<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/NCT04495075</url>
  </required_header>
  <id_info>
    <org_study_id>20441</org_study_id>
    <nct_id>NCT04495075</nct_id>
  </id_info>
  <brief_title>Neuromuscular Control in Individuals Following ACL-Reconstruction</brief_title>
  <official_title>The Use of Visuomotor Therapy to Modulate Corticospinal Excitability in Patients Following ACL-Reconstruction</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Virginia</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Virginia</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>
      The purpose of this study is to investigate the neurophysiological contributors to muscle&#xD;
      function following ACL Reconstruction and the influence of motor control biofeedback exercise&#xD;
      on measures of muscle function. The research team hypothesizes that the application of motor&#xD;
      biofeedback will increase cortical excitability of the quadriceps compared to the passive&#xD;
      movement of the knee.&#xD;
&#xD;
      This is a single session cross-over intervention study with a 1-week washout period between&#xD;
      treatment arms.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      1. Pre-treatment neuromuscular assessment Cortical Active Motor Threshed We will measure&#xD;
           motor evoked potentials with the use of a Transcranial magnetic stimulator (MagStim&#xD;
           model 200, Magstim Co., Ltd., Wales, UK). The MagStim has FDA 510K Clearance for&#xD;
           stimulation of peripheral nerves.&#xD;
&#xD;
             -  The participant will be asked to sit in the dynamometer (Biodex, System 3) in knee&#xD;
                extension at 90 degrees of knee flexion.&#xD;
&#xD;
             -  EMG electrodes will be placed on the distal quadriceps&#xD;
&#xD;
                o Local shaving, debridement, and cleaning will be done prior if necessary&#xD;
&#xD;
             -  A non-latex swim cap will be placed on the participants head for investigator's&#xD;
                measurements&#xD;
&#xD;
             -  Briefly, a magnetic field with a maximum value of 2.2 Tesla will be introduced to&#xD;
                the scalp at a location in the pre-motor cortex that corresponds to the quadriceps.&#xD;
                Single pulse stimulations will be delivered with no less than 10 seconds between&#xD;
                stimulations (maximum = 0.1 Hz).&#xD;
&#xD;
             -  When the magnetic field is received at the premotor cortex at the appropriate area,&#xD;
                a motor signal is sent to the quadriceps. We will record this signal with surface&#xD;
                EMG electrodes that are on the quadriceps.&#xD;
&#xD;
             -  The participant will be asked to extend their leg to match a force equivalent to 5%&#xD;
                MVIC. Feedback will be provided to the participant to provide such force.&#xD;
&#xD;
             -  Stimulation of the TMS will happen once every ten seconds until the Active Motor&#xD;
                Threshold was found by the investigator.&#xD;
&#xD;
                  -  The motor evoked potential measured by the quadriceps will be recorded at 80%,&#xD;
                     90%, 100%, 110%, 120%, 130%, 140%, and 150% of the patients Active motor&#xD;
                     threshold.&#xD;
&#xD;
        2. Patient randomization&#xD;
&#xD;
           - The patient is then randomized to 1 of 2 treatment arms. 1) Visuomotor Therapy or 2)&#xD;
           Passive Motion&#xD;
&#xD;
        3. Perform Randomized Treatment Visuomotor Therapy&#xD;
&#xD;
             -  The participant will sit in the Biodex chair with the tested limb secured in the&#xD;
                dynamometer&#xD;
&#xD;
             -  The participant will receive live real-time biofeedback of their knee force output&#xD;
                (no more than 30% of maximum force)&#xD;
&#xD;
             -  The participant will aim to match their force output to a target threshold&#xD;
                presented on the screen.&#xD;
&#xD;
             -  The participant will complete 10 60-second trials of this exercise with a 30 second&#xD;
                rest between each trial.&#xD;
&#xD;
           OR&#xD;
&#xD;
           Passive Motion&#xD;
&#xD;
             -  The participant will sit in the Biodex chair with the tested limb secured in the&#xD;
                dynamometer&#xD;
&#xD;
             -  The dynamometer will passively move the patients lower limb between 80 to 120&#xD;
                degrees of knee flexion&#xD;
&#xD;
             -  The participant will be asked to relax for the duration of testing - The&#xD;
                participant will complete 10 60-second trials of this exercise with a 30 second&#xD;
                rest between each trial.&#xD;
&#xD;
        4. Reassess Neuromuscular outcome (Step 1)&#xD;
&#xD;
        5. 1-week washout period&#xD;
&#xD;
        6. Repeat Steps 1 through 4 but the patient receives the cross-over arm intervention&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Actual">March 1, 2020</completion_date>
  <primary_completion_date type="Actual">March 1, 2020</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>Laboratory Controlled Crossover Study</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
    <masking_description>Assessing investigator was blinded to the intervention that was received by the participant.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Quadriceps Motor Evoked Potential (micoVolts) PreSham (Passive Motion)</measure>
    <time_frame>6-months post-Anterior Cruciate Ligament Reconstruction</time_frame>
    <description>Activation of the Quadriceps muscle through stimulation of primary motor cortex. Measured Through electromyography on the vastus medialis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quadriceps Motor Evoked Potential (micoVolts) PostSham (Passive Motion)</measure>
    <time_frame>6-months post-Anterior Cruciate Ligament Reconstruction</time_frame>
    <description>Activation of the Quadriceps muscle through stimulation of primary motor cortex. Measured Through electromyography on the vastus medialis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Quadriceps Motor Evoked Potential - Sham (Passive Motion)</measure>
    <time_frame>6-months post-Anterior Cruciate Ligament Reconstruction</time_frame>
    <description>Difference in microVolts between pre-sham measure and post-sham measure</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quadriceps Motor Evoked Potential (micoVolts) PreActive (Visuomotor Therapy)</measure>
    <time_frame>6-months post-Anterior Cruciate Ligament Reconstruction</time_frame>
    <description>Activation of the Quadriceps muscle through stimulation of primary motor cortex. Measured Through electromyography on the vastus medialis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Quadriceps Motor Evoked Potential (micoVolts) PostActive (Visuomotor Therapy)</measure>
    <time_frame>6-months post-Anterior Cruciate Ligament Reconstruction</time_frame>
    <description>Activation of the Quadriceps muscle through stimulation of primary motor cortex. Measured Through electromyography on the vastus medialis</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change in Quadriceps Motor Evoked Potential - Active (Visuomotor Therapy)</measure>
    <time_frame>6-months post-Anterior Cruciate Ligament Reconstruction</time_frame>
    <description>Difference in microVolts between pre-active measure and post-active measure</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">10</enrollment>
  <condition>Anterior Cruciate Ligament Injuries</condition>
  <condition>Quadriceps Muscle Atrophy</condition>
  <arm_group>
    <arm_group_label>Visuomotor Therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Patients were seated in the isokinetic dynamometer with their hips flexed to 85º. A target sine wave with a maximum amplitude of 30% MVIC and a minimum amplitude of 5% MVIC and a frequency of 0.128 Hz was visually presented to the patient.31 The patient was instructed to match their torque to the presented target throughout the duration of testing. Each visuomotor therapy trial was 60-seconds, followed by 30-seconds of rest for 10 repetitions, totaling 15 minutes.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Passive Motion</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Patients were seated in the isokinetic dynamometer with their hips flexed to 85º. The dynamometer then passively moved the patient from 80º to 120º of knee flexion for 60-seconds, followed by 30-seconds of rest for 10 repetitions, totaling 15 minutes. The patient was provided visual feedback of their knee position throughout the trials. The patient was instructed to relax their knee throughout the intervention.</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Visuomotor Therapy</intervention_name>
    <description>The use of visual feedback informing internal physiological processes, such as muscle activation, torque, and joint position, has been termed &quot;visuomotor therapy&quot;. Visuomotor therapy encompasses completion of sub-maximal motor control tasks accompanying real-time visual biofeedback.</description>
    <arm_group_label>Visuomotor Therapy</arm_group_label>
    <other_name>Motor Biofeedback</other_name>
  </intervention>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Passive Motion</intervention_name>
    <description>The knee is passively moved through a range of motion.</description>
    <arm_group_label>Passive Motion</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  • Ages 18-45&#xD;
&#xD;
               -  At the time point of return to play progression following ACL Reconstruction&#xD;
&#xD;
               -  Physically active individuals based on current ACSM guidelines of 30 minutes of&#xD;
                  moderate-intensity daily physical activity three days a week)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects who are known to be pregnant (self-reported)&#xD;
&#xD;
               -  Subjects diagnosed with malignancy&#xD;
&#xD;
               -  Subjects with serious infection near the lower limb&#xD;
&#xD;
               -  Subjects with known muscular abnormalities&#xD;
&#xD;
               -  History of cardiopulmonary disorder&#xD;
&#xD;
               -  Subjects with a previous history of stroke&#xD;
&#xD;
               -  History of neurological or psychiatric disorders including poorly controlled&#xD;
                  migraine headaches, seizure disorder, history or immediate family history of&#xD;
                  seizures and/or epilepsy&#xD;
&#xD;
               -  Subjects with any type of neuropathy (numbness and tingling)&#xD;
&#xD;
               -  Subjects with a clinical diagnosis of multiple sclerosis (MS) or Parkinson's&#xD;
                  Disease&#xD;
&#xD;
               -  Implanted biomedical device (active or inactive implants (including device&#xD;
                  leads), including deep brain stimulators, cochlear implants, and vagus nerve&#xD;
                  stimulators)&#xD;
&#xD;
               -  History of skull fracture&#xD;
&#xD;
               -  Subjects who have any metal implants anywhere in their head, neck or shoulders&#xD;
&#xD;
               -  Patients taking any medications, which may influence cortical excitability, which&#xD;
                  could influence neurophysiologic measures) and affect objective clinical data&#xD;
                  (e.g. antispastics, anxiolytics, hypnotics, ant-epileptics)&#xD;
&#xD;
               -  Subjects who are prescribed medications which may influence cortical&#xD;
                  excitability, which could influence neurophysiologic measures) and affect&#xD;
                  objective clinical data (e.g. antispastics, anxiolytics, hypnotics,&#xD;
                  ant-epileptics), will not be able to remain in the study.&#xD;
&#xD;
               -  Unable to provide consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>45 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Joe M Hart, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Associate Professor</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Virginia</name>
      <address>
        <city>Charlottesville</city>
        <state>Virginia</state>
        <zip>22903</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>July 2020</verification_date>
  <study_first_submitted>July 21, 2020</study_first_submitted>
  <study_first_submitted_qc>July 28, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">July 31, 2020</study_first_posted>
  <last_update_submitted>July 28, 2020</last_update_submitted>
  <last_update_submitted_qc>July 28, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">July 31, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>University of Virginia</investigator_affiliation>
    <investigator_full_name>Joseph Hart</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Muscular Atrophy</mesh_term>
    <mesh_term>Anterior Cruciate Ligament 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/NCT04495075
org study id: 20441
nct id: NCT04495075
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The purpose of this study is to investigate the neurophysiological contributors to muscle
      function following ACL Reconstruction and the influence of motor control biofeedback exercise
      on measures of muscle function. The research team hypothesizes that the application of motor
      biofeedback will increase cortical excitability of the quadriceps compared to the passive
      movement of the knee.

      This is a single session cross-over intervention study with a 1-week washout period between
      treatment arms.
1. Pre-treatment neuromuscular assessment Cortical Active Motor Threshed We will measure
           motor evoked potentials with the use of a Transcranial magnetic stimulator (MagStim
           model 200, Magstim Co., Ltd., Wales, UK). The MagStim has FDA 510K Clearance for
           stimulation of peripheral nerves.

             -  The participant will be asked to sit in the dynamometer (Biodex, System 3) in knee
                extension at 90 degrees of knee flexion.

             -  EMG electrodes will be placed on the distal quadriceps

                o Local shaving, debridement, and cleaning will be done prior if necessary

             -  A non-latex swim cap will be placed on the participants head for investigator's
                measurements

             -  Briefly, a magnetic field with a maximum value of 2.2 Tesla will be introduced to
                the scalp at a location in the pre-motor cortex that corresponds to the quadriceps.
                Single pulse stimulations will be delivered with no less than 10 seconds between
                stimulations (maximum = 0.1 Hz).

             -  When the magnetic field is received at the premotor cortex at the appropriate area,
                a motor signal is sent to the quadriceps. We will record this signal with surface
                EMG electrodes that are on the quadriceps.

             -  The participant will be asked to extend their leg to match a force equivalent to 5%
                MVIC. Feedback will be provided to the participant to provide such force.

             -  Stimulation of the TMS will happen once every ten seconds until the Active Motor
                Threshold was found by the investigator.

                  -  The motor evoked potential measured by the quadriceps will be recorded at 80%,
                     90%, 100%, 110%, 120%, 130%, 140%, and 150% of the patients Active motor
                     threshold.

        2. Patient randomization

           - The patient is then randomized to 1 of 2 treatment arms. 1) Visuomotor Therapy or 2)
           Passive Motion

        3. Perform Randomized Treatment Visuomotor Therapy

             -  The participant will sit in the Biodex chair with the tested limb secured in the
                dynamometer

             -  The participant will receive live real-time biofeedback of their knee force output
                (no more than 30% of maximum force)

             -  The participant will aim to match their force output to a target threshold
                presented on the screen.

             -  The participant will complete 10 60-second trials of this exercise with a 30 second
                rest between each trial.

           OR

           Passive Motion

             -  The participant will sit in the Biodex chair with the tested limb secured in the
                dynamometer

             -  The dynamometer will passively move the patients lower limb between 80 to 120
                degrees of knee flexion

             -  The participant will be asked to relax for the duration of testing - The
                participant will complete 10 60-second trials of this exercise with a 30 second
                rest between each trial.

        4. Reassess Neuromuscular outcome (Step 1)

        5. 1-week washout period

        6. Repeat Steps 1 through 4 but the patient receives the cross-over arm intervention
allocation: Randomized
intervention model: Crossover Assignment
intervention model description: Laboratory Controlled Crossover Study
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
masking description: Assessing investigator was blinded to the intervention that was received by the participant.
measure: Quadriceps Motor Evoked Potential (micoVolts) PreSham (Passive Motion)
time frame: 6-months post-Anterior Cruciate Ligament Reconstruction
description: Activation of the Quadriceps muscle through stimulation of primary motor cortex. Measured Through electromyography on the vastus medialis
measure: Quadriceps Motor Evoked Potential (micoVolts) PostSham (Passive Motion)
time frame: 6-months post-Anterior Cruciate Ligament Reconstruction
description: Activation of the Quadriceps muscle through stimulation of primary motor cortex. Measured Through electromyography on the vastus medialis
measure: Change in Quadriceps Motor Evoked Potential - Sham (Passive Motion)
time frame: 6-months post-Anterior Cruciate Ligament Reconstruction
description: Difference in microVolts between pre-sham measure and post-sham measure
measure: Quadriceps Motor Evoked Potential (micoVolts) PreActive (Visuomotor Therapy)
time frame: 6-months post-Anterior Cruciate Ligament Reconstruction
description: Activation of the Quadriceps muscle through stimulation of primary motor cortex. Measured Through electromyography on the vastus medialis
measure: Quadriceps Motor Evoked Potential (micoVolts) PostActive (Visuomotor Therapy)
time frame: 6-months post-Anterior Cruciate Ligament Reconstruction
description: Activation of the Quadriceps muscle through stimulation of primary motor cortex. Measured Through electromyography on the vastus medialis
measure: Change in Quadriceps Motor Evoked Potential - Active (Visuomotor Therapy)
time frame: 6-months post-Anterior Cruciate Ligament Reconstruction
description: Difference in microVolts between pre-active measure and post-active measure
arm group label: Visuomotor Therapy
arm group type: Experimental
description: Patients were seated in the isokinetic dynamometer with their hips flexed to 85º. A target sine wave with a maximum amplitude of 30% MVIC and a minimum amplitude of 5% MVIC and a frequency of 0.128 Hz was visually presented to the patient.31 The patient was instructed to match their torque to the presented target throughout the duration of testing. Each visuomotor therapy trial was 60-seconds, followed by 30-seconds of rest for 10 repetitions, totaling 15 minutes.
arm group label: Passive Motion
arm group type: Active Comparator
description: Patients were seated in the isokinetic dynamometer with their hips flexed to 85º. The dynamometer then passively moved the patient from 80º to 120º of knee flexion for 60-seconds, followed by 30-seconds of rest for 10 repetitions, totaling 15 minutes. The patient was provided visual feedback of their knee position throughout the trials. The patient was instructed to relax their knee throughout the intervention.
intervention type: Other
intervention name: Visuomotor Therapy
description: The use of visual feedback informing internal physiological processes, such as muscle activation, torque, and joint position, has been termed "visuomotor therapy". Visuomotor therapy encompasses completion of sub-maximal motor control tasks accompanying real-time visual biofeedback.
arm group label: Visuomotor Therapy
other name: Motor Biofeedback
intervention type: Other
intervention name: Passive Motion
description: The knee is passively moved through a range of motion.
arm group label: Passive Motion
criteria: 
gender: All
minimum age: 18 Years
maximum age: 45 Years
healthy volunteers: No
last name: Joe M Hart, PhD
role: Principal Investigator
affiliation: Associate Professor
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: University of Virginia
investigator full name: Joseph Hart
investigator title: Associate Professor
mesh term: Muscular Atrophy
mesh term: Anterior Cruciate Ligament Injuries
sharing ipd: No