<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/NCT02208466</url>
  </required_header>
  <id_info>
    <org_study_id>2014P001046</org_study_id>
    <nct_id>NCT02208466</nct_id>
  </id_info>
  <brief_title>Effects rTMS Combined With Fluoxetine on Motor Recovery in Stroke Patients</brief_title>
  <official_title>Effects of Contralesional Repetitive Magnetic Stimulation Combined With Fluoxetine on Motor Recovery in Acute Stroke Patients</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Spaulding Rehabilitation Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Spaulding Rehabilitation Hospital</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      In this study investigator's aim to assess the effect of a type of non-invasive brain&#xD;
      stimulation technique called repetitive transcranial magnetic stimulation (rTMS) in&#xD;
      conjunction with fluoxetine on motor recovery after stroke.&#xD;
    </textblock>
  </brief_summary>
  <overall_status>Completed</overall_status>
  <start_date>September 2014</start_date>
  <completion_date type="Actual">June 25, 2019</completion_date>
  <primary_completion_date type="Actual">June 25, 2019</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>Triple (Participant, Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in Motor Function (Jebsen-Taylor Task)</measure>
    <time_frame>baseline and 90 days</time_frame>
    <description>Jebsen Taylor Hand Function Test: measures hand function in real-life activities, by evaluating the time required to perform 7 different tasks. We used the non-constrained hand for the assessments. The sum of the different tasks was used for the analysis.&#xD;
Calculation details: value at 9 months minus value at baseline, change in seconds (adjusted mean difference).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in Fugl-Meyer Assessment (FMA) Scale</measure>
    <time_frame>baseline and 90 days</time_frame>
    <description>The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation, and joint functioning in patients with post-stroke hemiplegia. We used the upper limb motor function subscale: minimum values= 0 ; maximum values= 66. Higher scores mean a better outcome. Changes from baseline to 90 days (value at 90 days minus value at baseline).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Changes in Cortical Excitability Measures</measure>
    <time_frame>Baseline and 90 days</time_frame>
    <description>We will measure cortical excitability using single-pulsed transcranial magnetic stimulation (TMS) before and after stimulation at three different time-points. Changes from baseline to 90 days (value at 90 days minus value at baseline).</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Actual">44</enrollment>
  <condition>Stroke</condition>
  <condition>Motor Function</condition>
  <arm_group>
    <arm_group_label>Active rTMS/active fluoxetine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm will undergo 10 daily sessions over 15 days of active low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of active low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham rTMS/active fluoxetine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham rTMS/placebo fluoxetine</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of placebo fluoxetine by mouth daily.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Active Repetitive Transcranial Magnetic Stimulation (rTMS)</intervention_name>
    <description>Subjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.</description>
    <arm_group_label>Active rTMS/active fluoxetine</arm_group_label>
    <other_name>magnetic stimulation, Magstim</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Fluoxetine</intervention_name>
    <description>Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.</description>
    <arm_group_label>Active rTMS/active fluoxetine</arm_group_label>
    <arm_group_label>Sham rTMS/active fluoxetine</arm_group_label>
    <other_name>Prozac, Sarafem, Ladose, Fontex</other_name>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Sham repetitive transcranial magnetic stimulation (rTMS)</intervention_name>
    <description>Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.</description>
    <arm_group_label>Sham rTMS/active fluoxetine</arm_group_label>
    <arm_group_label>Sham rTMS/placebo fluoxetine</arm_group_label>
    <other_name>Magstim, magnetic stimulation</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Placebo Fluoxetine</intervention_name>
    <description>Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days.</description>
    <arm_group_label>Sham rTMS/placebo fluoxetine</arm_group_label>
    <other_name>Prozac, Sarafem, Ladose, Fontex</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Ischemic infarction within the past 2 years post event that has caused hemiparesis or&#xD;
             hemiplegia, as self-reported and/or confirmed by medical record.&#xD;
&#xD;
          -  Older than 18 years old.&#xD;
&#xD;
          -  Upper extremity weakness defined as a score of &gt;11 and ≤56 on the arm motor Fugl-Mayer&#xD;
             motor scale.&#xD;
&#xD;
          -  Minimal pre-stroke disability defined as a score of &lt;3 in the Modified Rankin Scale.&#xD;
&#xD;
          -  Subjects need to be able to follow directions and participate in 2 hours of testing&#xD;
             with short breaks.&#xD;
&#xD;
          -  Subjects need to be able to provide informed consent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Any substantial decrease in alertness, language reception, or attention that might&#xD;
             interfere with understanding instruction for motor testing&#xD;
&#xD;
          -  Excessive pain in any joint of the paretic extremity (not applicable to severe stroke&#xD;
             subjects), as self reported&#xD;
&#xD;
          -  Contraindications to single pulse TMS (will be used to measure cortical excitability)&#xD;
             such as: history of seizures, unexplained loss of consciousness, any metal implants in&#xD;
             the head, frequent or severe headaches or neck pain, any other electronic implanted&#xD;
             medical devices such as pacemakers, defibrillators, or implant medication pump.&#xD;
&#xD;
          -  Patients who have taken fluoxetine in the past 5 weeks.&#xD;
&#xD;
          -  Patients taking any other SSRI at the time of enrollment or in the previous month.&#xD;
&#xD;
          -  Patients taking any other medication likely to have adverse interaction with SSRIs&#xD;
             (all the medications the patient is taking will be carefully reviewed, as noted below&#xD;
             in &quot;Monitoring of important drug interactions&quot;).&#xD;
&#xD;
          -  Active depression on admission to SRH defined by a score of 24 or higher in the&#xD;
             Hamilton Depression Rating Scale (HAM-D)&#xD;
&#xD;
          -  Concurrent medical condition likely to worsen patient's functional status in the next&#xD;
             6 months such as: cancer, terminal heart, kidney or liver disease, as self-reported&#xD;
             and/or confirmed by medical record.&#xD;
&#xD;
          -  Pregnancy.&#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>Felipe Fregni, MD PhD MPH</last_name>
    <role>Principal Investigator</role>
    <affiliation>Spaulding Rehabilitation Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Spaulding Rehabilitation Hospital</name>
      <address>
        <city>Charlestown</city>
        <state>Massachusetts</state>
        <zip>02129</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>February 2021</verification_date>
  <study_first_submitted>July 28, 2014</study_first_submitted>
  <study_first_submitted_qc>August 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">August 5, 2014</study_first_posted>
  <results_first_submitted>November 25, 2020</results_first_submitted>
  <results_first_submitted_qc>February 2, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">February 21, 2021</results_first_posted>
  <last_update_submitted>February 2, 2021</last_update_submitted>
  <last_update_submitted_qc>February 2, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">February 21, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Spaulding Rehabilitation Hospital</investigator_affiliation>
    <investigator_full_name>Felipe Fregni</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>repetitive transcranial magnetic stimulation</keyword>
  <keyword>rTMS</keyword>
  <keyword>TMS</keyword>
  <keyword>fluoxetine</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
  </condition_browse>
  <intervention_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Fluoxetine</mesh_term>
  </intervention_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>August 10, 2017</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/66/NCT02208466/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <pre_assignment_details>Please note that from the 44 subjects enrolled, only 27 started (were randomized) as 17 subjects screened out during confirmation of eligibility after signing the consent form (some of the criteria could only be checked after consent).</pre_assignment_details>
      <group_list>
        <group group_id="P1">
          <title>Active rTMS/Active Fluoxetine</title>
          <description>Subjects in this arm will undergo 10 daily sessions over 15 days of active low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of active low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.&#xD;
Active Repetitive Transcranial Magnetic Stimulation (rTMS): Subjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.&#xD;
Fluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.</description>
        </group>
        <group group_id="P2">
          <title>Sham rTMS/Active Fluoxetine</title>
          <description>Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.&#xD;
Fluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.&#xD;
Sham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.</description>
        </group>
        <group group_id="P3">
          <title>Sham rTMS/Placebo Fluoxetine</title>
          <description>Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of placebo fluoxetine by mouth daily.&#xD;
Sham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.&#xD;
Placebo Fluoxetine: Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="9"/>
                <participants group_id="P2" count="10"/>
                <participants group_id="P3" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>NOT COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="0"/>
                <participants group_id="P2" count="0"/>
                <participants group_id="P3" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Active rTMS/Active Fluoxetine</title>
          <description>Subjects in this arm will undergo 10 daily sessions over 15 days of active low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of active low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.&#xD;
Active Repetitive Transcranial Magnetic Stimulation (rTMS): Subjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.&#xD;
Fluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.</description>
        </group>
        <group group_id="B2">
          <title>Sham rTMS/Active Fluoxetine</title>
          <description>Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.&#xD;
Fluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.&#xD;
Sham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.</description>
        </group>
        <group group_id="B3">
          <title>Sham rTMS/Placebo Fluoxetine</title>
          <description>Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of placebo fluoxetine by mouth daily.&#xD;
Sham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.&#xD;
Placebo Fluoxetine: Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days.</description>
        </group>
        <group group_id="B4">
          <title>Total</title>
          <description>Total of all reporting groups</description>
        </group>
      </group_list>
      <analyzed_list>
        <analyzed>
          <units>Participants</units>
          <scope>Overall</scope>
          <count_list>
            <count group_id="B1" value="9"/>
            <count group_id="B2" value="10"/>
            <count group_id="B3" value="8"/>
            <count group_id="B4" value="27"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>years</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="57.22" spread="9.39"/>
                    <measurement group_id="B2" value="50.5" spread="16.57"/>
                    <measurement group_id="B3" value="57.38" spread="9.96"/>
                    <measurement group_id="B4" value="55.03" spread="11.97"/>
                  </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="4"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="2"/>
                    <measurement group_id="B4" value="11"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="5"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="6"/>
                    <measurement group_id="B4" value="16"/>
                  </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 group_id="B4" 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 group_id="B4" 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 group_id="B4" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Black or African American</title>
                  <measurement_list>
                    <measurement group_id="B1" value="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="3"/>
                    <measurement group_id="B4" value="5"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="8"/>
                    <measurement group_id="B2" value="9"/>
                    <measurement group_id="B3" value="5"/>
                    <measurement group_id="B4" value="22"/>
                  </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 group_id="B4" 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="0"/>
                    <measurement group_id="B3" value="0"/>
                    <measurement group_id="B4" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Changes in Motor Function (Jebsen-Taylor Task)</title>
        <description>Jebsen Taylor Hand Function Test: measures hand function in real-life activities, by evaluating the time required to perform 7 different tasks. We used the non-constrained hand for the assessments. The sum of the different tasks was used for the analysis.&#xD;
Calculation details: value at 9 months minus value at baseline, change in seconds (adjusted mean difference).</description>
        <time_frame>baseline and 90 days</time_frame>
        <population>Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments</population>
        <group_list>
          <group group_id="O1">
            <title>Active rTMS/Active Fluoxetine</title>
            <description>Subjects in this arm will undergo 10 daily sessions over 15 days of active low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of active low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.&#xD;
Active Repetitive Transcranial Magnetic Stimulation (rTMS): Subjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.&#xD;
Fluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.</description>
          </group>
          <group group_id="O2">
            <title>Sham rTMS/Active Fluoxetine</title>
            <description>Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.&#xD;
Fluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.&#xD;
Sham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.</description>
          </group>
          <group group_id="O3">
            <title>Sham rTMS/Placebo Fluoxetine</title>
            <description>Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of placebo fluoxetine by mouth daily.&#xD;
Sham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.&#xD;
Placebo Fluoxetine: Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Motor Function (Jebsen-Taylor Task)</title>
          <description>Jebsen Taylor Hand Function Test: measures hand function in real-life activities, by evaluating the time required to perform 7 different tasks. We used the non-constrained hand for the assessments. The sum of the different tasks was used for the analysis.&#xD;
Calculation details: value at 9 months minus value at baseline, change in seconds (adjusted mean difference).</description>
          <population>Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments</population>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-214.33" lower_limit="-289.32" upper_limit="-139.35"/>
                    <measurement group_id="O2" value="-50.16" lower_limit="-110.56" upper_limit="-10.24"/>
                    <measurement group_id="O3" value="-117.98" lower_limit="-197.39" upper_limit="-38.58"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Changes in Fugl-Meyer Assessment (FMA) Scale</title>
        <description>The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation, and joint functioning in patients with post-stroke hemiplegia. We used the upper limb motor function subscale: minimum values= 0 ; maximum values= 66. Higher scores mean a better outcome. Changes from baseline to 90 days (value at 90 days minus value at baseline).</description>
        <time_frame>baseline and 90 days</time_frame>
        <population>Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments</population>
        <group_list>
          <group group_id="O1">
            <title>Active rTMS/Active Fluoxetine</title>
            <description>Subjects in this arm will undergo 10 daily sessions over 15 days of active low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of active low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.&#xD;
Active Repetitive Transcranial Magnetic Stimulation (rTMS): Subjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.&#xD;
Fluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.</description>
          </group>
          <group group_id="O2">
            <title>Sham rTMS/Active Fluoxetine</title>
            <description>Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.&#xD;
Fluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.&#xD;
Sham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.</description>
          </group>
          <group group_id="O3">
            <title>Sham rTMS/Placebo Fluoxetine</title>
            <description>Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of placebo fluoxetine by mouth daily.&#xD;
Sham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.&#xD;
Placebo Fluoxetine: Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Fugl-Meyer Assessment (FMA) Scale</title>
          <description>The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation, and joint functioning in patients with post-stroke hemiplegia. We used the upper limb motor function subscale: minimum values= 0 ; maximum values= 66. Higher scores mean a better outcome. Changes from baseline to 90 days (value at 90 days minus value at baseline).</description>
          <population>Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments</population>
          <units>units on a scale</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="10.10" lower_limit="4.06" upper_limit="16.14"/>
                    <measurement group_id="O2" value="6.73" lower_limit="1.28" upper_limit="12.17"/>
                    <measurement group_id="O3" value="15.55" lower_limit="9.16" upper_limit="21.95"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Changes in Cortical Excitability Measures</title>
        <description>We will measure cortical excitability using single-pulsed transcranial magnetic stimulation (TMS) before and after stimulation at three different time-points. Changes from baseline to 90 days (value at 90 days minus value at baseline).</description>
        <time_frame>Baseline and 90 days</time_frame>
        <population>Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments</population>
        <group_list>
          <group group_id="O1">
            <title>Active rTMS/Active Fluoxetine</title>
            <description>Subjects in this arm will undergo 10 daily sessions over 15 days of active low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of active low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.&#xD;
Active Repetitive Transcranial Magnetic Stimulation (rTMS): Subjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.&#xD;
Fluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.</description>
          </group>
          <group group_id="O2">
            <title>Sham rTMS/Active Fluoxetine</title>
            <description>Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.&#xD;
Fluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.&#xD;
Sham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.</description>
          </group>
          <group group_id="O3">
            <title>Sham rTMS/Placebo Fluoxetine</title>
            <description>Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of placebo fluoxetine by mouth daily.&#xD;
Sham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.&#xD;
Placebo Fluoxetine: Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days.</description>
          </group>
        </group_list>
        <measure>
          <title>Changes in Cortical Excitability Measures</title>
          <description>We will measure cortical excitability using single-pulsed transcranial magnetic stimulation (TMS) before and after stimulation at three different time-points. Changes from baseline to 90 days (value at 90 days minus value at baseline).</description>
          <population>Performed by a rater blinded to rTMS and pharmacotherapy performed all assessments</population>
          <units>motor evoked potential (mV)</units>
          <param>Mean</param>
          <dispersion>95% Confidence Interval</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="9"/>
                <count group_id="O2" value="10"/>
                <count group_id="O3" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-0.05" lower_limit="-0.34" upper_limit="0.08"/>
                    <measurement group_id="O2" value="-0.12" lower_limit="-0.33" upper_limit="0.43"/>
                    <measurement group_id="O3" value="0.33" lower_limit="0.07" upper_limit="1.16"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>3 months</time_frame>
      <desc>adverse effects were collected with a questionnaire for adverse effects</desc>
      <group_list>
        <group group_id="E1">
          <title>Active rTMS/Active Fluoxetine</title>
          <description>Subjects in this arm will undergo 10 daily sessions over 15 days of active low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of active low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.&#xD;
Active Repetitive Transcranial Magnetic Stimulation (rTMS): Subjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.&#xD;
Fluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.</description>
        </group>
        <group group_id="E2">
          <title>Sham rTMS/Active Fluoxetine</title>
          <description>Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.&#xD;
Fluoxetine: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.&#xD;
Sham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.</description>
        </group>
        <group group_id="E3">
          <title>Sham rTMS/Placebo Fluoxetine</title>
          <description>Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of placebo fluoxetine by mouth daily.&#xD;
Sham repetitive transcranial magnetic stimulation (rTMS): Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.&#xD;
Placebo Fluoxetine: Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days.</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="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <default_assessment>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="9"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" subjects_affected="3" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
          <category>
            <title>Nervous system disorders</title>
            <event_list>
              <event>
                <sub_title>Headache</sub_title>
                <counts group_id="E1" events="3" subjects_affected="2" subjects_at_risk="9"/>
                <counts group_id="E2" events="0" subjects_affected="0" subjects_at_risk="10"/>
                <counts group_id="E3" events="6" subjects_affected="3" subjects_at_risk="8"/>
              </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>Dr. Felipe Fregni</name_or_title>
      <organization>Spaulding Rehabilitation Hospital</organization>
      <phone>6179526158</phone>
      <email>fregni.felipe@mgh.harvard.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/NCT02208466
org study id: 2014P001046
nct id: NCT02208466
lead sponsor: 
has dmc: No
In this study investigator's aim to assess the effect of a type of non-invasive brain
      stimulation technique called repetitive transcranial magnetic stimulation (rTMS) in
      conjunction with fluoxetine on motor recovery after stroke.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Investigator, Outcomes Assessor)
measure: Changes in Motor Function (Jebsen-Taylor Task)
time frame: baseline and 90 days
description: Jebsen Taylor Hand Function Test: measures hand function in real-life activities, by evaluating the time required to perform 7 different tasks. We used the non-constrained hand for the assessments. The sum of the different tasks was used for the analysis.
Calculation details: value at 9 months minus value at baseline, change in seconds (adjusted mean difference).
measure: Changes in Fugl-Meyer Assessment (FMA) Scale
time frame: baseline and 90 days
description: The Fugl-Meyer Assessment (FMA) is a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation, and joint functioning in patients with post-stroke hemiplegia. We used the upper limb motor function subscale: minimum values= 0 ; maximum values= 66. Higher scores mean a better outcome. Changes from baseline to 90 days (value at 90 days minus value at baseline).
measure: Changes in Cortical Excitability Measures
time frame: Baseline and 90 days
description: We will measure cortical excitability using single-pulsed transcranial magnetic stimulation (TMS) before and after stimulation at three different time-points. Changes from baseline to 90 days (value at 90 days minus value at baseline).
arm group label: Active rTMS/active fluoxetine
arm group type: Experimental
description: Subjects in this arm will undergo 10 daily sessions over 15 days of active low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of active low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.
arm group label: Sham rTMS/active fluoxetine
arm group type: Experimental
description: Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of active fluoxetine by mouth daily.
arm group label: Sham rTMS/placebo fluoxetine
arm group type: Experimental
description: Subjects in this arm will undergo 10 daily sessions over 15 days of sham low-frequency rTMS with each session lasting 20 minutes. This will be followed by 8 weekly sessions of sham low-frequency rTMS with each session lasting 20 minutes. Additionally, during this time beginning with enrollment, subjects will also be taking 20mg of placebo fluoxetine by mouth daily.
intervention type: Device
intervention name: Active Repetitive Transcranial Magnetic Stimulation (rTMS)
description: Subjects will undergo active low-frequency rTMS (1Hz continuous). Each session will last 20 minutes and will be conducted at 100% of the motor threshold.
arm group label: Active rTMS/active fluoxetine
other name: magnetic stimulation, Magstim
intervention type: Drug
intervention name: Fluoxetine
description: Subjects will receive active fluoxetine (20mg) and take orally consecutively for 90 days.
arm group label: Active rTMS/active fluoxetine
arm group label: Sham rTMS/active fluoxetine
other name: Prozac, Sarafem, Ladose, Fontex
intervention type: Device
intervention name: Sham repetitive transcranial magnetic stimulation (rTMS)
description: Subjects will undergo sham low-frequency rTMS (using sham coil). This session will last 20 minutes, just as the active session would, however, no magnetic pulses will be delivered.
arm group label: Sham rTMS/active fluoxetine
arm group label: Sham rTMS/placebo fluoxetine
other name: Magstim, magnetic stimulation
intervention type: Drug
intervention name: Placebo Fluoxetine
description: Subject will receive placebo fluoxetine (sugar pills) and will take orally consecutively for 90 days.
arm group label: Sham rTMS/placebo fluoxetine
other name: Prozac, Sarafem, Ladose, Fontex
criteria: 
gender: All
minimum age: 18 Years
maximum age: N/A
healthy volunteers: No
last name: Felipe Fregni, MD PhD MPH
role: Principal Investigator
affiliation: Spaulding Rehabilitation Hospital
facility: 
country: United States
responsible party type: Principal Investigator
investigator affiliation: Spaulding Rehabilitation Hospital
investigator full name: Felipe Fregni
investigator title: Principal Investigator
mesh term: Stroke
mesh term: Fluoxetine
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 