<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/NCT03010462</url>
  </required_header>
  <id_info>
    <org_study_id>NX103391</org_study_id>
    <nct_id>NCT03010462</nct_id>
  </id_info>
  <brief_title>Electric Field Navigated 1hz Rtms for Post-stroke Motor Recovery Trial</brief_title>
  <acronym>E-FIT</acronym>
  <official_title>A Prospective, Multi-center, Randomized, Sham-controlled Trial to Determine the Therapeutic Effects of Navigation Guided 1 hz Rtms Administered to the Contralesional Hemisphere as Adjuvant to Task-oriented Rehabilitation in Patients With Ischemic Stroke</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Nexstim Ltd</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Nexstim Ltd</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_unapproved_device>Yes</is_unapproved_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      A prospective, multi-center, randomized, sham-controlled, blinded study combining active&#xD;
      Nexstim NBS-guided 1Hz rTMS or sham-rTMS targeting the healthy hemisphere with standardized&#xD;
      task oriented rehabilitation will be conducted in patients with post-stroke motor impairment&#xD;
      of the upper limb. The therapy will be provided for 6 weeks and primary outcome assessed 6&#xD;
      months later.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">March 1, 2017</start_date>
  <completion_date type="Actual">August 15, 2018</completion_date>
  <primary_completion_date type="Actual">August 15, 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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Upper Extremity Fugl-Meyer Score</measure>
    <time_frame>Change from baseline to 6 months after end of treatment.</time_frame>
    <description>Range 0 to 65. HIgher scores indicate better function. Minimal clinically important difference = change of 5 points or more on scale. Outcome measure = proportion of patients in treatment arm gaining at least 5 points on scale between baseline and 6 months after end of treatment.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Upper Extremity Fugl-Meyer Score</measure>
    <time_frame>Change in score from baseline to 6 months after end of treatment</time_frame>
    <description>Range 0-65. HIgher scores indicate better function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Arm-Research Action Test (ARAT)</measure>
    <time_frame>Change in score from baseline to 6 months after end of treatment.</time_frame>
    <description>Range 0 to 57. Higher scores indicate better function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>NIH Stroke Scale (NIHSS)</measure>
    <time_frame>Change in score from baseline to 6 months after end of treatment</time_frame>
    <description>National Institute of Health Stroke Scale - Motor Arm. Range 0 to 4. Lower score indicates better function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Quality of Life Assessment: EQ-5D</measure>
    <time_frame>Change in score from baseline to 6 months after end of treatment</time_frame>
    <description>EuroQoL - EQ-5D score. Range 0 to 100. HIgher numbers indicate better quality of life.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">60</enrollment>
  <condition>Ischemic Stroke</condition>
  <arm_group>
    <arm_group_label>Active</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>Intervention: Device: NBS-guided rTMS + task-oriented rehabilitation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Control</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>Intervention: Device: NBS-guided Sham rTMS + task-oriented rehabilitation</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Nexstim NBS guided active rTMS</intervention_name>
    <description>Nexstim NBS guided active rTMS + standardized task-oriented therapy</description>
    <arm_group_label>Active</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Nexstim NBS guided sham rTMS</intervention_name>
    <description>Nexstim NBS guided sham rTMS + standardized task-oriented therapy</description>
    <arm_group_label>Control</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  ≥ 18 years of age&#xD;
&#xD;
          -  An ischemic stroke suffered 3-12 months prior to the study&#xD;
&#xD;
          -  No other known brain abnormalities by history;&#xD;
&#xD;
          -  A one-sided stroke resulting in upper extremity paresis&#xD;
&#xD;
          -  A Chedoke-McMaster Stroke Assessment arm stage and hand stage of 3-6 for the affected&#xD;
             limb&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Implanted metallic parts of implanted electronic devices, including pacemakers,&#xD;
             defibrillators, or implant medication pump;&#xD;
&#xD;
          -  Pregnant or trying to become pregnant; Lack of pregnancy established in females of&#xD;
             child-bearing potential by a negative urine pregnancy test at screening.&#xD;
&#xD;
          -  Active alcohol abuse, illicit drug use or drug abuse or significant mental illness&#xD;
&#xD;
          -  Patients suffering from depression as measured by a score of &gt;10 on the Patient Health&#xD;
             Questionnaire (PHQ9). For clarity, patients diagnosed with depression which is&#xD;
             controlled with stable anti-depressive medication and in whom PHQ9 is &lt;10 are eligible&#xD;
             to participate in the trial.&#xD;
&#xD;
          -  History of epilepsy, defined as at least two unprovoked seizures occurring greater&#xD;
             than 24 hours apart or diagnosis of an epilepsy syndrome, OR a seizure within the last&#xD;
             12 months.&#xD;
&#xD;
          -  Any condition that would prevent the subject from giving voluntary informed consent;&#xD;
&#xD;
          -  An implanted brain stimulator;&#xD;
&#xD;
          -  Any metal in head with the exception of dental work or any ferromagnetic metal&#xD;
             -elsewhere in the body;&#xD;
&#xD;
          -  Enrolled or plans to enroll in an interventional trial during this study;&#xD;
&#xD;
          -  Scalp wounds or infections;&#xD;
&#xD;
               -  Claustrophobia precluding MRI;&#xD;
&#xD;
          -  A fixed contraction deformity in the affected limb that would prevent normal dexterity&#xD;
             if patient were neurologically intact;&#xD;
&#xD;
          -  Excessive spasticity as indicated by the Modified Ashworth Spasticity (MAS) Scale &gt;2/4&#xD;
             in either elbow flexors, wrist flexors or finger flexors of the affected limb;&#xD;
&#xD;
          -  Previous stroke with residual deficits (TIAs not a reason for exclusion);&#xD;
&#xD;
          -  Premorbid (retrospective) modified Rankin Scale (mRS) score ≥2 of any aetiology;&#xD;
&#xD;
          -  A concurrent progressive neurologic disorder, acute coronary syndrome, severe heart&#xD;
             disease (NYHA Classification &gt; 3), or other major medical condition,&#xD;
&#xD;
          -  Confirmed or suspected lower-limb fracture preventing mobilization, patients requiring&#xD;
             palliative care&#xD;
&#xD;
          -  Patients planning to undergo any other occupational therapy during the 6 week active&#xD;
             treatment period of the trial (see section 5.2 for study schedule) than what is&#xD;
             provided in the study&#xD;
&#xD;
          -  A recent injection of botulinium toxin to the affected upper limb in the last 3&#xD;
             months, or the need of an injection of botulinum toxin anytime during the study period&#xD;
             and follow up.&#xD;
&#xD;
          -  A recent injection of phenol to the affected upper limb in the last 6 months, or the&#xD;
             need of an injection of phenol anytime during the study period and follow up.&#xD;
&#xD;
          -  Ataxia as measured by a score &gt; 1 on item 7 (limb ataxia) of the NIH stroke scale.&#xD;
&#xD;
          -  Severe sensory deficits as measured by a score of 2 on item 8 of the NIH stroke scale.&#xD;
&#xD;
          -  Severe aphasia as measured by a score of &gt; 2 on item 9 (best language) of the NIH&#xD;
             stroke scale.&#xD;
&#xD;
          -  Severe neglect as measured by a score of 2 on item 11 (extinction and inattention) of&#xD;
             the NIH stroke scale.&#xD;
&#xD;
          -  Patients unable to comprehend or follow verbal commands&#xD;
&#xD;
          -  Based on PI's or local physician's assessment patient unable to tolerate the trial&#xD;
             procedure due to medical condition&#xD;
&#xD;
          -  A Mini mental status exam (MMSE) &lt;25.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <location>
    <facility>
      <name>Rancho Los Amigos National Rehabilitation Center</name>
      <address>
        <city>Downey</city>
        <state>California</state>
        <zip>90242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Rehabilitation Institute of Chicago</name>
      <address>
        <city>Chicago</city>
        <state>Illinois</state>
        <zip>60611</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Spaulding Rehabilitation Hospital</name>
      <address>
        <city>Boston</city>
        <state>Massachusetts</state>
        <zip>02129</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Burke Medical Research Institute, Weill Cornell Neurology</name>
      <address>
        <city>White Plains</city>
        <state>New York</state>
        <zip>10605</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>University of Cincinnati</name>
      <address>
        <city>Cincinnati</city>
        <state>Ohio</state>
        <zip>45267</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>March 2021</verification_date>
  <study_first_submitted>January 3, 2017</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 5, 2017</study_first_posted>
  <results_first_submitted>March 29, 2021</results_first_submitted>
  <results_first_submitted_qc>March 29, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">April 26, 2021</results_first_posted>
  <disposition_first_submitted>March 9, 2020</disposition_first_submitted>
  <disposition_first_submitted_qc>March 9, 2020</disposition_first_submitted_qc>
  <disposition_first_posted type="Actual">March 13, 2020</disposition_first_posted>
  <last_update_submitted>March 29, 2021</last_update_submitted>
  <last_update_submitted_qc>March 29, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">April 26, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>Stroke</keyword>
  <keyword>rTMS</keyword>
  <keyword>Motor rehabilitation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <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>August 8, 2018</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/62/NCT03010462/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Active</title>
          <description>Intervention: Device: NBS-guided rTMS + task-oriented rehabilitation&#xD;
Nexstim NBS guided active rTMS: Nexstim NBS guided active rTMS + standardized task-oriented therapy</description>
        </group>
        <group group_id="P2">
          <title>Control</title>
          <description>Intervention: Device: NBS-guided Sham rTMS + task-oriented rehabilitation&#xD;
Nexstim NBS guided sham rTMS: Nexstim NBS guided sham rTMS + standardized task-oriented therapy</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="31"/>
                <participants group_id="P2" count="29"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="28">1 subject withdrew consent before baseline visit. 2 subjects completed treatment but were lost during follow-up</participants>
                <participants group_id="P2" count="28">1 subject withdrew consent prior to baseline visit</participants>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </milestone>
          </milestone_list>
          <drop_withdraw_reason_list>
            <drop_withdraw_reason>
              <title>Withdrawal by Subject</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="1"/>
              </participants_list>
            </drop_withdraw_reason>
          </drop_withdraw_reason_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Active</title>
          <description>Intervention: Device: NBS-guided rTMS + task-oriented rehabilitation&#xD;
Nexstim NBS guided active rTMS: Nexstim NBS guided active rTMS + standardized task-oriented therapy</description>
        </group>
        <group group_id="B2">
          <title>Control</title>
          <description>Intervention: Device: NBS-guided Sham rTMS + task-oriented rehabilitation&#xD;
Nexstim NBS guided sham rTMS: Nexstim NBS guided sham rTMS + standardized task-oriented therapy</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="31"/>
            <count group_id="B2" value="29"/>
            <count group_id="B3" value="60"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="29"/>
                    <count group_id="B3" value="60"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="59.0" spread="9.5"/>
                    <measurement group_id="B2" value="58.0" spread="10.9"/>
                    <measurement group_id="B3" value="58.5" spread="10.2"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="29"/>
                    <count group_id="B3" value="60"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>Female</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="10"/>
                    <measurement group_id="B3" value="18"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="23"/>
                    <measurement group_id="B2" value="19"/>
                    <measurement group_id="B3" value="42"/>
                  </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>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="29"/>
                    <count group_id="B3" value="60"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="6"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="24"/>
                    <measurement group_id="B2" value="20"/>
                    <measurement group_id="B3" value="44"/>
                  </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="1"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Time from stroke</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="31"/>
                    <count group_id="B2" value="29"/>
                    <count group_id="B3" value="60"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <title>3-6 months</title>
                  <measurement_list>
                    <measurement group_id="B1" value="15"/>
                    <measurement group_id="B2" value="12"/>
                    <measurement group_id="B3" value="27"/>
                  </measurement_list>
                </category>
                <category>
                  <title>6-12 months</title>
                  <measurement_list>
                    <measurement group_id="B1" value="16"/>
                    <measurement group_id="B2" value="17"/>
                    <measurement group_id="B3" value="33"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Upper extremity Fugl-Meyer score</title>
          <population>2 subjects ( 1 active, 1 sham withdraw consent prior to analysis of study specific baseline characteristics)</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="30"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="58"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="37.4" spread="12.7"/>
                    <measurement group_id="B2" value="42.2" spread="13.2"/>
                    <measurement group_id="B3" value="39.7" spread="13.1"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Action Research Arm Test</title>
          <population>2 subjects ( 1 active, 1 sham withdraw consent prior to analysis of study specific baseline characteristics)</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="30"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="58"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="28.9" spread="17.7"/>
                    <measurement group_id="B2" value="34.7" spread="16.7"/>
                    <measurement group_id="B3" value="31.7" spread="17.3"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>NIHSS</title>
          <population>2 subjects ( 1 active, 1 sham withdraw consent prior to analysis of study specific baseline characteristics)</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="30"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="58"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="2.23" spread="1.74"/>
                    <measurement group_id="B2" value="1.86" spread="1.88"/>
                    <measurement group_id="B3" value="2.05" spread="1.80"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>EQ-5D</title>
          <population>2 subjects ( 1 active, 1 sham withdraw consent prior to analysis of study specific baseline characteristics)</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <analyzed_list>
                <analyzed>
                  <units>Participants</units>
                  <scope>Class</scope>
                  <count_list>
                    <count group_id="B1" value="30"/>
                    <count group_id="B2" value="28"/>
                    <count group_id="B3" value="58"/>
                  </count_list>
                </analyzed>
              </analyzed_list>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="61.8" spread="19.9"/>
                    <measurement group_id="B2" value="70.1" spread="18.4"/>
                    <measurement group_id="B3" value="65.8" spread="19.5"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Upper Extremity Fugl-Meyer Score</title>
        <description>Range 0 to 65. HIgher scores indicate better function. Minimal clinically important difference = change of 5 points or more on scale. Outcome measure = proportion of patients in treatment arm gaining at least 5 points on scale between baseline and 6 months after end of treatment.</description>
        <time_frame>Change from baseline to 6 months after end of treatment.</time_frame>
        <population>Intent to treat population. All subjects completing the baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Active</title>
            <description>Intervention: Device: NBS-guided rTMS + task-oriented rehabilitation&#xD;
Nexstim NBS guided active rTMS: Nexstim NBS guided active rTMS + standardized task-oriented therapy</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Intervention: Device: NBS-guided Sham rTMS + task-oriented rehabilitation&#xD;
Nexstim NBS guided sham rTMS: Nexstim NBS guided sham rTMS + standardized task-oriented therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Upper Extremity Fugl-Meyer Score</title>
          <description>Range 0 to 65. HIgher scores indicate better function. Minimal clinically important difference = change of 5 points or more on scale. Outcome measure = proportion of patients in treatment arm gaining at least 5 points on scale between baseline and 6 months after end of treatment.</description>
          <population>Intent to treat population. All subjects completing the baseline visit.</population>
          <units>Participants</units>
          <param>Count of Participants</param>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="18"/>
                    <measurement group_id="O2" value="14"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>0.62</p_value>
            <method>Chi-squared, Corrected</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Upper Extremity Fugl-Meyer Score</title>
        <description>Range 0-65. HIgher scores indicate better function.</description>
        <time_frame>Change in score from baseline to 6 months after end of treatment</time_frame>
        <population>Intent to treat population. All enrolled subjects who completed the baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Active</title>
            <description>Intervention: Device: NBS-guided rTMS + task-oriented rehabilitation&#xD;
Nexstim NBS guided active rTMS: Nexstim NBS guided active rTMS + standardized task-oriented therapy</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Intervention: Device: NBS-guided Sham rTMS + task-oriented rehabilitation&#xD;
Nexstim NBS guided sham rTMS: Nexstim NBS guided sham rTMS + standardized task-oriented therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Upper Extremity Fugl-Meyer Score</title>
          <description>Range 0-65. HIgher scores indicate better function.</description>
          <population>Intent to treat population. All enrolled subjects who completed the baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="5.17" spread="8.24"/>
                    <measurement group_id="O2" value="5.00" spread="7.29"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>0.46</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Arm-Research Action Test (ARAT)</title>
        <description>Range 0 to 57. Higher scores indicate better function.</description>
        <time_frame>Change in score from baseline to 6 months after end of treatment.</time_frame>
        <population>Intent to treat population. All subjects completing the baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Active</title>
            <description>Intervention: Device: NBS-guided rTMS + task-oriented rehabilitation&#xD;
Nexstim NBS guided active rTMS: Nexstim NBS guided active rTMS + standardized task-oriented therapy</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Intervention: Device: NBS-guided Sham rTMS + task-oriented rehabilitation&#xD;
Nexstim NBS guided sham rTMS: Nexstim NBS guided sham rTMS + standardized task-oriented therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Arm-Research Action Test (ARAT)</title>
          <description>Range 0 to 57. Higher scores indicate better function.</description>
          <population>Intent to treat population. All subjects completing the baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.93" spread="6.99"/>
                    <measurement group_id="O2" value="5.68" spread="7.96"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>0.54</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>NIH Stroke Scale (NIHSS)</title>
        <description>National Institute of Health Stroke Scale - Motor Arm. Range 0 to 4. Lower score indicates better function.</description>
        <time_frame>Change in score from baseline to 6 months after end of treatment</time_frame>
        <population>Intent to treat. All subject completing the baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Active</title>
            <description>Intervention: Device: NBS-guided rTMS + task-oriented rehabilitation&#xD;
Nexstim NBS guided active rTMS: Nexstim NBS guided active rTMS + standardized task-oriented therapy</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Intervention: Device: NBS-guided Sham rTMS + task-oriented rehabilitation&#xD;
Nexstim NBS guided sham rTMS: Nexstim NBS guided sham rTMS + standardized task-oriented therapy</description>
          </group>
        </group_list>
        <measure>
          <title>NIH Stroke Scale (NIHSS)</title>
          <description>National Institute of Health Stroke Scale - Motor Arm. Range 0 to 4. Lower score indicates better function.</description>
          <population>Intent to treat. All subject completing the baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.62" spread="1.35"/>
                    <measurement group_id="O2" value="-0.50" spread="1.40"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>0.59</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Quality of Life Assessment: EQ-5D</title>
        <description>EuroQoL - EQ-5D score. Range 0 to 100. HIgher numbers indicate better quality of life.</description>
        <time_frame>Change in score from baseline to 6 months after end of treatment</time_frame>
        <population>Intent to treat - all subjects completing the baseline visit.</population>
        <group_list>
          <group group_id="O1">
            <title>Active</title>
            <description>Intervention: Device: NBS-guided rTMS + task-oriented rehabilitation&#xD;
Nexstim NBS guided active rTMS: Nexstim NBS guided active rTMS + standardized task-oriented therapy</description>
          </group>
          <group group_id="O2">
            <title>Control</title>
            <description>Intervention: Device: NBS-guided Sham rTMS + task-oriented rehabilitation&#xD;
Nexstim NBS guided sham rTMS: Nexstim NBS guided sham rTMS + standardized task-oriented therapy</description>
          </group>
        </group_list>
        <measure>
          <title>Quality of Life Assessment: EQ-5D</title>
          <description>EuroQoL - EQ-5D score. Range 0 to 100. HIgher numbers indicate better quality of life.</description>
          <population>Intent to treat - all subjects completing the baseline visit.</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="30"/>
                <count group_id="O2" value="28"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="9.86" spread="21.09"/>
                    <measurement group_id="O2" value="8.96" spread="18.80"/>
                  </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>Superiority</non_inferiority_type>
            <p_value>0.70</p_value>
            <method>Wilcoxon (Mann-Whitney)</method>
          </analysis>
        </analysis_list>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>From baseline until 6 months after end of treatment.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Active</title>
          <description>Intervention: Device: NBS-guided rTMS + task-oriented rehabilitation&#xD;
Nexstim NBS guided active rTMS: Nexstim NBS guided active rTMS + standardized task-oriented therapy</description>
        </group>
        <group group_id="E2">
          <title>Control</title>
          <description>Intervention: Device: NBS-guided Sham rTMS + task-oriented rehabilitation&#xD;
Nexstim NBS guided sham rTMS: Nexstim NBS guided sham rTMS + standardized task-oriented therapy</description>
        </group>
      </group_list>
      <serious_events>
        <default_vocab>MedDRA (10.0)</default_vocab>
        <default_assessment>Non-systematic Assessment</default_assessment>
        <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="28"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="4" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="5" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Cardiac disorders</title>
            <event_list>
              <event>
                <sub_title>Atrial fibrillation</sub_title>
                <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="28"/>
              </event>
              <event>
                <sub_title>Cardiac failure congestive</sub_title>
                <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="28"/>
              </event>
              <event>
                <sub_title>Myocardial infarction</sub_title>
                <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="28"/>
              </event>
              <event>
                <sub_title>Pericardial Effusion</sub_title>
                <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="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Eye disorders</title>
            <event_list>
              <event>
                <sub_title>Diplopia</sub_title>
                <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="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Bacterial infection</sub_title>
                <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="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Seizure</sub_title>
                <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="28"/>
              </event>
              <event>
                <sub_title>Tremor</sub_title>
                <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="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Psychiatric disorders</title>
            <event_list>
              <event>
                <sub_title>Self-injurious ideation</sub_title>
                <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="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Renal and urinary disorders</title>
            <event_list>
              <event>
                <sub_title>Acute Kidney Injury</sub_title>
                <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="28"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</frequency_threshold>
        <default_vocab>MedDRA (10.0)</default_vocab>
        <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="5" subjects_at_risk="30"/>
                <counts group_id="E2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>General disorders</title>
            <event_list>
              <event>
                <sub_title>Fatigue</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Infections and infestations</title>
            <event_list>
              <event>
                <sub_title>Urinary tract infection</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="2" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Musculoskeletal and connective tissue disorders</title>
            <event_list>
              <event>
                <sub_title>Musculoskeletal pain</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="30"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="28"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="4" subjects_affected="3" subjects_at_risk="30"/>
                <counts group_id="E2" events="2" subjects_affected="1" subjects_at_risk="28"/>
              </event>
              <event>
                <sub_title>Dizziness</sub_title>
                <counts group_id="E1" events="0" subjects_affected="0" subjects_at_risk="30"/>
                <counts group_id="E2" events="5" subjects_affected="2" subjects_at_risk="28"/>
              </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>Vice President, Medical Affairs</name_or_title>
      <organization>Nexstim Plc</organization>
      <phone>+358927271710</phone>
      <email>jarmo.laine@nexstim.com</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/NCT03010462
org study id: NX103391
nct id: NCT03010462
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: Yes
is unapproved device: Yes
is us export: No
A prospective, multi-center, randomized, sham-controlled, blinded study combining active
      Nexstim NBS-guided 1Hz rTMS or sham-rTMS targeting the healthy hemisphere with standardized
      task oriented rehabilitation will be conducted in patients with post-stroke motor impairment
      of the upper limb. The therapy will be provided for 6 weeks and primary outcome assessed 6
      months later.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Upper Extremity Fugl-Meyer Score
time frame: Change from baseline to 6 months after end of treatment.
description: Range 0 to 65. HIgher scores indicate better function. Minimal clinically important difference = change of 5 points or more on scale. Outcome measure = proportion of patients in treatment arm gaining at least 5 points on scale between baseline and 6 months after end of treatment.
measure: Upper Extremity Fugl-Meyer Score
time frame: Change in score from baseline to 6 months after end of treatment
description: Range 0-65. HIgher scores indicate better function.
measure: Arm-Research Action Test (ARAT)
time frame: Change in score from baseline to 6 months after end of treatment.
description: Range 0 to 57. Higher scores indicate better function.
measure: NIH Stroke Scale (NIHSS)
time frame: Change in score from baseline to 6 months after end of treatment
description: National Institute of Health Stroke Scale - Motor Arm. Range 0 to 4. Lower score indicates better function.
measure: Quality of Life Assessment: EQ-5D
time frame: Change in score from baseline to 6 months after end of treatment
description: EuroQoL - EQ-5D score. Range 0 to 100. HIgher numbers indicate better quality of life.
arm group label: Active
arm group type: Active Comparator
description: Intervention: Device: NBS-guided rTMS + task-oriented rehabilitation
arm group label: Control
arm group type: Sham Comparator
description: Intervention: Device: NBS-guided Sham rTMS + task-oriented rehabilitation
intervention type: Device
intervention name: Nexstim NBS guided active rTMS
description: Nexstim NBS guided active rTMS + standardized task-oriented therapy
arm group label: Active
intervention type: Device
intervention name: Nexstim NBS guided sham rTMS
description: Nexstim NBS guided sham rTMS + standardized task-oriented therapy
arm group label: Control
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
facility: 
facility: 
facility: 
facility: 
facility: 
country: United States
responsible party type: Sponsor
mesh term: Stroke
mesh term: Ischemic Stroke
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 