<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/NCT01726673</url>
  </required_header>
  <id_info>
    <org_study_id>12-102B</org_study_id>
    <nct_id>NCT01726673</nct_id>
  </id_info>
  <brief_title>Robots Paired With tDCS in Stroke Recovery</brief_title>
  <official_title>Effects of Transcranial Direct Current Stimulation Paired With Robotic Arm Therapy on Recovery of Upper Extremity Motor Function in Stroke Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Northwell Health</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Northwell Health</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      The purpose of this study is to evaluate if multiple therapy sessions of Transcranial Direct&#xD;
      Current Stimulation (tDCS non-invasive brain stimulation) combined with robotic arm therapy&#xD;
      lead to a greater functional recovery in upper limb mobility after stroke than that provided&#xD;
      by robotic arm therapy alone.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">September 2012</start_date>
  <completion_date type="Actual">June 2018</completion_date>
  <primary_completion_date type="Actual">January 2018</primary_completion_date>
  <phase>Phase 2</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>Double (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Median Change in Upper Extremity Fugl Meyer Assessment Score</measure>
    <time_frame>baseline, discharge at 12 weeks (immediately following the intervention), and follow-up at 36 weeks (6 months after the intervention)</time_frame>
    <description>The median change in Upper Extremity Fugl-Meyer Score was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total Upper Extremity Fugl Meyer score is reported, with a range 0-66 points, and with higher values indicating better functional status.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Median Change in WOLF Motor Function Test (WMFT)</measure>
    <time_frame>baseline, discharge at 12 weeks (immediately following the intervention), and follow-up at 36 weeks (6 months after the intervention)</time_frame>
    <description>The median change in performance time for the WOLF motor function test was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total WOLF motor function timed score is reported here in seconds, with a range 0-1800 seconds, and with lower values indicating faster completion of task and better functional status.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Median Change in Motor Power Manual Muscle Test Score for the Upper Extremity (MRC)</measure>
    <time_frame>12 weeks (immediately following the intervention) and 36 weeks (6 months after the intervention)</time_frame>
    <description>The median change in Motor Power Manual Muscle Test Score for the upper extremity was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total Motor Power Manual Muscle Test Score is reported here, with a range 0-100 points, and with higher values indicating better functional status.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">54</enrollment>
  <condition>Stroke</condition>
  <arm_group>
    <arm_group_label>tDCS + robotic arm therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Transcranial Direct Current Stimulation (tDCS) 2mA for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total)</description>
  </arm_group>
  <arm_group>
    <arm_group_label>tDCS sham + robotic arm therapy</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>Transcranial Direct Current Stimulation sham condition (0 mA) for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total)</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial Direct Current Stimulation (tDCS)</intervention_name>
    <arm_group_label>tDCS + robotic arm therapy</arm_group_label>
    <other_name>tDCS</other_name>
    <other_name>Low intensity transcranial DC stimulator</other_name>
    <other_name>Soterix 1x1</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Placebo sham</intervention_name>
    <arm_group_label>tDCS sham + robotic arm therapy</arm_group_label>
    <other_name>tDCS sham</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  18 years of age or older&#xD;
&#xD;
          -  First single focal unilateral lesion with diagnosis verified by brain imaging, which&#xD;
             occurred at least 6 months prior&#xD;
&#xD;
          -  Cognitive function sufficient enough to understand experiments and follow instructions&#xD;
&#xD;
          -  Fugl-Meyer assessment of 7 to 58 out of 66 (neither hemiplegic nor fully recovered&#xD;
             motor function in the muscles of the shoulder, elbow, and wrist)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Botox treatment within 6 weeks of enrollment&#xD;
&#xD;
          -  Fixed contraction of the affected limb&#xD;
&#xD;
          -  Complete flaccid paralysis of the affected limb&#xD;
&#xD;
          -  History of hemorrhagic stroke&#xD;
&#xD;
          -  Ongoing use of CNS active medications&#xD;
&#xD;
          -  Ongoing use of psychoactive medications&#xD;
&#xD;
          -  Presence of additional potential tDCS/TMS risk factors including damaged skin at site&#xD;
             of stimulation, presence of a magnetically/mechanically active implant, metal in the&#xD;
             head, family history of epilepsy, and personal history of seizures&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Bruce T Volpe, MD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Feinstein Institute for Medical Research</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Feinstein Institute for Medical Research</name>
      <address>
        <city>Manhasset</city>
        <state>New York</state>
        <zip>11030</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Edwards DJ, Krebs HI, Rykman A, Zipse J, Thickbroom GW, Mastaglia FL, Pascual-Leone A, Volpe BT. Raised corticomotor excitability of M1 forearm area following anodal tDCS is sustained during robotic wrist therapy in chronic stroke. Restor Neurol Neurosci. 2009;27(3):199-207. doi: 10.3233/RNN-2009-0470.</citation>
    <PMID>19531875</PMID>
  </reference>
  <verification_date>May 2021</verification_date>
  <study_first_submitted>October 26, 2012</study_first_submitted>
  <study_first_submitted_qc>November 14, 2012</study_first_submitted_qc>
  <study_first_posted type="Estimate">November 15, 2012</study_first_posted>
  <results_first_submitted>May 14, 2018</results_first_submitted>
  <results_first_submitted_qc>July 18, 2018</results_first_submitted_qc>
  <results_first_posted type="Actual">August 16, 2018</results_first_posted>
  <last_update_submitted>May 12, 2021</last_update_submitted>
  <last_update_submitted_qc>May 12, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">May 14, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Northwell Health</investigator_affiliation>
    <investigator_full_name>Bruce Volpe</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Stroke</keyword>
  <keyword>Cerebrovascular Accident</keyword>
  <keyword>Cerebral Stroke</keyword>
  <keyword>CVA</keyword>
  <keyword>Robotic therapy</keyword>
  <keyword>Upper extremity recovery</keyword>
  <keyword>tDCS</keyword>
  <keyword>Non-invasive brain stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</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>January 26, 2016</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/73/NCT01726673/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Subjects were randomized to receive 36 sessions of either active tDCS immediately followed by robotic arm therapy or sham tDCS immediately followed by robotic arm therapy.</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>tDCS + Robotic Arm Therapy</title>
          <description>Transcranial Direct Current Stimulation (tDCS) 2mA for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total)&#xD;
Transcranial Direct Current Stimulation (tDCS)</description>
        </group>
        <group group_id="P2">
          <title>tDCS Sham + Robotic Arm Therapy</title>
          <description>Transcranial Direct Current Stimulation sham condition (0 mA) for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total).&#xD;
Placebo sham</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="30"/>
                <participants group_id="P2" count="24"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="24"/>
                <participants group_id="P2" count="21"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="6"/>
                <participants group_id="P2" count="3"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>tDCS + Robotic Arm Therapy</title>
          <description>Transcranial Direct Current Stimulation (tDCS) 2mA for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total)&#xD;
Transcranial Direct Current Stimulation (tDCS)</description>
        </group>
        <group group_id="B2">
          <title>tDCS Sham + Robotic Arm Therapy</title>
          <description>Transcranial Direct Current Stimulation sham condition (0 mA) for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total)&#xD;
Placebo sham</description>
        </group>
        <group group_id="B3">
          <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="30"/>
            <count group_id="B2" value="24"/>
            <count group_id="B3" value="54"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="30"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="10"/>
                    <measurement group_id="B2" value="14"/>
                    <measurement group_id="B3" value="24"/>
                  </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="11"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="19"/>
                    <measurement group_id="B2" value="15"/>
                    <measurement group_id="B3" value="34"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="3"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Native Hawaiian or Other Pacific Islander</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="3"/>
                    <measurement group_id="B3" value="10"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="20"/>
                    <measurement group_id="B2" value="13"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Median Change in Upper Extremity Fugl Meyer Assessment Score</title>
        <description>The median change in Upper Extremity Fugl-Meyer Score was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total Upper Extremity Fugl Meyer score is reported, with a range 0-66 points, and with higher values indicating better functional status.</description>
        <time_frame>baseline, discharge at 12 weeks (immediately following the intervention), and follow-up at 36 weeks (6 months after the intervention)</time_frame>
        <population>45 patients completed 36 sessions (3x/week for 12 weeks) of robotic arm training + sham or active tDCS, and 6 month follow-up at 36 weeks. These 45 participants were consequently included in the efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>tDCS + Robotic Arm Therapy</title>
            <description>Active Transcranial Direct Current Stimulation (tDCS) 2mA for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total)&#xD;
Transcranial Direct Current Stimulation (tDCS)</description>
          </group>
          <group group_id="O2">
            <title>tDCS Sham + Robotic Arm Therapy</title>
            <description>Transcranial Direct Current Stimulation sham condition (0 mA) for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total).&#xD;
Placebo sham</description>
          </group>
        </group_list>
        <measure>
          <title>Median Change in Upper Extremity Fugl Meyer Assessment Score</title>
          <description>The median change in Upper Extremity Fugl-Meyer Score was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total Upper Extremity Fugl Meyer score is reported, with a range 0-66 points, and with higher values indicating better functional status.</description>
          <population>45 patients completed 36 sessions (3x/week for 12 weeks) of robotic arm training + sham or active tDCS, and 6 month follow-up at 36 weeks. These 45 participants were consequently included in the efficacy analysis.</population>
          <units>scores on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Median change from baseline to discharge at 12 wks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.5" lower_limit="3" upper_limit="8"/>
                    <measurement group_id="O2" value="6.0" lower_limit="4" upper_limit="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Median change from baseline to 6 month follow-up</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4" lower_limit="2" upper_limit="7"/>
                    <measurement group_id="O2" value="6" lower_limit="4" upper_limit="7.25"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Statistical analysis of median change from baseline to DC immediately following 12 weeks of training was assessed with the upper extremity fugl meyer score in the active vs. sham tDCS conditions. Null hypothesis is that there is no difference in median change in upper extremity fugl meyer score between the active and sham tDCS conditions. A significance level of 0.05 was used (two-tailed).</non_inferiority_desc>
            <p_value>0.256</p_value>
            <p_value_desc>The Mann-Whitney U test was performed to compare median change in upper extremity fugl meyer score from baseline to 12 weeks (discharge) across two separate study conditions (active vs. sham tDCS).</p_value_desc>
            <method>Mann-Whitney U test</method>
            <param_type>U value</param_type>
            <param_value>302</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Statistical analysis of median change from baseline to week 36 (6 month follow-up) was assessed with upper extremity fugl meyer score for the active vs. sham tDCS conditions. Null hypothesis is that there is no difference in median change in upper extremity fugl meyer score between the active and sham tDCS conditions. A significance level of 0.05 was used (two-tailed).</non_inferiority_desc>
            <p_value>0.222</p_value>
            <p_value_desc>The Mann-Whitney U test was performed to compare median change in upper extremity fugl meyer score from baseline to 36 weeks (follow-up) across two separate study conditions (active vs. sham tDCS).</p_value_desc>
            <method>Mann-Whitney U test</method>
            <param_type>U value</param_type>
            <param_value>222</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Change in WOLF Motor Function Test (WMFT)</title>
        <description>The median change in performance time for the WOLF motor function test was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total WOLF motor function timed score is reported here in seconds, with a range 0-1800 seconds, and with lower values indicating faster completion of task and better functional status.</description>
        <time_frame>baseline, discharge at 12 weeks (immediately following the intervention), and follow-up at 36 weeks (6 months after the intervention)</time_frame>
        <population>45 patients completed 36 sessions (3x/week for 12 weeks) of robotic arm training + sham or active tDCS, and 6 month follow-up at 36 weeks. These 45 participants were consequently included in the efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>tDCS + Robotic Arm Therapy</title>
            <description>Active Transcranial Direct Current Stimulation (tDCS) 2mA for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total)&#xD;
Transcranial Direct Current Stimulation (tDCS)</description>
          </group>
          <group group_id="O2">
            <title>tDCS Sham + Robotic Arm Therapy</title>
            <description>Transcranial Direct Current Stimulation sham condition (0 mA) for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total).&#xD;
Placebo sham</description>
          </group>
        </group_list>
        <measure>
          <title>Median Change in WOLF Motor Function Test (WMFT)</title>
          <description>The median change in performance time for the WOLF motor function test was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total WOLF motor function timed score is reported here in seconds, with a range 0-1800 seconds, and with lower values indicating faster completion of task and better functional status.</description>
          <population>45 patients completed 36 sessions (3x/week for 12 weeks) of robotic arm training + sham or active tDCS, and 6 month follow-up at 36 weeks. These 45 participants were consequently included in the efficacy analysis.</population>
          <units>seconds</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Median change from baseline to discharge at 12 wks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-34" lower_limit="-235.25" upper_limit="0"/>
                    <measurement group_id="O2" value="-19" lower_limit="-157" upper_limit="-1.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Median change from baseline to 6 month follow-up</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-103" lower_limit="-245.5" upper_limit="-5"/>
                    <measurement group_id="O2" value="-81.5" lower_limit="-260.5" upper_limit="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Statistical analysis of median change from baseline to DC immediately following 12 weeks of training was assessed with the WOLF Motor Function test time score (out of 1800 seconds) in the active vs. sham tDCS conditions. Null hypothesis is that there is no difference in median change in WMFT time score between the active and sham tDCS conditions. A significance level of 0.05 was used (two-tailed).</non_inferiority_desc>
            <p_value>1.0</p_value>
            <p_value_desc>The Mann-Whitney U test was performed to compare median change in the WMFT time score from baseline to 12 weeks (discharge) across two separate study conditions (active vs. sham tDCS).</p_value_desc>
            <method>Mann-Whitney U Test</method>
            <param_type>U Value</param_type>
            <param_value>251.5</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Statistical analysis of median change from baseline to week 36 (6 month follow-up) was assessed with the WOLF Motor Function test time score (out of 1800 seconds) in the active vs. sham tDCS conditions. Null hypothesis is that there is no difference in median change in WMFT time score between the active and sham tDCS conditions. A significance level of 0.05 was used (two-tailed).</non_inferiority_desc>
            <p_value>0.592</p_value>
            <p_value_desc>The Mann-Whitney U test was performed to compare median change in the WMFT time score from baseline to 36 weeks ( 6 month follow-up) across two separate study conditions (active vs. sham tDCS).</p_value_desc>
            <method>Mann-Whitney U Test</method>
            <param_type>U value</param_type>
            <param_value>208.5</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Median Change in Motor Power Manual Muscle Test Score for the Upper Extremity (MRC)</title>
        <description>The median change in Motor Power Manual Muscle Test Score for the upper extremity was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total Motor Power Manual Muscle Test Score is reported here, with a range 0-100 points, and with higher values indicating better functional status.</description>
        <time_frame>12 weeks (immediately following the intervention) and 36 weeks (6 months after the intervention)</time_frame>
        <population>45 patients completed 36 sessions (3x/week for 12 weeks) of robotic arm training + sham or active tDCS, and 6 month follow-up at 36 weeks. These 45 participants were consequently included in the efficacy analysis.</population>
        <group_list>
          <group group_id="O1">
            <title>tDCS + Robotic Arm Therapy</title>
            <description>Active Transcranial Direct Current Stimulation (tDCS) 2mA for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total)&#xD;
Transcranial Direct Current Stimulation (tDCS)</description>
          </group>
          <group group_id="O2">
            <title>tDCS Sham + Robotic Arm Therapy</title>
            <description>Transcranial Direct Current Stimulation sham condition (0 mA) for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total).&#xD;
Placebo sham</description>
          </group>
        </group_list>
        <measure>
          <title>Median Change in Motor Power Manual Muscle Test Score for the Upper Extremity (MRC)</title>
          <description>The median change in Motor Power Manual Muscle Test Score for the upper extremity was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total Motor Power Manual Muscle Test Score is reported here, with a range 0-100 points, and with higher values indicating better functional status.</description>
          <population>45 patients completed 36 sessions (3x/week for 12 weeks) of robotic arm training + sham or active tDCS, and 6 month follow-up at 36 weeks. These 45 participants were consequently included in the efficacy analysis.</population>
          <units>scores on a scale</units>
          <param>Median</param>
          <dispersion>Inter-Quartile Range</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="24"/>
                <count group_id="O2" value="21"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <title>Median change from baseline to discharge at 12 wks</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="7" lower_limit="4" upper_limit="9.5"/>
                    <measurement group_id="O2" value="7" lower_limit="5" upper_limit="8"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
            <class>
              <title>Median change from baseline to 6 month follow-up</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="6" lower_limit="3" upper_limit="11.25"/>
                    <measurement group_id="O2" value="6" lower_limit="4" upper_limit="9"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <analysis_list>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Statistical analysis of median change from baseline to DC immediately following 12 weeks of training was assessed with the Motor Power Manual Muscle Test Score for the upper extremity (out of 100 points) in the active vs. sham tDCS conditions. Null hypothesis is that there is no difference in median change in MRC score between the active and sham tDCS conditions. A significance level of 0.05 was used (two-tailed).</non_inferiority_desc>
            <p_value>0.680</p_value>
            <p_value_desc>The Mann-Whitney U test was performed to compare median change in the MRC score from baseline to 12 weeks (discharge) across two separate study conditions (active vs. sham tDCS).</p_value_desc>
            <method>Mann-Whitney U test</method>
            <param_type>U value</param_type>
            <param_value>270.5</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
          <analysis>
            <group_id_list>
              <group_id>O1</group_id>
              <group_id>O2</group_id>
            </group_id_list>
            <non_inferiority_type>Equivalence</non_inferiority_type>
            <non_inferiority_desc>Statistical analysis of median change from baseline to week 36 (6 month FU) was assessed with the Motor Power Manual Muscle Test Score for the upper extremity (out of 100 points) in the active vs. sham tDCS conditions. Null hypothesis is that there is no difference in median change in MRC score between the active and sham tDCS conditions. A significance level of 0.05 was used (two-tailed).</non_inferiority_desc>
            <p_value>0.837</p_value>
            <p_value_desc>The Mann-Whitney U test was performed to compare median change in the MRC score from baseline to 6 month FU across two separate study conditions (active vs. sham tDCS).</p_value_desc>
            <method>Mann-Whitney U Test</method>
            <param_type>U value</param_type>
            <param_value>187.5</param_value>
            <ci_n_sides>2-Sided</ci_n_sides>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Patients were followed for a total of 36 weeks, including the 12 weeks of the study intervention, and the 6 month follow-up period.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>tDCS + Robotic Arm Therapy</title>
          <description>Active Transcranial Direct Current Stimulation (tDCS) 2mA for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total)&#xD;
Transcranial Direct Current Stimulation (tDCS)</description>
        </group>
        <group group_id="E2">
          <title>tDCS Sham + Robotic Arm Therapy</title>
          <description>Transcranial Direct Current Stimulation sham condition (0 mA) for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total).&#xD;
Placebo sham</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="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="24"/>
              </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="2" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>back pain flair up</sub_title>
                <description>Subject developed flair up of lower back pain as a result of compromised gait pattern after stroke and consequently had to drop out of the study.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Myasthenia Gravis</sub_title>
                <description>Subject developed spontaneous eye pstosis at home and was diagnosed with Myasthenia Gravis by treating physician, unrelated to study intervention.</description>
                <counts group_id="E1" events="1" subjects_affected="1" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="24"/>
              </event>
              <event>
                <sub_title>seizure</sub_title>
                <assessment>Systematic Assessment</assessment>
                <description>Subject from the sham condition experienced a seizure at home greater than 48 hrs after stimulation, and seizure was determined to be unrelated to study intervention by subject's treating neurologist. Subject was withdrawn from study.</description>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="1" subjects_affected="1" subjects_at_risk="24"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>Principal Investigators are NOT 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>Johanna Chang, Senior Research Coordinator</name_or_title>
      <organization>Feinstein Institute for Medical Research at Northwell Health</organization>
      <phone>(516) 562-3646</phone>
      <email>jchang14@northwell.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/NCT01726673
org study id: 12-102B
nct id: NCT01726673
lead sponsor: 
has dmc: No
The purpose of this study is to evaluate if multiple therapy sessions of Transcranial Direct
      Current Stimulation (tDCS non-invasive brain stimulation) combined with robotic arm therapy
      lead to a greater functional recovery in upper limb mobility after stroke than that provided
      by robotic arm therapy alone.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Median Change in Upper Extremity Fugl Meyer Assessment Score
time frame: baseline, discharge at 12 weeks (immediately following the intervention), and follow-up at 36 weeks (6 months after the intervention)
description: The median change in Upper Extremity Fugl-Meyer Score was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total Upper Extremity Fugl Meyer score is reported, with a range 0-66 points, and with higher values indicating better functional status.
measure: Median Change in WOLF Motor Function Test (WMFT)
time frame: baseline, discharge at 12 weeks (immediately following the intervention), and follow-up at 36 weeks (6 months after the intervention)
description: The median change in performance time for the WOLF motor function test was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total WOLF motor function timed score is reported here in seconds, with a range 0-1800 seconds, and with lower values indicating faster completion of task and better functional status.
measure: Median Change in Motor Power Manual Muscle Test Score for the Upper Extremity (MRC)
time frame: 12 weeks (immediately following the intervention) and 36 weeks (6 months after the intervention)
description: The median change in Motor Power Manual Muscle Test Score for the upper extremity was calculated from baseline to discharge at 12 weeks (immediately following the intervention) and again at 36 weeks (6 months follow-up from the intervention) in each training condition (sham tDCS + robotics arm training vs. active tDCS + robotic arm training). The total Motor Power Manual Muscle Test Score is reported here, with a range 0-100 points, and with higher values indicating better functional status.
arm group label: tDCS + robotic arm therapy
arm group type: Experimental
description: Transcranial Direct Current Stimulation (tDCS) 2mA for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total)
arm group label: tDCS sham + robotic arm therapy
arm group type: Placebo Comparator
description: Transcranial Direct Current Stimulation sham condition (0 mA) for 20 minutes over the primary motor cortex (M1) in the affected hemisphere immediately followed by robotic arm therapy for 60 minutes, 3x per week for 12 weeks (36 sessions total)
intervention type: Device
intervention name: Transcranial Direct Current Stimulation (tDCS)
arm group label: tDCS + robotic arm therapy
other name: tDCS
other name: Low intensity transcranial DC stimulator
other name: Soterix 1x1
intervention type: Device
intervention name: Placebo sham
arm group label: tDCS sham + robotic arm therapy
other name: tDCS sham
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Bruce T Volpe, MD
role: Principal Investigator
affiliation: Feinstein Institute for Medical Research
facility: 
country: United States
citation: Edwards DJ, Krebs HI, Rykman A, Zipse J, Thickbroom GW, Mastaglia FL, Pascual-Leone A, Volpe BT. Raised corticomotor excitability of M1 forearm area following anodal tDCS is sustained during robotic wrist therapy in chronic stroke. Restor Neurol Neurosci. 2009;27(3):199-207. doi: 10.3233/RNN-2009-0470.
PMID: 19531875
responsible party type: Principal Investigator
investigator affiliation: Northwell Health
investigator full name: Bruce Volpe
investigator title: Principal Investigator
mesh term: Stroke
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 