 11, day 12</time_frame>
    <description>Reaction time is the time between real movement, and the time participant was instructed to move. This reaction time will be recorded for every training trial. The average of reaction time in each training day (total 12) will be used to examine the change in performance (slope) across the 12 training days, from day 1 until day 12 of the intervention.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Percent of Error in force matching</measure>
    <time_frame>day 1, day 2, day 3, day 4, day 5, day 6, day 7, day 8, day 9, day 10, day 11, day 12</time_frame>
    <description>Percent of error is the mismatch between the force exerted by the participant and the required force as per the instructions in each training trial. This Percent of Error will be recorded for every training trial. The average of errors in each training day (total 12) will be used to examine the change (slope) in performance across the 12 sessions (days) of the intervention.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in wolf motor function test</measure>
    <time_frame>Pretest (before training), Posttest (immediately after end of training), Retention test (4 weeks after end of training)</time_frame>
    <description>assessment of upper extremity function</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in within-brain effective connectivity</measure>
    <time_frame>Pretest (before training), Posttest (immediately after end of training)</time_frame>
    <description>connectivity between sensorimotor and attention network during inphase and out-phase hand coordination task</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in resting state function connectivity</measure>
    <time_frame>Pretest (before training), Posttest (immediately after end of training)</time_frame>
    <description>connectivity between sensorimotor and attention network at rest</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in brain structural connectivity (DTI)</measure>
    <time_frame>Pretest (before training), Posttest (immediately after end of training)</time_frame>
    <description>cerebrospinal tract connectivity</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>stroop effect test</measure>
    <time_frame>Pretest (before training), Posttest (immediately after end of training), Retention test (3 weeks after end of training)</time_frame>
    <description>neuropsychology assessments of reaction time</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>trail making test</measure>
    <time_frame>Pretest (before training), Posttest (immediately after end of training), Retention test (3 weeks after end of training)</time_frame>
    <description>neuropsychology assessments of task switching and visual attention</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">19</enrollment>
  <condition>Traumatic Brain Injury</condition>
  <condition>Weakness, Muscle</condition>
  <condition>Coordination Impairment</condition>
  <arm_group>
    <arm_group_label>Hand coordination and mental practice</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>In a total of 12 training sessions (days), 3 sessions per week over 4 weeks, participants practice physical in-phase and out-of-phase movement of both limbs for 40 minutes. Every 10 minutes, participants get a 2 minutes break during which the participants are asked to mentally imagine doing the task with an action observation of perfect performance.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hand coordination and action observation</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>In a total of 12 training sessions (days), 3 sessions per week over 4 weeks, participants practice physical in-phase and out-of-phase movement of both limbs for 40 minutes. Every 10 minutes, participants get a 2 minutes break during which the participants are asked to observe a visual feedback of performance.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Hand coordination and mental practice</intervention_name>
    <description>20 chronic (&gt;1year) moderate to severe TBI patients, with upper extremity movement deficits, will be randomly and equally assigned to two groups.&#xD;
In the experimental group, participants undergo 5 weeks (3 hrs/week) of physical practice training combined with mental practice (MP group).</description>
    <arm_group_label>Hand coordination and mental practice</arm_group_label>
    <other_name>experimental group</other_name>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>Hand coordination and action observation</intervention_name>
    <description>In the control group 2, participants undergo 5 weeks (3 hrs/week) of physical training (PP group).</description>
    <arm_group_label>Hand coordination and action observation</arm_group_label>
    <other_name>control group</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  between the ages of 20 to 60 years old.&#xD;
&#xD;
          -  have been diagnosed with a moderate to severe Traumatic Brain Injury.&#xD;
&#xD;
          -  must have had the injury more than 12 months ago.&#xD;
&#xD;
          -  have problems controlling my arm movements.&#xD;
&#xD;
          -  right handed.&#xD;
&#xD;
          -  speak and understand English.&#xD;
&#xD;
          -  willing and able to travel to Kessler Foundation in West Orange, NJ for the 3 testing&#xD;
             sessions and the 12 sessions of intervention.&#xD;
&#xD;
          -  must have stable health with no expected medication changes for the next 4 months.&#xD;
&#xD;
          -  able to understand instructions that are part of the testing and intervention.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  have had a penetrating Traumatic Brain Injury.&#xD;
&#xD;
          -  have severe spasticity (stiffness and tightness in my muscles) as determined by study&#xD;
             staff.&#xD;
&#xD;
          -  have had other brain injuries or illnesses in addition to the Traumatic Brain Injury&#xD;
             (for example, epilepsy, MS).&#xD;
&#xD;
          -  use illegal substances at this time, like drugs&#xD;
&#xD;
          -  have had a brain injury that was non-traumatic such as a stroke or brain tumor.&#xD;
&#xD;
          -  am enrolled in another research study that is likely to affect my participation in&#xD;
             this research study.&#xD;
&#xD;
          -  have a history of psychiatric illness (for example, bipolar disorder, schizophrenia,&#xD;
             or psychosis).&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>60 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Soha Saleh, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Kessler Foundation</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Kessler Foundation</name>
      <address>
        <city>West Orange</city>
        <state>New Jersey</state>
        <zip>07052</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>October 2022</verification_date>
  <study_first_submitted>January 10, 2019</study_first_submitted>
  <study_first_submitted_qc>January 24, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">January 25, 2019</study_first_posted>
  <last_update_submitted>October 12, 2022</last_update_submitted>
  <last_update_submitted_qc>October 12, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">October 14, 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 Weakness</mesh_term>
    <mesh_term>Brain Injuries</mesh_term>
    <mesh_term>Brain Injuries, Traumatic</mesh_term>
    <mesh_term>Ataxia</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/NCT03817086
org study id: R970-17
nct id: NCT03817086
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
Traumatic Brain Injury (TBI)patients often suffer from loss of muscle strength in the hand
      and foot, decrease in coordination and high muscle tone (spasticity). In this study,
      investigators seek to compare how two different training programs can improve the
      coordination and symptoms of fatigue in individuals with movement deficits secondary to TBI.
      Using brain imaging, the study will also investigate changes in brain structure and activity
      associated with hand movement.
Moderate and severe Traumatic Brain Injury (TBI) commonly causes upper extremity physical
      impairments that persist even after years of injury; these deficits are attributed to damage
      in brain structure and changes in structural and functional connectivity. Bimanual
      coordination deficits and muscle weakness have a significant impact on TBI survivors'
      well-being, and conventional therapy did not provide high success in treating these two
      issues. The investigators relate this lag in efficiency to two main reasons: 1) absence of
      outcome measures to quantify these deficits in a clinical setting, and 2) mental and
      cognitive fatigue and short attention span in TBI survivors, which limits the feasibility to
      enroll TBI survivors in intensive training protocols.

      The investigators long-term goal is to provide effective rehabilitation training to help TBI
      survivors in regaining proper bimanual coordination of hand movement and higher hand muscles'
      strength. Mental practice includes motor imagery and action observation, and neural imaging
      studies have shown that both motor imagery and action observation share similar neural
      mechanism as movement execution. In addition, interventional studies have shown success in
      combining physical and mental practice to improve motor function of stroke survivors, and it
      does not induce muscle fatigue.

      Hence, the first aim of this pilot study is to compare the therapeutic efficacy of combining
      physical practice with mental practice (motor imagery and action observation) (MP) versus
      physical practice only with action observation (PP) alone to improve hand bimanual
      coordination and muscle strength of TBI survivors. Twenty subjects will be randomly and
      equally assigned to either of two training groups. Maximum Voluntary Contraction (MVC),
      Reaction Time (RT), and Percent of Error in Matching (PEM) a Target will be used as primary
      outcome measures in addition to functional-based measures (Wolf Motor Function Test WMFT). In
      addition, activation maps (functional MRI data) will be established for the brain neural
      networks before and after training. The investigator's second aim is to study if either or
      both interventions (MP and PP) induce reorganization in brain activity and in functional (at
      rest) and effective (during a task) connectivity.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Participant)
measure: Change in Maximum voluntary contraction
time frame: Pretest (before training), Posttest (immediately after end of training), Retention test (3 weeks after end of training)
description: maximum force exerted by each hand during squeezing a handgrip force sensor
measure: Change in Reaction Time
time frame: day 1, day 2, day 3, day 4, day 5, day 6, day 7, day 8, day 9, day 10, day 11, day 12
description: Reaction time is the time between real movement, and the time participant was instructed to move. This reaction time will be recorded for every training trial. The average of reaction time in each training day (total 12) will be used to examine the change in performance (slope) across the 12 training days, from day 1 until day 12 of the intervention.
measure: Change in Percent of Error in force matching
time frame: day 1, day 2, day 3, day 4, day 5, day 6, day 7, day 8, day 9, day 10, day 11, day 12
description: Percent of error is the mismatch between the force exerted by the participant and the required force as per the instructions in each training trial. This Percent of Error will be recorded for every training trial. The average of errors in each training day (total 12) will be used to examine the change (slope) in performance across the 12 sessions (days) of the intervention.
measure: Change in wolf motor function test
time frame: Pretest (before training), Posttest (immediately after end of training), Retention test (4 weeks after end of training)
description: assessment of upper extremity function
measure: Change in within-brain effective connectivity
time frame: Pretest (before training), Posttest (immediately after end of training)
description: connectivity between sensorimotor and attention network during inphase and out-phase hand coordination task
measure: Change in resting state function connectivity
time frame: Pretest (before training), Posttest (immediately after end of training)
description: connectivity between sensorimotor and attention network at rest
measure: Change in brain structural connectivity (DTI)
time frame: Pretest (before training), Posttest (immediately after end of training)
description: cerebrospinal tract connectivity
measure: stroop effect test
time frame: Pretest (before training), Posttest (immediately after end of training), Retention test (3 weeks after end of training)
description: neuropsychology assessments of reaction time
measure: trail making test
time frame: Pretest (before training), Posttest (immediately after end of training), Retention test (3 weeks after end of training)
description: neuropsychology assessments of task switching and visual attention
arm group label: Hand coordination and mental practice
arm group type: Experimental
description: In a total of 12 training sessions (days), 3 sessions per week over 4 weeks, participants practice physical in-phase and out-of-phase movement of both limbs for 40 minutes. Every 10 minutes, participants get a 2 minutes break during which the participants are asked to mentally imagine doing the task with an action observation of perfect performance.
arm group label: Hand coordination and action observation
arm group type: Active Comparator
description: In a total of 12 training sessions (days), 3 sessions per week over 4 weeks, participants practice physical in-phase and out-of-phase movement of both limbs for 40 minutes. Every 10 minutes, participants get a 2 minutes break during which the participants are asked to observe a visual feedback of performance.
intervention type: Behavioral
intervention name: Hand coordination and mental practice
description: 20 chronic (>1year) moderate to severe TBI patients, with upper extremity movement deficits, will be randomly and equally assigned to two groups.
In the experimental group, participants undergo 5 weeks (3 hrs/week) of physical practice training combined with mental practice (MP group).
arm group label: Hand coordination and mental practice
other name: experimental group
intervention type: Behavioral
intervention name: Hand coordination and action observation
description: In the control group 2, participants undergo 5 weeks (3 hrs/week) of physical training (PP group).
arm group label: Hand coordination and action observation
other name: control group
criteria: 
gender: All
minimum age: 20 Years
maximum age: 60 Years
healthy volunteers: No
last name: Soha Saleh, PhD
role: Principal Investigator
affiliation: Kessler Foundation
facility: 
country: United States
responsible party type: Sponsor
mesh term: Muscle Weakness
mesh term: Brain Injuries
mesh term: Brain Injuries, Traumatic
mesh term: Ataxia
sharing ipd: No