<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/NCT01688856</url>
  </required_header>
  <id_info>
    <org_study_id>IRB12-00493</org_study_id>
    <secondary_id>R01HD068588</secondary_id>
    <nct_id>NCT01688856</nct_id>
  </id_info>
  <brief_title>Contralaterally Controlled FES of Arm &amp; Hand for Subacute Stroke Rehabilitation</brief_title>
  <official_title>Optimizing Contralaterally Controlled FES for Acute Upper Limb Hemiplegia</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>MetroHealth Medical Center</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Case Western Reserve University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Institutes of Health (NIH)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
    <collaborator>
      <agency>Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)</agency>
      <agency_class>NIH</agency_class>
    </collaborator>
  </sponsors>
  <source>MetroHealth Medical Center</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      Impaired arm and hand function is one of the most disabling and most common consequences of&#xD;
      stroke. The Investigators have developed Contralaterally Controlled Functional Electrical&#xD;
      Stimulation (CCFES), an innovative neuromuscular electrical stimulation (NMES) treatment for&#xD;
      improving the recovery of hand function after stroke. The purpose of this study is to&#xD;
      maximize the treatment effect of CCFES by adding stimulated elbow extension. The specific&#xD;
      aims and hypotheses are as follows:&#xD;
&#xD;
      AIM 1: Estimate the effect of Arm+Hand CCFES on upper limb motor impairment and activity&#xD;
      limitation.&#xD;
&#xD;
      Hypothesis 1: Stroke survivors treated with Arm+Hand CCFES have better outcomes on upper limb&#xD;
      impairment and activity limitation measures than those treated with dose-matched Arm+Hand&#xD;
      Cyclic NMES.&#xD;
&#xD;
      AIM 2: Estimate the effect of adding stimulated elbow extension to Hand CCFES.&#xD;
&#xD;
      Hypothesis 2: Stroke survivors treated with Arm+Hand CCFES will have greater reductions in&#xD;
      upper limb impairment and activity limitation than those treated with Hand CCFES.&#xD;
&#xD;
      AIM 3: Describe the relationship between treatment effect and time elapsed between stroke&#xD;
      onset and start of treatment.&#xD;
&#xD;
      Hypothesis 3: Patients who start Arm+Hand CCFES sooner after their stroke achieve better&#xD;
      outcomes.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Loss of arm and hand function is a severely disabling condition that occurs in nearly 75% of&#xD;
      the estimated 795,000 Americans who have a new or recurrent stroke each year [Roger 2011].&#xD;
      Upper limb impairment is often characterized by inability to extend the elbow and open the&#xD;
      hand. The hope of regaining lost motor function after stroke has been fueled in recent years&#xD;
      by the development of new rehabilitation therapies and devices that are aimed at promoting&#xD;
      the brain's capacity to reorganize after injury in such a way that restores motor control of&#xD;
      paretic limbs [Nudo 2001]. The Investigators' long-term objective is to develop stroke&#xD;
      rehabilitation treatments for the hemiparetic upper limb that are optimized for&#xD;
      effectiveness, applicability, and deployability.&#xD;
&#xD;
      The primary objective of this project is to estimate the effect of Arm+Hand Contralaterally&#xD;
      Controlled Functional Electrical Stimulation (CCFES) in reducing upper limb motor impairment&#xD;
      and activity limitation in subacute hemiplegia. CCFES is a treatment aimed at improving&#xD;
      recovery of volitional motor function in stroke survivors [Knutson 2007; Knutson 2009;&#xD;
      Knutson 2010]. Hand CCFES activates finger and thumb extensors with an intensity of&#xD;
      electrical stimulation that is proportional to the degree of opening of the contralateral&#xD;
      unimpaired hand wearing an instrumented glove. Thus, volitional opening of the nonparetic&#xD;
      hand produces stimulated opening of the paretic hand. The Hand CCFES system enables stroke&#xD;
      patients to use their impaired hand to practice functional tasks in therapy sessions. CCFES&#xD;
      incorporates the following features considered to be important to motor recovery and&#xD;
      promoting neuroplasticity: synchronization of motor intent with motor execution of paretic&#xD;
      hand opening [Rushton 2003; Kimberley 2004], bilateral symmetric movement [Luft 2004],&#xD;
      intensive repetitive hand opening exercises [Lang 2009], and the practice of functional tasks&#xD;
      [Nudo 2003]. In a pilot case series study of patients with chronic (&gt; 6 months) post-stroke&#xD;
      hemiplegia, all 6 participants experienced some reduction of upper limb motor impairment&#xD;
      after several weeks of Hand CCFES [Knutson 2007; Knutson 2009]. The results of a Phase I&#xD;
      randomized clinical trial (RCT) of Hand CCFES in 21 patients with subacute (≤ 6 months)&#xD;
      hemiplegia suggested that Hand CCFES may be superior to cyclic neuromuscular electrical&#xD;
      stimulation (NMES) in reducing upper extremity impairment and activity limitation [Knutson&#xD;
      2011].&#xD;
&#xD;
      In this study, added to the Hand CCFES treatment is stimulated elbow extension controlled by&#xD;
      the contralateral elbow. This &quot;next generation&quot; CCFES treatment is called Arm+Hand CCFES.&#xD;
      Arm+Hand CCFES therapy is intended to strengthen and improve the motor control of the&#xD;
      proximal upper limb as well as the hand, to improve simultaneous reaching and hand opening, a&#xD;
      functionally critical movement pattern that is often prevented by paresis and post-stroke&#xD;
      flexor synergies. The secondary objective of this project is to evaluate the effect of adding&#xD;
      elbow extensor stimulation to the Hand CCFES treatment.&#xD;
&#xD;
      Stroke survivors who are ≤ 2 years post-stroke with upper limb hemiplegia will be randomly&#xD;
      assigned to receive 12 weeks of either Arm+Hand CCFES (stimulates elbow extension and hand&#xD;
      opening), Hand CCFES (stimulates hand opening), or Arm+Hand Cyclic NMES (stimulates elbow&#xD;
      extension and hand opening but with pre-set timing and intensity, i.e., not&#xD;
      intention-driven), plus lab-based therapist-guided task practice. Upper limb impairment and&#xD;
      activity limitation will be assessed at baseline, 6, 12, 20, 28, and 36 weeks.&#xD;
&#xD;
      This is the first randomized controlled trial of Arm+Hand CCFES in subacute upper extremity&#xD;
      hemiplegia. Ultimately, the information learned in this study will serve to accelerate the&#xD;
      development of a new treatment for reducing post-stroke disability.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">January 2013</start_date>
  <completion_date type="Actual">August 31, 2018</completion_date>
  <primary_completion_date type="Actual">August 2018</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 in Box and Block Test (BBT) Score at 6 Months Post-Treatment</measure>
    <time_frame>2 timepoints: prior to treatment, 6 months post-treatment</time_frame>
    <description>The BBT counts how many blocks a participant can pick up, move over a barrier, and release in 60 seconds. Higher scores mean a better outcome.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in Reachable Workspace (RW) at 6 Months Post-Treatment</measure>
    <time_frame>2 timepoints: prior to treatment, 6 months post-treatment</time_frame>
    <description>Reachable Workspace (RW) is the area (cm^2) traced out when reaching for a target moving in a circular path just outside the reach of the participant.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Upper Extremity Fugl-Meyer (UEFM) Score at 6 Months Post-Treatment</measure>
    <time_frame>2 timepoints: prior to treatment, 6 months post-treatment</time_frame>
    <description>The Upper Extremity Fugl-Meyer (UEFM) is an assessment of motor impairment of the upper limb in which the participant is asked to make specific movements of the arm, forearm, wrist, and hand. Each movement is scored 0, 1, or 2 and the subscores are summed.&#xD;
Min=0; Max=66. Higher scores mean a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Stroke Upper Limb Capacity Scale (SULCS) at 6 Months Post-Treatment</measure>
    <time_frame>2 timepoints: prior to treatment, 6 months post-treatment</time_frame>
    <description>Stroke Upper Limb Capacity Scale (SULCS) is a 10-item test in which participants are given a score of 0 or 1 on their performance of tasks requiring varying degrees of upper limb capacity.&#xD;
Min=0; Max=10. Higher scores mean a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Arm Motor Abilities Test (AMAT) at 6 Months Post-Treatment</measure>
    <time_frame>2 timepoints: prior to treatment, 6 months post-treatment</time_frame>
    <description>The Arm Motor Abilities Test (AMAT) is an assessment of the participant's ability to do 9 standardized upper limb tasks. Each task is composed of 1 to 3 component tasks, each of which is rated on an ordinal scale of 0 to 5. The final score is the average of all component task scores across all 9 compound tasks.&#xD;
Min=0; Max=5. Higher scores mean a better outcome.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">67</enrollment>
  <condition>Stroke</condition>
  <condition>Hemiparesis</condition>
  <condition>Hemiplegia</condition>
  <arm_group>
    <arm_group_label>Arm+Hand CCFES</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Uses an electrical stimulator that opens the paretic hand and extends the paretic elbow in response to and with an intensity proportional to movement of the contralateral arm and hand. The treatment dose will be approximately 2 hrs per day of self-administered stimulation-mediated exercise at home plus 70 min of functional task practice twice a week in the laboratory for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Hand CCFES</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Uses an electrical stimulator that opens the paretic hand in response to and with an intensity proportional to movement of the contralateral hand. The treatment dose will be approximately 2 hrs per day of self-administered stimulation-mediated exercise at home plus 70 min of functional task practice twice a week in the laboratory for 12 weeks.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Arm+Hand Cyclic NMES</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Uses an electrical stimulator that delivers stimulation to open the hand and extend the elbow repeatedly with preprogrammed timing and intensity. The treatment dose will be approximately 2 hrs per day of self-administered stimulation-mediated exercise at home plus 70 min of functional task practice twice a week in the laboratory for 12 weeks.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Electrical Stimulator</intervention_name>
    <description>The 12-week treatment period consists of two components:&#xD;
Therapist-guided task practice performed 70 minutes twice a week in the research laboratory. If Arm+Hand CCFES or Hand CCFES, the stimulator is used during task practice.&#xD;
Self-administered muscle stimulation exercise performed 10 sessions per week at home using the device. If Arm+Hand CCFES or Hand CCFES, each session is 46 minutes. If Arm+Hand Cyclic NMES, each session is 60 minutes.</description>
    <arm_group_label>Arm+Hand CCFES</arm_group_label>
    <arm_group_label>Arm+Hand Cyclic NMES</arm_group_label>
    <arm_group_label>Hand CCFES</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Age ≥ 21 and ≤ 80&#xD;
&#xD;
          -  ≤ 2 years of first clinical hemorrhagic or nonhemorrhagic stroke&#xD;
&#xD;
          -  Skin intact on hemiparetic arm and hand&#xD;
&#xD;
          -  Able to follow 3-stage commands&#xD;
&#xD;
          -  Able to recall 2 of 3 items after 30 minutes&#xD;
&#xD;
          -  Medically stable&#xD;
&#xD;
          -  Finger extensor paresis indicated by a score of ≤ 4 out of 5 on the manual muscle test&#xD;
             (Medical Research Council scale)&#xD;
&#xD;
          -  Adequate movement of shoulder and elbow to position the paretic hand in the workspace&#xD;
             for table-top task practice&#xD;
&#xD;
          -  Caregiver available to assist with device daily - OR - able to independently don elbow&#xD;
             cuff on unaffected arm&#xD;
&#xD;
          -  Full volitional elbow extension/flexion and hand opening/closing of unaffected limb&#xD;
&#xD;
          -  Upper extremity hand section of Upper Extremity Fugl-Meyer (UEFM)≥ 1 AND ≤ 11/14&#xD;
&#xD;
          -  Unable to simultaneously fully extend the elbow and fully open the hand toward&#xD;
             tabletop object with arm unsupported (i.e. cannot voluntarily achieve the maximum&#xD;
             passive range of motion (PROM) available)&#xD;
&#xD;
          -  Functional PROM (minimal resistance) at shoulder, elbow, wrist, and hand&#xD;
             simultaneously on affected side (i.e., there exists enough PROM to reach and acquire&#xD;
             table-top objects).&#xD;
&#xD;
          -  Able to hear and respond to stimulator cues&#xD;
&#xD;
          -  While relaxed, surface NMES of finger extensors and thumb extensors and/or abductors&#xD;
             produces a functional degree of hand opening without pain.&#xD;
&#xD;
          -  While relaxed with the forearm supported with a mobile arm support, surface NMES of&#xD;
             elbow extensors (triceps) produces functional elbow extension without pain.&#xD;
&#xD;
          -  Patient must be able to sit unassisted in an armless straight-back chair for the&#xD;
             duration of the screening portion of the eligibility assessment.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Co-existing neurological condition other than prior stroke involving the hemiparetic&#xD;
             upper limb (e.g., peripheral nerve injury, Parkinson's Disease, Spinal Cord Injury,&#xD;
             Traumatic Brain Injury, Multiple Sclerosis).&#xD;
&#xD;
          -  Severely impaired cognition and communication&#xD;
&#xD;
          -  Uncontrolled seizure disorder&#xD;
&#xD;
          -  History of cardiac arrhythmias with hemodynamic instability&#xD;
&#xD;
          -  Cardiac pacemaker or other implanted electronic device&#xD;
&#xD;
          -  Pregnant&#xD;
&#xD;
          -  IM Botox injections in any UE muscle in the last 3 months&#xD;
&#xD;
          -  Insensate arm, forearm, or hand&#xD;
&#xD;
          -  Uncompensated hemi-neglect (extinguishing to double simultaneous stimulation)&#xD;
&#xD;
          -  Severe shoulder or hand pain&#xD;
&#xD;
          -  Severe depression on Beck Depression Inventory (BDI) (score&gt;=13 on BDI-fast screen)&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>80 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Jayme S. Knutson, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>MetroHealth Medical Center</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>MetroHealth Medical Center</name>
      <address>
        <city>Cleveland</city>
        <state>Ohio</state>
        <zip>44109</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <link>
    <url>http://fescenter.org/index.php</url>
    <description>Cleveland FES Center</description>
  </link>
  <reference>
    <citation>Nudo RJ, Plautz EJ, Frost SB. Role of adaptive plasticity in recovery of function after damage to motor cortex. Muscle Nerve. 2001 Aug;24(8):1000-19. doi: 10.1002/mus.1104.</citation>
    <PMID>11439375</PMID>
  </reference>
  <reference>
    <citation>Knutson JS, Harley MY, Hisel TZ, Chae J. Improving hand function in stroke survivors: a pilot study of contralaterally controlled functional electric stimulation in chronic hemiplegia. Arch Phys Med Rehabil. 2007 Apr;88(4):513-20. doi: 10.1016/j.apmr.2007.01.003.</citation>
    <PMID>17398254</PMID>
  </reference>
  <reference>
    <citation>Knutson JS, Hisel TZ, Harley MY, Chae J. A novel functional electrical stimulation treatment for recovery of hand function in hemiplegia: 12-week pilot study. Neurorehabil Neural Repair. 2009 Jan;23(1):17-25. doi: 10.1177/1545968308317577. Epub 2008 Sep 23.</citation>
    <PMID>18812432</PMID>
  </reference>
  <reference>
    <citation>Knutson JS, Chae J. A novel neuromuscular electrical stimulation treatment for recovery of ankle dorsiflexion in chronic hemiplegia: a case series pilot study. Am J Phys Med Rehabil. 2010 Aug;89(8):672-82. doi: 10.1097/PHM.0b013e3181e29bd7.</citation>
    <PMID>20531158</PMID>
  </reference>
  <reference>
    <citation>Kimberley TJ, Lewis SM, Auerbach EJ, Dorsey LL, Lojovich JM, Carey JR. Electrical stimulation driving functional improvements and cortical changes in subjects with stroke. Exp Brain Res. 2004 Feb;154(4):450-60. doi: 10.1007/s00221-003-1695-y. Epub 2003 Nov 15.</citation>
    <PMID>14618287</PMID>
  </reference>
  <reference>
    <citation>Rushton DN. Functional electrical stimulation and rehabilitation--an hypothesis. Med Eng Phys. 2003 Jan;25(1):75-8. doi: 10.1016/s1350-4533(02)00040-1.</citation>
    <PMID>12485788</PMID>
  </reference>
  <reference>
    <citation>Luft AR, McCombe-Waller S, Whitall J, Forrester LW, Macko R, Sorkin JD, Schulz JB, Goldberg AP, Hanley DF. Repetitive bilateral arm training and motor cortex activation in chronic stroke: a randomized controlled trial. JAMA. 2004 Oct 20;292(15):1853-61. doi: 10.1001/jama.292.15.1853. Erratum In: JAMA. 2004 Nov 24;292(20):2470.</citation>
    <PMID>15494583</PMID>
  </reference>
  <reference>
    <citation>Lang CE, Macdonald JR, Reisman DS, Boyd L, Jacobson Kimberley T, Schindler-Ivens SM, Hornby TG, Ross SA, Scheets PL. Observation of amounts of movement practice provided during stroke rehabilitation. Arch Phys Med Rehabil. 2009 Oct;90(10):1692-8. doi: 10.1016/j.apmr.2009.04.005.</citation>
    <PMID>19801058</PMID>
  </reference>
  <reference>
    <citation>Nudo RJ. Adaptive plasticity in motor cortex: implications for rehabilitation after brain injury. J Rehabil Med. 2003 May;(41 Suppl):7-10. doi: 10.1080/16501960310010070.</citation>
    <PMID>12817650</PMID>
  </reference>
  <reference>
    <citation>Knutson JS, Harley MY, Hisel TZ, Hogan SD, Maloney MM, Chae J. Contralaterally controlled functional electrical stimulation for upper extremity hemiplegia: an early-phase randomized clinical trial in subacute stroke patients. Neurorehabil Neural Repair. 2012 Mar-Apr;26(3):239-46. doi: 10.1177/1545968311419301. Epub 2011 Aug 29.</citation>
    <PMID>21875892</PMID>
  </reference>
  <reference>
    <citation>Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho PM, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs JB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Rosamond WD, Sorlie PD, Stafford RS, Turan TN, Turner MB, Wong ND, Wylie-Rosett J; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. 2011 Feb 1;123(4):e18-e209. doi: 10.1161/CIR.0b013e3182009701. Epub 2010 Dec 15. Erratum In: Circulation. 2011 Feb 15;123(6):e240. Circulation. 2011 Oct 18;124(16):e426.</citation>
    <PMID>21160056</PMID>
  </reference>
  <verification_date>January 2020</verification_date>
  <study_first_submitted>September 17, 2012</study_first_submitted>
  <study_first_submitted_qc>September 19, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">September 20, 2012</study_first_posted>
  <results_first_submitted>December 18, 2019</results_first_submitted>
  <results_first_submitted_qc>January 6, 2020</results_first_submitted_qc>
  <results_first_posted type="Actual">January 9, 2020</results_first_posted>
  <last_update_submitted>January 6, 2020</last_update_submitted>
  <last_update_submitted_qc>January 6, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">January 9, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>MetroHealth Medical Center</investigator_affiliation>
    <investigator_full_name>Jayme Knutson</investigator_full_name>
    <investigator_title>Assistant Professor, Physical Medicine and Rehabilitation</investigator_title>
  </responsible_party>
  <keyword>hand</keyword>
  <keyword>arm</keyword>
  <keyword>stroke</keyword>
  <keyword>hemiplegia</keyword>
  <keyword>electrical stimulation</keyword>
  <keyword>recovery</keyword>
  <keyword>rehabilitation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Hemiplegia</mesh_term>
    <mesh_term>Paresis</mesh_term>
  </condition_browse>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol and Statistical Analysis Plan</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>No</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>February 1, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/56/NCT01688856/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Arm+Hand CCFES</title>
          <description>Uses an electrical stimulator that opens the paretic hand and extends the paretic elbow in response to and with an intensity proportional to movement of the contralateral arm and hand.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided CCFES-mediated task practice performed 70 minutes twice a week in the research laboratory.&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 46 min/session.</description>
        </group>
        <group group_id="P2">
          <title>Hand CCFES</title>
          <description>Uses an electrical stimulator that opens the paretic hand in response to and with an intensity proportional to movement of the contralateral hand.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided CCFES-mediated task practice performed 70 minutes twice a week in the research laboratory.&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 46 min/session.</description>
        </group>
        <group group_id="P3">
          <title>Arm+Hand Cyclic NMES</title>
          <description>Uses an electrical stimulator that delivers stimulation to open the hand and extend the elbow repeatedly with preprogrammed timing and intensity.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided task practice performed 70 minutes twice a week in the research laboratory. (Stimulator not used during these sessions. To ensure that all 3 groups receive an equivalent dose of stimulation, this group has slightly lengthened self-administered hand opening exercise sessions at home.)&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 60 min/session.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="28"/>
                <participants group_id="P2" count="28"/>
                <participants group_id="P3" count="11"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="21"/>
                <participants group_id="P2" count="24"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="7"/>
                <participants group_id="P2" count="4"/>
                <participants group_id="P3" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Arm+Hand CCFES</title>
          <description>Uses an electrical stimulator that opens the paretic hand and extends the paretic elbow in response to and with an intensity proportional to movement of the contralateral arm and hand.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided CCFES-mediated task practice performed 70 minutes twice a week in the research laboratory.&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 46 min/session.</description>
        </group>
        <group group_id="B2">
          <title>Hand CCFES</title>
          <description>Uses an electrical stimulator that opens the paretic hand in response to and with an intensity proportional to movement of the contralateral hand.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided CCFES-mediated task practice performed 70 minutes twice a week in the research laboratory.&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 46 min/session.</description>
        </group>
        <group group_id="B3">
          <title>Arm+Hand Cyclic NMES</title>
          <description>Uses an electrical stimulator that delivers stimulation to open the hand and extend the elbow repeatedly with preprogrammed timing and intensity.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided task practice performed 70 minutes twice a week in the research laboratory. (Stimulator not used during these sessions. To ensure that all 3 groups receive an equivalent dose of stimulation, this group has slightly lengthened self-administered hand opening exercise sessions at home.)&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 60 min/session.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="28"/>
            <count group_id="B2" value="28"/>
            <count group_id="B3" value="11"/>
            <count group_id="B4" value="67"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="54" spread="12.6"/>
                    <measurement group_id="B2" value="60" spread="11.5"/>
                    <measurement group_id="B3" value="61" spread="12.5"/>
                    <measurement group_id="B4" value="58" spread="12.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Sex: Female, Male</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="8"/>
                    <measurement group_id="B4" value="24"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="21"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="43"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race/Ethnicity, Customized</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <title>Black or African American</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="22"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>White</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="13"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="9"/>
                    <measurement group_id="B4" value="41"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Other</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Box and Block Test (BBT) Score at 6 Months Post-Treatment</title>
        <description>The BBT counts how many blocks a participant can pick up, move over a barrier, and release in 60 seconds. Higher scores mean a better outcome.</description>
        <time_frame>2 timepoints: prior to treatment, 6 months post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm+Hand CCFES</title>
            <description>Uses an electrical stimulator that opens the paretic hand and extends the paretic elbow in response to and with an intensity proportional to movement of the contralateral arm and hand.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided CCFES-mediated task practice performed 70 minutes twice a week in the research laboratory.&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 46 min/session.</description>
          </group>
          <group group_id="O2">
            <title>Hand CCFES</title>
            <description>Uses an electrical stimulator that opens the paretic hand in response to and with an intensity proportional to movement of the contralateral hand.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided CCFES-mediated task practice performed 70 minutes twice a week in the research laboratory.&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 46 min/session.</description>
          </group>
          <group group_id="O3">
            <title>Arm+Hand Cyclic NMES</title>
            <description>Uses an electrical stimulator that delivers stimulation to open the hand and extend the elbow repeatedly with preprogrammed timing and intensity.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided task practice performed 70 minutes twice a week in the research laboratory. (Stimulator not used during these sessions. To ensure that all 3 groups receive an equivalent dose of stimulation, this group has slightly lengthened self-administered hand opening exercise sessions at home.)&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 60 min/session.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Box and Block Test (BBT) Score at 6 Months Post-Treatment</title>
          <description>The BBT counts how many blocks a participant can pick up, move over a barrier, and release in 60 seconds. Higher scores mean a better outcome.</description>
          <units>blocks</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="13.5" lower_limit="6.4" upper_limit="20.6"/>
                    <measurement group_id="O2" value="12.6" lower_limit="7.4" upper_limit="17.7"/>
                    <measurement group_id="O3" value="9.6" lower_limit="2.6" upper_limit="16.7"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Reachable Workspace (RW) at 6 Months Post-Treatment</title>
        <description>Reachable Workspace (RW) is the area (cm^2) traced out when reaching for a target moving in a circular path just outside the reach of the participant.</description>
        <time_frame>2 timepoints: prior to treatment, 6 months post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm+Hand CCFES</title>
            <description>Uses an electrical stimulator that opens the paretic hand and extends the paretic elbow in response to and with an intensity proportional to movement of the contralateral arm and hand.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided CCFES-mediated task practice performed 70 minutes twice a week in the research laboratory.&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 46 min/session.</description>
          </group>
          <group group_id="O2">
            <title>Hand CCFES</title>
            <description>Uses an electrical stimulator that opens the paretic hand in response to and with an intensity proportional to movement of the contralateral hand.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided CCFES-mediated task practice performed 70 minutes twice a week in the research laboratory.&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 46 min/session.</description>
          </group>
          <group group_id="O3">
            <title>Arm+Hand Cyclic NMES</title>
            <description>Uses an electrical stimulator that delivers stimulation to open the hand and extend the elbow repeatedly with preprogrammed timing and intensity.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided task practice performed 70 minutes twice a week in the research laboratory. (Stimulator not used during these sessions. To ensure that all 3 groups receive an equivalent dose of stimulation, this group has slightly lengthened self-administered hand opening exercise sessions at home.)&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 60 min/session.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Reachable Workspace (RW) at 6 Months Post-Treatment</title>
          <description>Reachable Workspace (RW) is the area (cm^2) traced out when reaching for a target moving in a circular path just outside the reach of the participant.</description>
          <units>squared centimeters</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="430" lower_limit="221" upper_limit="639"/>
                    <measurement group_id="O2" value="166" lower_limit="55" upper_limit="276"/>
                    <measurement group_id="O3" value="152" lower_limit="4" upper_limit="300"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Upper Extremity Fugl-Meyer (UEFM) Score at 6 Months Post-Treatment</title>
        <description>The Upper Extremity Fugl-Meyer (UEFM) is an assessment of motor impairment of the upper limb in which the participant is asked to make specific movements of the arm, forearm, wrist, and hand. Each movement is scored 0, 1, or 2 and the subscores are summed.&#xD;
Min=0; Max=66. Higher scores mean a better outcome.</description>
        <time_frame>2 timepoints: prior to treatment, 6 months post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm+Hand CCFES</title>
            <description>Uses an electrical stimulator that opens the paretic hand and extends the paretic elbow in response to and with an intensity proportional to movement of the contralateral arm and hand.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided CCFES-mediated task practice performed 70 minutes twice a week in the research laboratory.&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 46 min/session.</description>
          </group>
          <group group_id="O2">
            <title>Hand CCFES</title>
            <description>Uses an electrical stimulator that opens the paretic hand in response to and with an intensity proportional to movement of the contralateral hand.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided CCFES-mediated task practice performed 70 minutes twice a week in the research laboratory.&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 46 min/session.</description>
          </group>
          <group group_id="O3">
            <title>Arm+Hand Cyclic NMES</title>
            <description>Uses an electrical stimulator that delivers stimulation to open the hand and extend the elbow repeatedly with preprogrammed timing and intensity.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided task practice performed 70 minutes twice a week in the research laboratory. (Stimulator not used during these sessions. To ensure that all 3 groups receive an equivalent dose of stimulation, this group has slightly lengthened self-administered hand opening exercise sessions at home.)&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 60 min/session.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Upper Extremity Fugl-Meyer (UEFM) Score at 6 Months Post-Treatment</title>
          <description>The Upper Extremity Fugl-Meyer (UEFM) is an assessment of motor impairment of the upper limb in which the participant is asked to make specific movements of the arm, forearm, wrist, and hand. Each movement is scored 0, 1, or 2 and the subscores are summed.&#xD;
Min=0; Max=66. Higher scores mean a better outcome.</description>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="11.0" lower_limit="6.1" upper_limit="16.0"/>
                    <measurement group_id="O2" value="4.4" lower_limit="0.9" upper_limit="7.9"/>
                    <measurement group_id="O3" value="10.7" lower_limit="8.2" upper_limit="13.2"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Stroke Upper Limb Capacity Scale (SULCS) at 6 Months Post-Treatment</title>
        <description>Stroke Upper Limb Capacity Scale (SULCS) is a 10-item test in which participants are given a score of 0 or 1 on their performance of tasks requiring varying degrees of upper limb capacity.&#xD;
Min=0; Max=10. Higher scores mean a better outcome.</description>
        <time_frame>2 timepoints: prior to treatment, 6 months post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm+Hand CCFES</title>
            <description>Uses an electrical stimulator that opens the paretic hand and extends the paretic elbow in response to and with an intensity proportional to movement of the contralateral arm and hand.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided CCFES-mediated task practice performed 70 minutes twice a week in the research laboratory.&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 46 min/session.</description>
          </group>
          <group group_id="O2">
            <title>Hand CCFES</title>
            <description>Uses an electrical stimulator that opens the paretic hand in response to and with an intensity proportional to movement of the contralateral hand.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided CCFES-mediated task practice performed 70 minutes twice a week in the research laboratory.&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 46 min/session.</description>
          </group>
          <group group_id="O3">
            <title>Arm+Hand Cyclic NMES</title>
            <description>Uses an electrical stimulator that delivers stimulation to open the hand and extend the elbow repeatedly with preprogrammed timing and intensity.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided task practice performed 70 minutes twice a week in the research laboratory. (Stimulator not used during these sessions. To ensure that all 3 groups receive an equivalent dose of stimulation, this group has slightly lengthened self-administered hand opening exercise sessions at home.)&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 60 min/session.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Stroke Upper Limb Capacity Scale (SULCS) at 6 Months Post-Treatment</title>
          <description>Stroke Upper Limb Capacity Scale (SULCS) is a 10-item test in which participants are given a score of 0 or 1 on their performance of tasks requiring varying degrees of upper limb capacity.&#xD;
Min=0; Max=10. Higher scores mean a better outcome.</description>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="2.6" lower_limit="1.2" upper_limit="3.9"/>
                    <measurement group_id="O2" value="1.5" lower_limit="0.7" upper_limit="2.4"/>
                    <measurement group_id="O3" value="1.9" lower_limit="1.1" upper_limit="2.8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Arm Motor Abilities Test (AMAT) at 6 Months Post-Treatment</title>
        <description>The Arm Motor Abilities Test (AMAT) is an assessment of the participant's ability to do 9 standardized upper limb tasks. Each task is composed of 1 to 3 component tasks, each of which is rated on an ordinal scale of 0 to 5. The final score is the average of all component task scores across all 9 compound tasks.&#xD;
Min=0; Max=5. Higher scores mean a better outcome.</description>
        <time_frame>2 timepoints: prior to treatment, 6 months post-treatment</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Arm+Hand CCFES</title>
            <description>Uses an electrical stimulator that opens the paretic hand and extends the paretic elbow in response to and with an intensity proportional to movement of the contralateral arm and hand.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided CCFES-mediated task practice performed 70 minutes twice a week in the research laboratory.&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 46 min/session.</description>
          </group>
          <group group_id="O2">
            <title>Hand CCFES</title>
            <description>Uses an electrical stimulator that opens the paretic hand in response to and with an intensity proportional to movement of the contralateral hand.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided CCFES-mediated task practice performed 70 minutes twice a week in the research laboratory.&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 46 min/session.</description>
          </group>
          <group group_id="O3">
            <title>Arm+Hand Cyclic NMES</title>
            <description>Uses an electrical stimulator that delivers stimulation to open the hand and extend the elbow repeatedly with preprogrammed timing and intensity.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided task practice performed 70 minutes twice a week in the research laboratory. (Stimulator not used during these sessions. To ensure that all 3 groups receive an equivalent dose of stimulation, this group has slightly lengthened self-administered hand opening exercise sessions at home.)&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 60 min/session.</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Arm Motor Abilities Test (AMAT) at 6 Months Post-Treatment</title>
          <description>The Arm Motor Abilities Test (AMAT) is an assessment of the participant's ability to do 9 standardized upper limb tasks. Each task is composed of 1 to 3 component tasks, each of which is rated on an ordinal scale of 0 to 5. The final score is the average of all component task scores across all 9 compound tasks.&#xD;
Min=0; Max=5. Higher scores mean a better outcome.</description>
          <units>units on a scale</units>
          <param>Least Squares Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="21"/>
                <count group_id="O2" value="24"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="1.0" lower_limit="0.5" upper_limit="1.6"/>
                    <measurement group_id="O2" value="0.8" lower_limit="0.6" upper_limit="1.1"/>
                    <measurement group_id="O3" value="0.9" lower_limit="0.5" upper_limit="1.4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From enrollment to 6-month post-treatment outcome assessment.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Arm+Hand CCFES</title>
          <description>Uses an electrical stimulator that opens the paretic hand and extends the paretic elbow in response to and with an intensity proportional to movement of the contralateral arm and hand.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided CCFES-mediated task practice performed 70 minutes twice a week in the research laboratory.&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 46 min/session.</description>
        </group>
        <group group_id="E2">
          <title>Hand CCFES</title>
          <description>Uses an electrical stimulator that opens the paretic hand in response to and with an intensity proportional to movement of the contralateral hand.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided CCFES-mediated task practice performed 70 minutes twice a week in the research laboratory.&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 46 min/session.</description>
        </group>
        <group group_id="E3">
          <title>Arm+Hand Cyclic NMES</title>
          <description>Uses an electrical stimulator that delivers stimulation to open the hand and extend the elbow repeatedly with preprogrammed timing and intensity.&#xD;
Electrical stimulator: The 12-week treatment period consists of two components:&#xD;
Therapist-guided task practice performed 70 minutes twice a week in the research laboratory. (Stimulator not used during these sessions. To ensure that all 3 groups receive an equivalent dose of stimulation, this group has slightly lengthened self-administered hand opening exercise sessions at home.)&#xD;
Self-administered hand opening exercise performed 10 sessions per week at home using the device. 60 min/session.</description>
        </group>
      </group_list>
      <serious_events>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, all-cause mortality</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="7" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Shoulder pain related to RW assessment</sub_title>
                <counts group_id="E1" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="2" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Numbness and Tingling in Both Hands</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Abdominal Pain During RW Assessment</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
              <event>
                <sub_title>Transient Discomfort from Stimulation</sub_title>
                <counts group_id="E1" subjects_affected="1" subjects_at_risk="28"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="28"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="11"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Dr. Jayme Knutson</name_or_title>
      <organization>The MetroHealth System</organization>
      <phone>216-957-3557</phone>
      <email>jsk12@case.edu</email>
    </point_of_contact>
  </clinical_results>
</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/NCT01688856
org study id: IRB12-00493
secondary id: R01HD068588
nct id: NCT01688856
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
has dmc: No
Impaired arm and hand function is one of the most disabling and most common consequences of
      stroke. The Investigators have developed Contralaterally Controlled Functional Electrical
      Stimulation (CCFES), an innovative neuromuscular electrical stimulation (NMES) treatment for
      improving the recovery of hand function after stroke. The purpose of this study is to
      maximize the treatment effect of CCFES by adding stimulated elbow extension. The specific
      aims and hypotheses are as follows:

      AIM 1: Estimate the effect of Arm+Hand CCFES on upper limb motor impairment and activity
      limitation.

      Hypothesis 1: Stroke survivors treated with Arm+Hand CCFES have better outcomes on upper limb
      impairment and activity limitation measures than those treated with dose-matched Arm+Hand
      Cyclic NMES.

      AIM 2: Estimate the effect of adding stimulated elbow extension to Hand CCFES.

      Hypothesis 2: Stroke survivors treated with Arm+Hand CCFES will have greater reductions in
      upper limb impairment and activity limitation than those treated with Hand CCFES.

      AIM 3: Describe the relationship between treatment effect and time elapsed between stroke
      onset and start of treatment.

      Hypothesis 3: Patients who start Arm+Hand CCFES sooner after their stroke achieve better
      outcomes.
Loss of arm and hand function is a severely disabling condition that occurs in nearly 75% of
      the estimated 795,000 Americans who have a new or recurrent stroke each year [Roger 2011].
      Upper limb impairment is often characterized by inability to extend the elbow and open the
      hand. The hope of regaining lost motor function after stroke has been fueled in recent years
      by the development of new rehabilitation therapies and devices that are aimed at promoting
      the brain's capacity to reorganize after injury in such a way that restores motor control of
      paretic limbs [Nudo 2001]. The Investigators' long-term objective is to develop stroke
      rehabilitation treatments for the hemiparetic upper limb that are optimized for
      effectiveness, applicability, and deployability.

      The primary objective of this project is to estimate the effect of Arm+Hand Contralaterally
      Controlled Functional Electrical Stimulation (CCFES) in reducing upper limb motor impairment
      and activity limitation in subacute hemiplegia. CCFES is a treatment aimed at improving
      recovery of volitional motor function in stroke survivors [Knutson 2007; Knutson 2009;
      Knutson 2010]. Hand CCFES activates finger and thumb extensors with an intensity of
      electrical stimulation that is proportional to the degree of opening of the contralateral
      unimpaired hand wearing an instrumented glove. Thus, volitional opening of the nonparetic
      hand produces stimulated opening of the paretic hand. The Hand CCFES system enables stroke
      patients to use their impaired hand to practice functional tasks in therapy sessions. CCFES
      incorporates the following features considered to be important to motor recovery and
      promoting neuroplasticity: synchronization of motor intent with motor execution of paretic
      hand opening [Rushton 2003; Kimberley 2004], bilateral symmetric movement [Luft 2004],
      intensive repetitive hand opening exercises [Lang 2009], and the practice of functional tasks
      [Nudo 2003]. In a pilot case series study of patients with chronic (> 6 months) post-stroke
      hemiplegia, all 6 participants experienced some reduction of upper limb motor impairment
      after several weeks of Hand CCFES [Knutson 2007; Knutson 2009]. The results of a Phase I
      randomized clinical trial (RCT) of Hand CCFES in 21 patients with subacute (≤ 6 months)
      hemiplegia suggested that Hand CCFES may be superior to cyclic neuromuscular electrical
      stimulation (NMES) in reducing upper extremity impairment and activity limitation [Knutson
      2011].

      In this study, added to the Hand CCFES treatment is stimulated elbow extension controlled by
      the contralateral elbow. This "next generation" CCFES treatment is called Arm+Hand CCFES.
      Arm+Hand CCFES therapy is intended to strengthen and improve the motor control of the
      proximal upper limb as well as the hand, to improve simultaneous reaching and hand opening, a
      functionally critical movement pattern that is often prevented by paresis and post-stroke
      flexor synergies. The secondary objective of this project is to evaluate the effect of adding
      elbow extensor stimulation to the Hand CCFES treatment.

      Stroke survivors who are ≤ 2 years post-stroke with upper limb hemiplegia will be randomly
      assigned to receive 12 weeks of either Arm+Hand CCFES (stimulates elbow extension and hand
      opening), Hand CCFES (stimulates hand opening), or Arm+Hand Cyclic NMES (stimulates elbow
      extension and hand opening but with pre-set timing and intensity, i.e., not
      intention-driven), plus lab-based therapist-guided task practice. Upper limb impairment and
      activity limitation will be assessed at baseline, 6, 12, 20, 28, and 36 weeks.

      This is the first randomized controlled trial of Arm+Hand CCFES in subacute upper extremity
      hemiplegia. Ultimately, the information learned in this study will serve to accelerate the
      development of a new treatment for reducing post-stroke disability.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Single (Outcomes Assessor)
measure: Change in Box and Block Test (BBT) Score at 6 Months Post-Treatment
time frame: 2 timepoints: prior to treatment, 6 months post-treatment
description: The BBT counts how many blocks a participant can pick up, move over a barrier, and release in 60 seconds. Higher scores mean a better outcome.
measure: Change in Reachable Workspace (RW) at 6 Months Post-Treatment
time frame: 2 timepoints: prior to treatment, 6 months post-treatment
description: Reachable Workspace (RW) is the area (cm^2) traced out when reaching for a target moving in a circular path just outside the reach of the participant.
measure: Change in Upper Extremity Fugl-Meyer (UEFM) Score at 6 Months Post-Treatment
time frame: 2 timepoints: prior to treatment, 6 months post-treatment
description: The Upper Extremity Fugl-Meyer (UEFM) is an assessment of motor impairment of the upper limb in which the participant is asked to make specific movements of the arm, forearm, wrist, and hand. Each movement is scored 0, 1, or 2 and the subscores are summed.
Min=0; Max=66. Higher scores mean a better outcome.
measure: Change in Stroke Upper Limb Capacity Scale (SULCS) at 6 Months Post-Treatment
time frame: 2 timepoints: prior to treatment, 6 months post-treatment
description: Stroke Upper Limb Capacity Scale (SULCS) is a 10-item test in which participants are given a score of 0 or 1 on their performance of tasks requiring varying degrees of upper limb capacity.
Min=0; Max=10. Higher scores mean a better outcome.
measure: Change in Arm Motor Abilities Test (AMAT) at 6 Months Post-Treatment
time frame: 2 timepoints: prior to treatment, 6 months post-treatment
description: The Arm Motor Abilities Test (AMAT) is an assessment of the participant's ability to do 9 standardized upper limb tasks. Each task is composed of 1 to 3 component tasks, each of which is rated on an ordinal scale of 0 to 5. The final score is the average of all component task scores across all 9 compound tasks.
Min=0; Max=5. Higher scores mean a better outcome.
arm group label: Arm+Hand CCFES
arm group type: Experimental
description: Uses an electrical stimulator that opens the paretic hand and extends the paretic elbow in response to and with an intensity proportional to movement of the contralateral arm and hand. The treatment dose will be approximately 2 hrs per day of self-administered stimulation-mediated exercise at home plus 70 min of functional task practice twice a week in the laboratory for 12 weeks.
arm group label: Hand CCFES
arm group type: Experimental
description: Uses an electrical stimulator that opens the paretic hand in response to and with an intensity proportional to movement of the contralateral hand. The treatment dose will be approximately 2 hrs per day of self-administered stimulation-mediated exercise at home plus 70 min of functional task practice twice a week in the laboratory for 12 weeks.
arm group label: Arm+Hand Cyclic NMES
arm group type: Active Comparator
description: Uses an electrical stimulator that delivers stimulation to open the hand and extend the elbow repeatedly with preprogrammed timing and intensity. The treatment dose will be approximately 2 hrs per day of self-administered stimulation-mediated exercise at home plus 70 min of functional task practice twice a week in the laboratory for 12 weeks.
intervention type: Device
intervention name: Electrical Stimulator
description: The 12-week treatment period consists of two components:
Therapist-guided task practice performed 70 minutes twice a week in the research laboratory. If Arm+Hand CCFES or Hand CCFES, the stimulator is used during task practice.
Self-administered muscle stimulation exercise performed 10 sessions per week at home using the device. If Arm+Hand CCFES or Hand CCFES, each session is 46 minutes. If Arm+Hand Cyclic NMES, each session is 60 minutes.
arm group label: Arm+Hand CCFES
arm group label: Arm+Hand Cyclic NMES
arm group label: Hand CCFES
criteria: 
gender: All
minimum age: 21 Years
maximum age: 80 Years
healthy volunteers: No
last name: Jayme S. Knutson, PhD
role: Principal Investigator
affiliation: MetroHealth Medical Center
facility: 
country: United States
url: http://fescenter.org/index.php
description: Cleveland FES Center
citation: Nudo RJ, Plautz EJ, Frost SB. Role of adaptive plasticity in recovery of function after damage to motor cortex. Muscle Nerve. 2001 Aug;24(8):1000-19. doi: 10.1002/mus.1104.
PMID: 11439375
citation: Knutson JS, Harley MY, Hisel TZ, Chae J. Improving hand function in stroke survivors: a pilot study of contralaterally controlled functional electric stimulation in chronic hemiplegia. Arch Phys Med Rehabil. 2007 Apr;88(4):513-20. doi: 10.1016/j.apmr.2007.01.003.
PMID: 17398254
citation: Knutson JS, Hisel TZ, Harley MY, Chae J. A novel functional electrical stimulation treatment for recovery of hand function in hemiplegia: 12-week pilot study. Neurorehabil Neural Repair. 2009 Jan;23(1):17-25. doi: 10.1177/1545968308317577. Epub 2008 Sep 23.
PMID: 18812432
citation: Knutson JS, Chae J. A novel neuromuscular electrical stimulation treatment for recovery of ankle dorsiflexion in chronic hemiplegia: a case series pilot study. Am J Phys Med Rehabil. 2010 Aug;89(8):672-82. doi: 10.1097/PHM.0b013e3181e29bd7.
PMID: 20531158
citation: Kimberley TJ, Lewis SM, Auerbach EJ, Dorsey LL, Lojovich JM, Carey JR. Electrical stimulation driving functional improvements and cortical changes in subjects with stroke. Exp Brain Res. 2004 Feb;154(4):450-60. doi: 10.1007/s00221-003-1695-y. Epub 2003 Nov 15.
PMID: 14618287
citation: Rushton DN. Functional electrical stimulation and rehabilitation--an hypothesis. Med Eng Phys. 2003 Jan;25(1):75-8. doi: 10.1016/s1350-4533(02)00040-1.
PMID: 12485788
citation: Luft AR, McCombe-Waller S, Whitall J, Forrester LW, Macko R, Sorkin JD, Schulz JB, Goldberg AP, Hanley DF. Repetitive bilateral arm training and motor cortex activation in chronic stroke: a randomized controlled trial. JAMA. 2004 Oct 20;292(15):1853-61. doi: 10.1001/jama.292.15.1853. Erratum In: JAMA. 2004 Nov 24;292(20):2470.
PMID: 15494583
citation: Lang CE, Macdonald JR, Reisman DS, Boyd L, Jacobson Kimberley T, Schindler-Ivens SM, Hornby TG, Ross SA, Scheets PL. Observation of amounts of movement practice provided during stroke rehabilitation. Arch Phys Med Rehabil. 2009 Oct;90(10):1692-8. doi: 10.1016/j.apmr.2009.04.005.
PMID: 19801058
citation: Nudo RJ. Adaptive plasticity in motor cortex: implications for rehabilitation after brain injury. J Rehabil Med. 2003 May;(41 Suppl):7-10. doi: 10.1080/16501960310010070.
PMID: 12817650
citation: Knutson JS, Harley MY, Hisel TZ, Hogan SD, Maloney MM, Chae J. Contralaterally controlled functional electrical stimulation for upper extremity hemiplegia: an early-phase randomized clinical trial in subacute stroke patients. Neurorehabil Neural Repair. 2012 Mar-Apr;26(3):239-46. doi: 10.1177/1545968311419301. Epub 2011 Aug 29.
PMID: 21875892
citation: Roger VL, Go AS, Lloyd-Jones DM, Adams RJ, Berry JD, Brown TM, Carnethon MR, Dai S, de Simone G, Ford ES, Fox CS, Fullerton HJ, Gillespie C, Greenlund KJ, Hailpern SM, Heit JA, Ho PM, Howard VJ, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Makuc DM, Marcus GM, Marelli A, Matchar DB, McDermott MM, Meigs JB, Moy CS, Mozaffarian D, Mussolino ME, Nichol G, Paynter NP, Rosamond WD, Sorlie PD, Stafford RS, Turan TN, Turner MB, Wong ND, Wylie-Rosett J; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart disease and stroke statistics--2011 update: a report from the American Heart Association. Circulation. 2011 Feb 1;123(4):e18-e209. doi: 10.1161/CIR.0b013e3182009701. Epub 2010 Dec 15. Erratum In: Circulation. 2011 Feb 15;123(6):e240. Circulation. 2011 Oct 18;124(16):e426.
PMID: 21160056
responsible party type: Principal Investigator
investigator affiliation: MetroHealth Medical Center
investigator full name: Jayme Knutson
investigator title: Assistant Professor, Physical Medicine and Rehabilitation
mesh term: Stroke
mesh term: Hemiplegia
mesh term: Paresis
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 