<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/NCT03773653</url>
  </required_header>
  <id_info>
    <org_study_id>201804087RINB</org_study_id>
    <nct_id>NCT03773653</nct_id>
  </id_info>
  <brief_title>Synergistic Bilateral Upper-Limb Stroke Rehabilitation Based on Robotic Priming Technique</brief_title>
  <official_title>Synergistic Bilateral Upper-Limb Stroke Rehabilitation Based on Robotic Priming Technique</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>National Taiwan University Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>National Taiwan University Hospital</source>
  <oversight_info>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      This comparative efficacy study will be based on a 3-armed controlled trial: bilateral&#xD;
      robotic priming combined with bilateral arm training (bilateral RT+BAT), bilateral robotic&#xD;
      priming combined with mirror therapy (bilateral RT+MT), and the control intervention&#xD;
      (bilateral RT+IOT). The goal of this 4-year project is to provide scientific evidence of the&#xD;
      comparative efficacy research of hybrid interventions based on unilateral vs. bilateral&#xD;
      approach to upper limb rehabilitation in subacute and chronic stroke.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This proposed research fits in the NHRI research priority 4-1 by addressing innovative&#xD;
      treatment strategies for stroke that is in desperate need of scientific scrutiny. Stroke is&#xD;
      one of the major medical conditions that lead to long-term disability and causes heavy health&#xD;
      care and financial burden. Advances in clinical and translational neurosciences have led to&#xD;
      the new development of stroke rehabilitation. Current stroke rehabilitation programs such as&#xD;
      robotic therapy, mirror therapy, and bilateral arm training are bilateral approaches to&#xD;
      intensive practice based on the tenet of practice-dependent neuroplasticity. Bilateral&#xD;
      robotic therapy can potentially be a movement-based priming technique to promote rebalancing&#xD;
      of cortical excitability and create an enriched neuroplastic environment by priming the brain&#xD;
      to facilitate motor and functional recovery. This proposed research project will: (1) examine&#xD;
      the effects of bilateral robotic priming combined with bilateral arm training approach versus&#xD;
      bilateral robotic priming combined with mirror therapy, relative to the control intervention&#xD;
      approach (bilateral robotic priming combined with impairment-oriented training) on&#xD;
      sensorimotor function, daily function, self-efficacy, quality of life, and motor control&#xD;
      strategy in patients with stroke, (2) investigate the 3-month retention effects of robotic&#xD;
      priming combined with contemporary rehabilitation approaches (i.e., bilateral arm training&#xD;
      and mirror therapy) and the control intervention, and (3) identify the potential predictors&#xD;
      of functionally relevant changes after therapy.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">November 12, 2018</start_date>
  <completion_date type="Anticipated">December 31, 2022</completion_date>
  <primary_completion_date type="Anticipated">December 31, 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>Treatment</primary_purpose>
    <masking>Single (Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change from Baseline Fugl-Meyer Assessment (FMA) at 6 weeks, and 18 weeks</measure>
    <time_frame>Baseline, 6 weeks, and 18 weeks</time_frame>
    <description>The upper-extremity subscale of the FMA will be used to assess motor impairment. FMA contains 33 items (scale 0-66). The higher summed score means the greater recovery of motor impairment.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline ABILHAND Questionnaire at 6 weeks, and 18 weeks</measure>
    <time_frame>Baseline, 6 weeks, and 18 weeks</time_frame>
    <description>The ABILHAND Questionnaire will be used to evaluate the ability of the upper limb in functional activities. ABILHAND contains 23 items (scale 0-69). The higher average score means the greater recovery of the ability of the upper limb in functional activities.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Change from Baseline Stroke Impact Scale Version 3.0 (SIS 3.0) at 6 weeks, and 18 weeks</measure>
    <time_frame>Baseline, 6 weeks, and 18 weeks</time_frame>
    <description>The SIS 3.0 is a stroke-specific health-related quality of life instrument. It consists of 59 items assessing 8 domains (i.e., strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion. memory and thinking and participation). Items are rated on a 5-point Likert scale, with lower scores indicating greater difficulty in task completion during the past week.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline Goal Attainment Scaling (GAS) at 6 weeks.</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>The GAS will be used for measurement the achievement of each participant's expectation in the course of intervention. The individual intervention goals related to daily activity will be negotiated by the therapists and participants. For the goals potentially achievable and not overly ambitious, each goal will be rated on a 5-point ordinal scale with the level of attainment captured. The importance and the difficulty for each goal will be scored also based on a 3-point ordinal scale (1 to 3). The overall GAS score will be calculated by a following formula and a GAS summed score larger than 50 refers to an above-expected performance.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline Functional Independence Measure (FIM) at 6 weeks</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>The FIM consists of 18 items (scale 18-126) grouped into 6 subscales measuring self-care, sphincter control, transfer, locomotion, communication, and social cognition ability. The higher summed score means the greater recovery of functional independence.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline Stroke Self Efficacy Questionnaire (SSEQ) at 6 weeks</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>The SSEQ will be used to measure participants' confidence in functional performance from stroke. It consists of 13 items (scale 0-130). A higher summed score (maximum score indicates higher self- efficacy in functional performance from stroke.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline Activity level as evaluated by actigraphy at 6 weeks</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>We will use the ActiGraph GX3 accelerometers (ActiGraph, Shalimar, FL, USA) to quantitatively measure the amount of use outside the laboratory settings. The accelerometer will record the number of moves each minute, and the average counts of move per minute will be calculated as the primary outcome measure.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline Possible adverse response at 6 weeks</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>The vertical numerical rating scale supplemented with a faces rating scale (NRS-FRS) and a self-reported assessment will be provided to evaluate adverse effects on fatigue and pain severity, respectively. Both assessments using 11-point scale (0 = no fatigue/pain to 10 = worst possible fatigue/pain) will be applied.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline Wolf Motor Function Test (WMFT) score at 6 weeks</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>The WMFT quantifies the motor functions of the upper limbs through timed and functional tasks.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline Revised Nottingham Sensory Assessment (rNSA) at 6 weeks</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>The rNSA will be used to evaluate changes in sensation. The rNSA using a 3-point or 4-point scale contains 72 items (scale 0-151) and is divided into tactile sensation, proprioception, and stereognosis subscales. The higher summed score means the greater recovery of sensory impairment.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline Medical Research Council scale (MRC) at 6 weeks</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>MRC will be used for measurement of muscle strength of the affected arm. MRC contains 8 items (scale 0-40). The higher summed score means the greater recovery of muscle strength of the affected arm.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from lateral pinch strength at 6 weeks</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>Lateral pinch strength will be used for measurement of muscle strength of the affected hand. The higher score means the greater recovery of muscle strength on the pinch strength.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change from Baseline Chedoke Arm and Hand Activity Inventory (CAHAI) score at 6 weeks</measure>
    <time_frame>Baseline and 6 weeks</time_frame>
    <description>The CAHAI quantifies the bilateral motor functions of the upper limbs through and functional tasks.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">96</enrollment>
  <condition>Stroke Rehabilitation</condition>
  <arm_group>
    <arm_group_label>BMT to be combined with BAT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this group will receive bilateral robotic priming and bilateral arm training or mirror therapy within the 90-minute training sessions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BMT to be combined with MT</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Participants in this group will receive bilateral robotic priming and mirror therapy within the 90-minute training sessions.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>BMT to be combined with IOT</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Participants in this group will receive bilateral robotic priming and impairment-oriented training within one 90-minute training session.</description>
  </arm_group>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>BMT to be combined with BAT</intervention_name>
    <description>Specifically, the participants will first receive 40 to 45 minutes of bilateral robotic priming using the BMT. After the robotic priming, participants will receive another 40 to 45 minutes training in tasks focusing on bilateral symmetric movements of both ULs.</description>
    <arm_group_label>BMT to be combined with BAT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>BMT to be combined with MT</intervention_name>
    <description>Similar to the RT+BAT group, the participants will first receive 40 to 45 minutes of bilateral robotic priming delivered by the BMT with the same priming protocol. After bilateral robotic priming, participants will receive 40 to 45 minutes of mirror therapy.</description>
    <arm_group_label>BMT to be combined with MT</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Behavioral</intervention_type>
    <intervention_name>BMT to be combined with IOT</intervention_name>
    <description>Similar to the RT+BAT group, the participants will first receive 40 to 45 minutes of bilateral robotic priming delivered by the BMT with the same priming protocol. After bilateral robotic priming, participants will receive 40 to 45 minutes of impairment-oriented training.</description>
    <arm_group_label>BMT to be combined with IOT</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        (1) ⩾3 months onset from a first-ever unilateral stroke; (2) age range from 18 to 80 years;&#xD;
        (3) baseline upper extremity motor score on the Fugl-Meyer Assessment &gt;10 (Fugl-Meyer et&#xD;
        al., 1975); (4) no severe spasticity in any joints of the affected arm (Modified Ashworth&#xD;
        Scale ⩽ 3) (Charalambous, 2014); (5) able to follow study instructions (Mini Mental State&#xD;
        Examination Score ⩾24) (Skidmore et al., 2010); (6) no serious vision deficits and no other&#xD;
        neurologic or major orthopedic diseases; (7) able to participate in a rehabilitation&#xD;
        intervention program for 6 weeks; and (8) no participation in other studies during the&#xD;
        study period and willing to provide written informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
        (1) acute inflammation and (2) major medical problems or poor physical conditions that&#xD;
        might interfere with participation.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Keh-chung Lin, ScD</last_name>
    <role>Principal Investigator</role>
    <affiliation>School of Occupational Therapy, National Taiwan University, Taipei, Taiwan</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Keh-chung Lin, ScD</last_name>
    <phone>+886-2-3366-8180</phone>
    <email>kehchunglin@ntu.edu.tw</email>
  </overall_contact>
  <location>
    <facility>
      <name>National Taiwan University Hospital</name>
      <address>
        <city>Taipei</city>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Keh-chung Lin, ScD</last_name>
    </contact>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>April 2022</verification_date>
  <study_first_submitted>November 13, 2018</study_first_submitted>
  <study_first_submitted_qc>December 10, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 12, 2018</study_first_posted>
  <last_update_submitted>April 20, 2022</last_update_submitted>
  <last_update_submitted_qc>April 20, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">April 28, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>stroke, robot-assisted therapy, mirror therapy</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</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/NCT03773653
org study id: 201804087RINB
nct id: NCT03773653
lead sponsor: 
is fda regulated drug: No
is fda regulated device: No
This comparative efficacy study will be based on a 3-armed controlled trial: bilateral
      robotic priming combined with bilateral arm training (bilateral RT+BAT), bilateral robotic
      priming combined with mirror therapy (bilateral RT+MT), and the control intervention
      (bilateral RT+IOT). The goal of this 4-year project is to provide scientific evidence of the
      comparative efficacy research of hybrid interventions based on unilateral vs. bilateral
      approach to upper limb rehabilitation in subacute and chronic stroke.
This proposed research fits in the NHRI research priority 4-1 by addressing innovative
      treatment strategies for stroke that is in desperate need of scientific scrutiny. Stroke is
      one of the major medical conditions that lead to long-term disability and causes heavy health
      care and financial burden. Advances in clinical and translational neurosciences have led to
      the new development of stroke rehabilitation. Current stroke rehabilitation programs such as
      robotic therapy, mirror therapy, and bilateral arm training are bilateral approaches to
      intensive practice based on the tenet of practice-dependent neuroplasticity. Bilateral
      robotic therapy can potentially be a movement-based priming technique to promote rebalancing
      of cortical excitability and create an enriched neuroplastic environment by priming the brain
      to facilitate motor and functional recovery. This proposed research project will: (1) examine
      the effects of bilateral robotic priming combined with bilateral arm training approach versus
      bilateral robotic priming combined with mirror therapy, relative to the control intervention
      approach (bilateral robotic priming combined with impairment-oriented training) on
      sensorimotor function, daily function, self-efficacy, quality of life, and motor control
      strategy in patients with stroke, (2) investigate the 3-month retention effects of robotic
      priming combined with contemporary rehabilitation approaches (i.e., bilateral arm training
      and mirror therapy) and the control intervention, and (3) identify the potential predictors
      of functionally relevant changes after therapy.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Change from Baseline Fugl-Meyer Assessment (FMA) at 6 weeks, and 18 weeks
time frame: Baseline, 6 weeks, and 18 weeks
description: The upper-extremity subscale of the FMA will be used to assess motor impairment. FMA contains 33 items (scale 0-66). The higher summed score means the greater recovery of motor impairment.
measure: Change from Baseline ABILHAND Questionnaire at 6 weeks, and 18 weeks
time frame: Baseline, 6 weeks, and 18 weeks
description: The ABILHAND Questionnaire will be used to evaluate the ability of the upper limb in functional activities. ABILHAND contains 23 items (scale 0-69). The higher average score means the greater recovery of the ability of the upper limb in functional activities.
measure: Change from Baseline Stroke Impact Scale Version 3.0 (SIS 3.0) at 6 weeks, and 18 weeks
time frame: Baseline, 6 weeks, and 18 weeks
description: The SIS 3.0 is a stroke-specific health-related quality of life instrument. It consists of 59 items assessing 8 domains (i.e., strength, hand function, activities of daily living/instrumental activities of daily living, mobility, communication, emotion. memory and thinking and participation). Items are rated on a 5-point Likert scale, with lower scores indicating greater difficulty in task completion during the past week.
measure: Change from Baseline Goal Attainment Scaling (GAS) at 6 weeks.
time frame: Baseline and 6 weeks
description: The GAS will be used for measurement the achievement of each participant's expectation in the course of intervention. The individual intervention goals related to daily activity will be negotiated by the therapists and participants. For the goals potentially achievable and not overly ambitious, each goal will be rated on a 5-point ordinal scale with the level of attainment captured. The importance and the difficulty for each goal will be scored also based on a 3-point ordinal scale (1 to 3). The overall GAS score will be calculated by a following formula and a GAS summed score larger than 50 refers to an above-expected performance.
measure: Change from Baseline Functional Independence Measure (FIM) at 6 weeks
time frame: Baseline and 6 weeks
description: The FIM consists of 18 items (scale 18-126) grouped into 6 subscales measuring self-care, sphincter control, transfer, locomotion, communication, and social cognition ability. The higher summed score means the greater recovery of functional independence.
measure: Change from Baseline Stroke Self Efficacy Questionnaire (SSEQ) at 6 weeks
time frame: Baseline and 6 weeks
description: The SSEQ will be used to measure participants' confidence in functional performance from stroke. It consists of 13 items (scale 0-130). A higher summed score (maximum score indicates higher self- efficacy in functional performance from stroke.
measure: Change from Baseline Activity level as evaluated by actigraphy at 6 weeks
time frame: Baseline and 6 weeks
description: We will use the ActiGraph GX3 accelerometers (ActiGraph, Shalimar, FL, USA) to quantitatively measure the amount of use outside the laboratory settings. The accelerometer will record the number of moves each minute, and the average counts of move per minute will be calculated as the primary outcome measure.
measure: Change from Baseline Possible adverse response at 6 weeks
time frame: Baseline and 6 weeks
description: The vertical numerical rating scale supplemented with a faces rating scale (NRS-FRS) and a self-reported assessment will be provided to evaluate adverse effects on fatigue and pain severity, respectively. Both assessments using 11-point scale (0 = no fatigue/pain to 10 = worst possible fatigue/pain) will be applied.
measure: Change from Baseline Wolf Motor Function Test (WMFT) score at 6 weeks
time frame: Baseline and 6 weeks
description: The WMFT quantifies the motor functions of the upper limbs through timed and functional tasks.
measure: Change from Baseline Revised Nottingham Sensory Assessment (rNSA) at 6 weeks
time frame: Baseline and 6 weeks
description: The rNSA will be used to evaluate changes in sensation. The rNSA using a 3-point or 4-point scale contains 72 items (scale 0-151) and is divided into tactile sensation, proprioception, and stereognosis subscales. The higher summed score means the greater recovery of sensory impairment.
measure: Change from Baseline Medical Research Council scale (MRC) at 6 weeks
time frame: Baseline and 6 weeks
description: MRC will be used for measurement of muscle strength of the affected arm. MRC contains 8 items (scale 0-40). The higher summed score means the greater recovery of muscle strength of the affected arm.
measure: Change from lateral pinch strength at 6 weeks
time frame: Baseline and 6 weeks
description: Lateral pinch strength will be used for measurement of muscle strength of the affected hand. The higher score means the greater recovery of muscle strength on the pinch strength.
measure: Change from Baseline Chedoke Arm and Hand Activity Inventory (CAHAI) score at 6 weeks
time frame: Baseline and 6 weeks
description: The CAHAI quantifies the bilateral motor functions of the upper limbs through and functional tasks.
arm group label: BMT to be combined with BAT
arm group type: Experimental
description: Participants in this group will receive bilateral robotic priming and bilateral arm training or mirror therapy within the 90-minute training sessions.
arm group label: BMT to be combined with MT
arm group type: Experimental
description: Participants in this group will receive bilateral robotic priming and mirror therapy within the 90-minute training sessions.
arm group label: BMT to be combined with IOT
arm group type: Active Comparator
description: Participants in this group will receive bilateral robotic priming and impairment-oriented training within one 90-minute training session.
intervention type: Behavioral
intervention name: BMT to be combined with BAT
description: Specifically, the participants will first receive 40 to 45 minutes of bilateral robotic priming using the BMT. After the robotic priming, participants will receive another 40 to 45 minutes training in tasks focusing on bilateral symmetric movements of both ULs.
arm group label: BMT to be combined with BAT
intervention type: Behavioral
intervention name: BMT to be combined with MT
description: Similar to the RT+BAT group, the participants will first receive 40 to 45 minutes of bilateral robotic priming delivered by the BMT with the same priming protocol. After bilateral robotic priming, participants will receive 40 to 45 minutes of mirror therapy.
arm group label: BMT to be combined with MT
intervention type: Behavioral
intervention name: BMT to be combined with IOT
description: Similar to the RT+BAT group, the participants will first receive 40 to 45 minutes of bilateral robotic priming delivered by the BMT with the same priming protocol. After bilateral robotic priming, participants will receive 40 to 45 minutes of impairment-oriented training.
arm group label: BMT to be combined with IOT
criteria: 
gender: All
minimum age: 18 Years
maximum age: 80 Years
healthy volunteers: No
last name: Keh-chung Lin, ScD
role: Principal Investigator
affiliation: School of Occupational Therapy, National Taiwan University, Taipei, Taiwan
last name: Keh-chung Lin, ScD
phone: +886-2-3366-8180
email: kehchunglin@ntu.edu.tw
facility: 
status: Recruiting
contact: 
country: Taiwan
responsible party type: Sponsor
mesh term: Stroke