<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/NCT03300258</url>
  </required_header>
  <id_info>
    <org_study_id>2016-1279</org_study_id>
    <secondary_id>A196200</secondary_id>
    <secondary_id>ENGR\MECHANICAL ENGR</secondary_id>
    <secondary_id>Protocol Version 1.8, 3/2017</secondary_id>
    <nct_id>NCT03300258</nct_id>
  </id_info>
  <brief_title>Robotic Pedaling Therapy for Targeted Neural Plasticity</brief_title>
  <official_title>Robotic Pedaling Therapy for Targeted Neural Plasticity</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>University of Wisconsin, Madison</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Wisconsin, Madison</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>
      The aim of this Pilot study is to determine whether robotically targeted lower-limb pedaling&#xD;
      therapy can increase the extent of stroke recovery on behavioral measures and induce brain&#xD;
      plasticity as measured by functional magnetic resonance imaging (fMRI). Forty (40) adult&#xD;
      stroke patients and 80 healthy controls will be enrolled in this study. Of the 40 patients,&#xD;
      half will be randomly assigned to the robotically-targeted training (&quot;robotic&quot;) group and&#xD;
      will receive training on the targeted training task. The other half of the patients will&#xD;
      perform a duration-matched aerobic pedaling exercise (&quot;control&quot; group). All stroke patients&#xD;
      will be scanned before and after their training program while performing or imagining simple&#xD;
      motor tasks. Behavioral assessments of motor and cognitive capacities will be collected at&#xD;
      each timepoint. Healthy control subjects enrolled for device testing (20) will receive up to&#xD;
      5 training sessions in a modified robotic paradigm and 1 fMRI scan, in order to investigate&#xD;
      motor learning and brain activity in a novel motor control task. Additional healthy pilot&#xD;
      subjects (up to 60) will test training protocols and assessments during preparatory design&#xD;
      phases of the project.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 1, 2019</start_date>
  <completion_date type="Actual">June 29, 2022</completion_date>
  <primary_completion_date type="Actual">June 29, 2022</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>Other</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Six Minute Walk Test (6MWT) Distance</measure>
    <time_frame>Baseline and at 5 weeks</time_frame>
    <description>A simple series of laps along a 30 m straight path in a level hallway.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Brain Activity in and near Affected Areas, through Functional MRI</measure>
    <time_frame>Baseline and at 5 weeks</time_frame>
    <description>fMRI scans will be used to measure task-specific cortical activity in sensorimotor areas during physical stepping with an MRI-compatible stepping machine, or imagined/visualized cycling.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Timed Up-and-Go Test (TUG)</measure>
    <time_frame>Baseline and at 5 weeks</time_frame>
    <description>A simple timed test of how long it takes to stand up, walk 10 feet, turn around, return to the starting point, and sit down.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Self-Selected Walking Speed (SSWS)</measure>
    <time_frame>Baseline and at 5 weeks</time_frame>
    <description>A simple test of the speed a person chooses to walk over a 5-meter distance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Fastest Comfortable Walking Speed (FCWS)</measure>
    <time_frame>Baseline and at 5 weeks</time_frame>
    <description>A similar test of the &quot;fastest comfortable speed&quot; a person can use to walk over the 5-meter distance</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Center of Pressure (COP) Characteristics</measure>
    <time_frame>Baseline and at 5 weeks</time_frame>
    <description>Movement of the Center of Pressure during standing, with eyes open and eyes closed. With eyes open, subjects focus their eyes on a spot on the wall in front of them. Metrics of COP control include excursion, average velocity, standard deviation, and an estimate of center of mass location.</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Actual">40</enrollment>
  <condition>Stroke</condition>
  <arm_group>
    <arm_group_label>Non-Stroke Pilot Group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Robotic therapy. Aerobic therapy. Subjects without stroke, pilot subjects tested during early phases while the device and therapeutic task specifications are developed, and throughout the project while the device and tasks are refined.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Non-Stroke Comparison Group</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Robotic therapy. Healthy controls enrolled (age 50-85) to contribute to a normative data set on motor learning using the robotic protocols designed for stroke.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Robotic Training Group</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Robotic therapy. Subjects with Stroke who will perform the targeted training task: exercise using novel tasks on a robotic recumbent cycle.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Aerobic Training Group</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Aerobic therapy. Subjects with Stroke who will perform aerobic pedaling, duration-matched to the Robotic group.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Robotic therapy</intervention_name>
    <description>The &quot;Robotic&quot; group will use a robotic training protocol to incentivize recovery of motor control by changing task demands throughout the training period. One or more target tasks will be chosen to mimic different sub-functions of gait, including some which are not normally excited in typical cycling behavior. Also, tasks may be designed to target non-gait motions such as hip ab/adduction. The required task may be changed periodically. This therapy protocol will occupy 30 minutes of each training session. Prior to testing, EMG electrodes will be placed on the major muscles of both legs, a procedure that takes roughly 15 minutes. Another 15 minutes is for changing clothes, briefing the subject, and other ancillary study activities. The total time per training session is 1 hour.</description>
    <arm_group_label>Non-Stroke Comparison Group</arm_group_label>
    <arm_group_label>Non-Stroke Pilot Group</arm_group_label>
    <arm_group_label>Robotic Training Group</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Aerobic therapy</intervention_name>
    <description>The Control group protocol is identical to that of the Robotic group, except the robotically-incentivized exercise is replaced with an aerobic exercise. This intervention emulates a commercial motorized exercise bike to improve cardiovascular unfitness contributions to gait impairment. This therapy implements assist-as-needed and constant-velocity control. The patient's target pedaling speed (e.g. 20 rev/min (to be finalized through pilot tests) and power level (set by heart rate to require approximately 50-70% of maximal oxygen uptake) are set at the beginning of each session and a motor provides assistance or resistance to compensate for the performance of the patient. The exercise will be performed in this mode for 30 minutes per training session.</description>
    <arm_group_label>Aerobic Training Group</arm_group_label>
    <arm_group_label>Non-Stroke Pilot Group</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Patients:&#xD;
&#xD;
        Inclusion criteria:&#xD;
&#xD;
          -  Subjects will be stroke patients with persistent moderate unilateral lower extremity&#xD;
             deficits, age 50-85 years at time of enrollment.&#xD;
&#xD;
          -  Time since stroke will be greater than 6 months (&quot;chronic&quot; stroke survivors).&#xD;
&#xD;
          -  Persistent moderate unilateral lower-limb impairment (defined as NIH Stroke Scale -&#xD;
             Motor Leg section score of 1-2, to be discussed with the patient verbally during phone&#xD;
             screening and assessed by the investigator during the initial enrollment visit).&#xD;
&#xD;
          -  Fluent in spoken and written English&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Allergy to electrode gel, surgical tape and metals.&#xD;
&#xD;
          -  Subjects under treatment for infectious diseases will be excluded from the study.&#xD;
&#xD;
          -  Women who are pregnant or planning to become pregnant during the course of the study&#xD;
             will be excluded.&#xD;
&#xD;
          -  Contraindications for MRI&#xD;
&#xD;
          -  Age over 85 years at time of enrollment.&#xD;
&#xD;
        Healthy Controls:&#xD;
&#xD;
        Inclusion criteria:&#xD;
&#xD;
          -  Ages 18-85 years&#xD;
&#xD;
          -  Non-Stroke Group 1 (&quot;Matched Controls&quot;): 50-85 years old at time of enrollment, to&#xD;
             match the population of stroke patients to be studied&#xD;
&#xD;
          -  Non-Stroke Group 2 (&quot;Pilot Controls&quot;): 18-50 years old at time of enrollment (Pilot&#xD;
             subjects to be initially enrolled early in the design phase of the study, and with&#xD;
             enrollment ongoing throughout the study to continue development.)&#xD;
&#xD;
          -  No known neurologic, psychiatric or developmental disability.&#xD;
&#xD;
          -  Fluent in spoken and written English&#xD;
&#xD;
        Exclusion criteria:&#xD;
&#xD;
          -  Allergy to electrode gel, surgical tape, and metals.&#xD;
&#xD;
          -  Subjects under treatment for infectious diseases will be excluded from the study.&#xD;
&#xD;
          -  Women who are pregnant or planning to become pregnant during the course of the study&#xD;
             will be excluded.&#xD;
&#xD;
          -  Contraindications for MRI&#xD;
&#xD;
          -  Age over 85 years at time of enrollment.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>85 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Peter G Adamczyk, Ph.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Wisconsin, Madison</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Wisconsin, Madison</name>
      <address>
        <city>Madison</city>
        <state>Wisconsin</state>
        <zip>53706</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>August 2022</verification_date>
  <study_first_submitted>June 12, 2017</study_first_submitted>
  <study_first_submitted_qc>September 27, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">October 3, 2017</study_first_posted>
  <last_update_submitted>August 9, 2022</last_update_submitted>
  <last_update_submitted_qc>August 9, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">August 10, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <pending_results>
    <submitted>August 15, 2023</submitted>
    <returned>September 11, 2023</returned>
    <submitted>September 12, 2023</submitted>
  </pending_results>
  <!-- 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/NCT03300258
org study id: 2016-1279
secondary id: A196200
secondary id: ENGR\MECHANICAL ENGR
secondary id: Protocol Version 1.8, 3/2017
nct id: NCT03300258
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
is us export: No
The aim of this Pilot study is to determine whether robotically targeted lower-limb pedaling
      therapy can increase the extent of stroke recovery on behavioral measures and induce brain
      plasticity as measured by functional magnetic resonance imaging (fMRI). Forty (40) adult
      stroke patients and 80 healthy controls will be enrolled in this study. Of the 40 patients,
      half will be randomly assigned to the robotically-targeted training ("robotic") group and
      will receive training on the targeted training task. The other half of the patients will
      perform a duration-matched aerobic pedaling exercise ("control" group). All stroke patients
      will be scanned before and after their training program while performing or imagining simple
      motor tasks. Behavioral assessments of motor and cognitive capacities will be collected at
      each timepoint. Healthy control subjects enrolled for device testing (20) will receive up to
      5 training sessions in a modified robotic paradigm and 1 fMRI scan, in order to investigate
      motor learning and brain activity in a novel motor control task. Additional healthy pilot
      subjects (up to 60) will test training protocols and assessments during preparatory design
      phases of the project.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Other
masking: None (Open Label)
measure: Change in Six Minute Walk Test (6MWT) Distance
time frame: Baseline and at 5 weeks
description: A simple series of laps along a 30 m straight path in a level hallway.
measure: Change in Brain Activity in and near Affected Areas, through Functional MRI
time frame: Baseline and at 5 weeks
description: fMRI scans will be used to measure task-specific cortical activity in sensorimotor areas during physical stepping with an MRI-compatible stepping machine, or imagined/visualized cycling.
measure: Change in Timed Up-and-Go Test (TUG)
time frame: Baseline and at 5 weeks
description: A simple timed test of how long it takes to stand up, walk 10 feet, turn around, return to the starting point, and sit down.
measure: Change in Self-Selected Walking Speed (SSWS)
time frame: Baseline and at 5 weeks
description: A simple test of the speed a person chooses to walk over a 5-meter distance
measure: Change in Fastest Comfortable Walking Speed (FCWS)
time frame: Baseline and at 5 weeks
description: A similar test of the "fastest comfortable speed" a person can use to walk over the 5-meter distance
measure: Change in Center of Pressure (COP) Characteristics
time frame: Baseline and at 5 weeks
description: Movement of the Center of Pressure during standing, with eyes open and eyes closed. With eyes open, subjects focus their eyes on a spot on the wall in front of them. Metrics of COP control include excursion, average velocity, standard deviation, and an estimate of center of mass location.
arm group label: Non-Stroke Pilot Group
arm group type: Other
description: Robotic therapy. Aerobic therapy. Subjects without stroke, pilot subjects tested during early phases while the device and therapeutic task specifications are developed, and throughout the project while the device and tasks are refined.
arm group label: Non-Stroke Comparison Group
arm group type: Other
description: Robotic therapy. Healthy controls enrolled (age 50-85) to contribute to a normative data set on motor learning using the robotic protocols designed for stroke.
arm group label: Robotic Training Group
arm group type: Experimental
description: Robotic therapy. Subjects with Stroke who will perform the targeted training task: exercise using novel tasks on a robotic recumbent cycle.
arm group label: Aerobic Training Group
arm group type: Active Comparator
description: Aerobic therapy. Subjects with Stroke who will perform aerobic pedaling, duration-matched to the Robotic group.
intervention type: Device
intervention name: Robotic therapy
description: The "Robotic" group will use a robotic training protocol to incentivize recovery of motor control by changing task demands throughout the training period. One or more target tasks will be chosen to mimic different sub-functions of gait, including some which are not normally excited in typical cycling behavior. Also, tasks may be designed to target non-gait motions such as hip ab/adduction. The required task may be changed periodically. This therapy protocol will occupy 30 minutes of each training session. Prior to testing, EMG electrodes will be placed on the major muscles of both legs, a procedure that takes roughly 15 minutes. Another 15 minutes is for changing clothes, briefing the subject, and other ancillary study activities. The total time per training session is 1 hour.
arm group label: Non-Stroke Comparison Group
arm group label: Non-Stroke Pilot Group
arm group label: Robotic Training Group
intervention type: Device
intervention name: Aerobic therapy
description: The Control group protocol is identical to that of the Robotic group, except the robotically-incentivized exercise is replaced with an aerobic exercise. This intervention emulates a commercial motorized exercise bike to improve cardiovascular unfitness contributions to gait impairment. This therapy implements assist-as-needed and constant-velocity control. The patient's target pedaling speed (e.g. 20 rev/min (to be finalized through pilot tests) and power level (set by heart rate to require approximately 50-70% of maximal oxygen uptake) are set at the beginning of each session and a motor provides assistance or resistance to compensate for the performance of the patient. The exercise will be performed in this mode for 30 minutes per training session.
arm group label: Aerobic Training Group
arm group label: Non-Stroke Pilot Group
criteria: 
gender: All
minimum age: 18 Years
maximum age: 85 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Peter G Adamczyk, Ph.D.
role: Principal Investigator
affiliation: University of Wisconsin, Madison
facility: 
country: United States
responsible party type: Sponsor
sharing ipd: No
submitted: August 15, 2023
returned: September 11, 2023
submitted: September 12, 2023