<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/NCT03273270</url>
  </required_header>
  <id_info>
    <org_study_id>TMS/FOG</org_study_id>
    <nct_id>NCT03273270</nct_id>
  </id_info>
  <brief_title>Effects of Neuromodulation and Rehabilitation of the Locomotor Network in Freezing of Gait</brief_title>
  <acronym>TMS/FOG</acronym>
  <official_title>Effects of Neuromodulation and Rehabilitation of the Locomotor Network in Freezing of Gait</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Medical University of South Carolina</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Medical University of South Carolina</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>Yes</is_fda_regulated_device>
    <is_us_export>No</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Freezing of gait (FoG) is a common and debilitating condition in Parkinson's Disease (PD)&#xD;
      patients. FoG is described as an episodic inability to walk, which often triggers falls,&#xD;
      hospitalization and is an important predictor of poor quality of life. As locomotor regions&#xD;
      degenerate in PD, gait automaticity is impaired. Patients compensate by increasing volitional&#xD;
      control of gait, however, this adaptation has been found to worsen FoG severity. We&#xD;
      hypothesize that increased cortical control of gait is maladaptive, and therapies to improve&#xD;
      gait automaticity will not be effective unless cortical control of gait is reduced. The&#xD;
      long-term goal of this project is to develop a therapeutic approach for FoG that&#xD;
      simultaneously reduces cortical control and increases automaticity of gait. The objective is&#xD;
      to determine the locomotor network abnormalities responsible for FoG and demonstrate how&#xD;
      neuromodulation and rehabilitation can modulate the network. The rationale of this study is&#xD;
      that increased connectivity between brainstem locomotor regions and cortical structures&#xD;
      represents increased cortical governance of gait, and it can be reversed by the proposed&#xD;
      intervention. We will accomplish this by combining a course of inhibitory rTMS (1Hz) to the&#xD;
      cortex (supplementary motor area) with a rehabilitation protocol designed to increase gait&#xD;
      automaticity (dual task training). We have designed a study that will carefully assess the&#xD;
      locomotor network of freezers with resting state functional, diffusion and interleaved&#xD;
      TMS/BOLD MRI studies, before and after intervention. Behavioral measures including gait&#xD;
      analysis, cognitive and motor assessments will also be conducted at baseline and post&#xD;
      treatment. The study aims to determine the effects of our intervention on the locomotor&#xD;
      network (assessed with imaging), as well as on FoG severity as quantified through multiple&#xD;
      markers obtained through gait analysis. At the conclusion of the study we expect to have&#xD;
      determined the network changes central to the pathophysiology of FoG, the effects of 1Hz rTMS&#xD;
      + rehabilitation on this network, and on FoG severity.&#xD;
&#xD;
      The relevance of this study to public health is to develop a non-invasive effective&#xD;
      therapeutic option for one of the most debilitating and untreatable conditions affecting the&#xD;
      lives of one million Americans suffering from PD; freezing of gait.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Subjects meeting diagnostic criteria for PD and documented freezing of gait will be recruited&#xD;
      from the MUSC Movement Disorder Clinic by clinical staff. Subjects will undergo identical&#xD;
      imaging protocols before and after intervention. Subjects will undergo ten, 20 minute, dual&#xD;
      task training sessions immediately following each rTMS session. Subjects will be randomized&#xD;
      to either active rTMS + rehabilitation or rehabilitation alone at a 2:1 ratio (10 active: 5&#xD;
      control). The primary outcome measure will be dual task interference for turning.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">July 31, 2017</start_date>
  <completion_date type="Actual">March 23, 2020</completion_date>
  <primary_completion_date type="Actual">March 23, 2020</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, Care Provider, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Change in Functional Connectivity to the Supplementary Motor Area.</measure>
    <time_frame>pre and post intervention (within one week of completion)</time_frame>
    <description>Change (pre vs post intervention) in resting-state fMRI connectivity (fisher z-score) of the supplemental motor area (SMA). A negative change score means there was a reduction in SMA connectivity pre to post intervention. A positive change score means there was an increase in SMA connectivity pre to post intervention.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Change in New Freezing of Gait Questionnaire</measure>
    <time_frame>pre and post intervention (within one week of completion)</time_frame>
    <description>The new freezing of gait questionnaire is a measure of freezing severity (total score range: 0-28) wherein higher scores represent worse freezing behavior. The outcome measures represent the change in freezing of gait questionnaire score from pre to post intervention. A larger, positive value represents a greater reduction in freezing severity and a better outcome.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Change in Dual Task Time to Turn Off</measure>
    <time_frame>pre and post intervention (within one week of completion)</time_frame>
    <description>The time to turn around a cone (in seconds) while dual tasking (performing a serial 7s and/or every other letter of the alphabet task) was measured while participants were in the OFF state (off of their Parkinson's medication). The assessment were performed pre to post intervention. A greater reduction in time to turn (pre versus post interverntion) is represented by a larger positive number. A larger reduction in time to turn represents a better outcome.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">20</enrollment>
  <condition>Parkinson Disease With Freezing of Gait</condition>
  <arm_group>
    <arm_group_label>Active TMS</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>1 Hz repetitive transcranial magnetic stimulation</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Sham TMS</arm_group_label>
    <arm_group_type>Placebo Comparator</arm_group_type>
    <description>No active stimulation</description>
  </arm_group>
  <intervention>
    <intervention_type>Radiation</intervention_type>
    <intervention_name>transcranial magnetic stimulation</intervention_name>
    <description>transcranial magnetic stimulation</description>
    <arm_group_label>Active TMS</arm_group_label>
    <arm_group_label>Sham TMS</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Subjects meeting diagnostic criteria for PD and documented FoG&#xD;
&#xD;
        -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Subjects with contraindications to MRI, or TMS (no history of seizures, no metal&#xD;
             implants in head, no pregnancy) dementia, or inability to complete the walk 30 feet in&#xD;
             the off state without assistance will be excluded.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>N/A</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Gonzalo Revuelta, DO</last_name>
    <role>Principal Investigator</role>
    <affiliation>Medical University of South Carolina</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Medical University of South Carolina</name>
      <address>
        <city>Charleston</city>
        <state>South Carolina</state>
        <zip>29425</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>August 28, 2017</study_first_submitted>
  <study_first_submitted_qc>September 2, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 6, 2017</study_first_posted>
  <results_first_submitted>February 10, 2021</results_first_submitted>
  <results_first_submitted_qc>March 3, 2021</results_first_submitted_qc>
  <results_first_posted type="Actual">March 29, 2021</results_first_posted>
  <last_update_submitted>March 3, 2021</last_update_submitted>
  <last_update_submitted_qc>March 3, 2021</last_update_submitted_qc>
  <last_update_posted type="Actual">March 29, 2021</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Parkinson Disease</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>June 17, 2019</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/70/NCT03273270/Prot_SAP_000.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>Active TMS + Gait Training</title>
          <description>1 Hz repetitive transcranial magnetic stimulation&#xD;
transcranial magnetic stimulation: transcranial magnetic stimulation</description>
        </group>
        <group group_id="P2">
          <title>Sham TMS + Gait Training</title>
          <description>No active stimulation&#xD;
transcranial magnetic stimulation: transcranial magnetic stimulation</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" count="8"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="12"/>
                <participants group_id="P2" 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_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Active TMS + Gait Training</title>
          <description>1 Hz repetitive transcranial magnetic stimulation&#xD;
transcranial magnetic stimulation: transcranial magnetic stimulation</description>
        </group>
        <group group_id="B2">
          <title>Sham TMS + Gait Training</title>
          <description>No active stimulation&#xD;
transcranial magnetic stimulation: transcranial magnetic stimulation</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="12"/>
            <count group_id="B2" value="8"/>
            <count group_id="B3" value="20"/>
          </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="66.6" spread="7.5"/>
                    <measurement group_id="B2" value="64.5" spread="8.9"/>
                    <measurement group_id="B3" value="65.8" spread="7.9"/>
                  </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="5"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="7"/>
                    <measurement group_id="B2" value="7"/>
                    <measurement group_id="B3" value="14"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Ethnicity (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>Hispanic or Latino</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>
                  <title>Not Hispanic or Latino</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="15"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Race (NIH/OMB)</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>American Indian or Alaska Native</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Asian</title>
                  <measurement_list>
                    <measurement group_id="B1" value="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="1"/>
                    <measurement group_id="B2" value="1"/>
                    <measurement group_id="B3" value="2"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="9"/>
                    <measurement group_id="B2" value="5"/>
                    <measurement group_id="B3" value="14"/>
                  </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="2"/>
                    <measurement group_id="B2" value="2"/>
                    <measurement group_id="B3" value="4"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <measure>
          <title>Region of Enrollment</title>
          <units>participants</units>
          <param>Number</param>
          <class_list>
            <class>
              <title>United States</title>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="B1" value="12"/>
                    <measurement group_id="B2" value="8"/>
                    <measurement group_id="B3" value="20"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Change in Functional Connectivity to the Supplementary Motor Area.</title>
        <description>Change (pre vs post intervention) in resting-state fMRI connectivity (fisher z-score) of the supplemental motor area (SMA). A negative change score means there was a reduction in SMA connectivity pre to post intervention. A positive change score means there was an increase in SMA connectivity pre to post intervention.</description>
        <time_frame>pre and post intervention (within one week of completion)</time_frame>
        <population>participant did not receive post scan due to discomfort in scanner</population>
        <group_list>
          <group group_id="O1">
            <title>Active TMS + Gait Training</title>
            <description>1 Hz repetitive transcranial magnetic stimulation&#xD;
transcranial magnetic stimulation: transcranial magnetic stimulation</description>
          </group>
          <group group_id="O2">
            <title>Sham TMS + Gait Training</title>
            <description>No active stimulation&#xD;
transcranial magnetic stimulation: transcranial magnetic stimulation</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Functional Connectivity to the Supplementary Motor Area.</title>
          <description>Change (pre vs post intervention) in resting-state fMRI connectivity (fisher z-score) of the supplemental motor area (SMA). A negative change score means there was a reduction in SMA connectivity pre to post intervention. A positive change score means there was an increase in SMA connectivity pre to post intervention.</description>
          <population>participant did not receive post scan due to discomfort in scanner</population>
          <units>z-score</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="11"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="-.176" spread=".102"/>
                    <measurement group_id="O2" value=".190" spread="0.119"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in New Freezing of Gait Questionnaire</title>
        <description>The new freezing of gait questionnaire is a measure of freezing severity (total score range: 0-28) wherein higher scores represent worse freezing behavior. The outcome measures represent the change in freezing of gait questionnaire score from pre to post intervention. A larger, positive value represents a greater reduction in freezing severity and a better outcome.</description>
        <time_frame>pre and post intervention (within one week of completion)</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Active TMS + Gait Training</title>
            <description>1 Hz repetitive transcranial magnetic stimulation&#xD;
transcranial magnetic stimulation: transcranial magnetic stimulation</description>
          </group>
          <group group_id="O2">
            <title>Sham TMS + Gait Training</title>
            <description>No active stimulation&#xD;
transcranial magnetic stimulation: transcranial magnetic stimulation</description>
          </group>
        </group_list>
        <measure>
          <title>Change in New Freezing of Gait Questionnaire</title>
          <description>The new freezing of gait questionnaire is a measure of freezing severity (total score range: 0-28) wherein higher scores represent worse freezing behavior. The outcome measures represent the change in freezing of gait questionnaire score from pre to post intervention. A larger, positive value represents a greater reduction in freezing severity and a better outcome.</description>
          <units>score 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="12"/>
                <count group_id="O2" value="8"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="4.83" spread="5.72"/>
                    <measurement group_id="O2" value="1.75" spread="3.24"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Secondary</type>
        <title>Change in Dual Task Time to Turn Off</title>
        <description>The time to turn around a cone (in seconds) while dual tasking (performing a serial 7s and/or every other letter of the alphabet task) was measured while participants were in the OFF state (off of their Parkinson's medication). The assessment were performed pre to post intervention. A greater reduction in time to turn (pre versus post interverntion) is represented by a larger positive number. A larger reduction in time to turn represents a better outcome.</description>
        <time_frame>pre and post intervention (within one week of completion)</time_frame>
        <population>Missing a pre to post measurement for one participant in the sham group</population>
        <group_list>
          <group group_id="O1">
            <title>Active TMS + Gait Training</title>
            <description>1 Hz repetitive transcranial magnetic stimulation&#xD;
transcranial magnetic stimulation: transcranial magnetic stimulation</description>
          </group>
          <group group_id="O2">
            <title>Sham TMS + Gait Training</title>
            <description>No active stimulation&#xD;
transcranial magnetic stimulation: transcranial magnetic stimulation</description>
          </group>
        </group_list>
        <measure>
          <title>Change in Dual Task Time to Turn Off</title>
          <description>The time to turn around a cone (in seconds) while dual tasking (performing a serial 7s and/or every other letter of the alphabet task) was measured while participants were in the OFF state (off of their Parkinson's medication). The assessment were performed pre to post intervention. A greater reduction in time to turn (pre versus post interverntion) is represented by a larger positive number. A larger reduction in time to turn represents a better outcome.</description>
          <population>Missing a pre to post measurement for one participant in the sham group</population>
          <units>seconds</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="12"/>
                <count group_id="O2" value="7"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="12.05" spread="40.52"/>
                    <measurement group_id="O2" value="5.88" spread="11.94"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>The participants were continuously assessed for the duration of the TMS administration sessions and at pre and post intervention visits. This occurred over the time course of two weeks in which the participant was actively participating in the study.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Active TMS + Gait Training</title>
          <description>1 Hz repetitive transcranial magnetic stimulation&#xD;
transcranial magnetic stimulation: transcranial magnetic stimulation</description>
        </group>
        <group group_id="E2">
          <title>Sham TMS + Gait Training</title>
          <description>No active stimulation&#xD;
transcranial magnetic stimulation: transcranial magnetic stimulation</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="12"/>
                <counts group_id="E2" 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="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>0</frequency_threshold>
        <category_list>
          <category>
            <title>Total</title>
            <event_list>
              <event>
                <sub_title>Total, other adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="12"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="8"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <limitations_and_caveats>Multiple variables were collected with gait analysis (i.e. velocity, step length, time) however, we hypothesized dual task time to turn during the OFF conditions would be most likely to change pre to post intervention. In order to minimize multiple comparisons among gait measures dual task time to turn was selected as the most important variable to detect freezing since turning and dual tasking are common triggers.</limitations_and_caveats>
    <point_of_contact>
      <name_or_title>Gonzalo Revuelta</name_or_title>
      <organization>Medical University of South Carolina</organization>
      <phone>7927262</phone>
      <email>revuelta@musc.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/NCT03273270
org study id: TMS/FOG
nct id: NCT03273270
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: No
Freezing of gait (FoG) is a common and debilitating condition in Parkinson's Disease (PD)
      patients. FoG is described as an episodic inability to walk, which often triggers falls,
      hospitalization and is an important predictor of poor quality of life. As locomotor regions
      degenerate in PD, gait automaticity is impaired. Patients compensate by increasing volitional
      control of gait, however, this adaptation has been found to worsen FoG severity. We
      hypothesize that increased cortical control of gait is maladaptive, and therapies to improve
      gait automaticity will not be effective unless cortical control of gait is reduced. The
      long-term goal of this project is to develop a therapeutic approach for FoG that
      simultaneously reduces cortical control and increases automaticity of gait. The objective is
      to determine the locomotor network abnormalities responsible for FoG and demonstrate how
      neuromodulation and rehabilitation can modulate the network. The rationale of this study is
      that increased connectivity between brainstem locomotor regions and cortical structures
      represents increased cortical governance of gait, and it can be reversed by the proposed
      intervention. We will accomplish this by combining a course of inhibitory rTMS (1Hz) to the
      cortex (supplementary motor area) with a rehabilitation protocol designed to increase gait
      automaticity (dual task training). We have designed a study that will carefully assess the
      locomotor network of freezers with resting state functional, diffusion and interleaved
      TMS/BOLD MRI studies, before and after intervention. Behavioral measures including gait
      analysis, cognitive and motor assessments will also be conducted at baseline and post
      treatment. The study aims to determine the effects of our intervention on the locomotor
      network (assessed with imaging), as well as on FoG severity as quantified through multiple
      markers obtained through gait analysis. At the conclusion of the study we expect to have
      determined the network changes central to the pathophysiology of FoG, the effects of 1Hz rTMS
      + rehabilitation on this network, and on FoG severity.

      The relevance of this study to public health is to develop a non-invasive effective
      therapeutic option for one of the most debilitating and untreatable conditions affecting the
      lives of one million Americans suffering from PD; freezing of gait.
Subjects meeting diagnostic criteria for PD and documented freezing of gait will be recruited
      from the MUSC Movement Disorder Clinic by clinical staff. Subjects will undergo identical
      imaging protocols before and after intervention. Subjects will undergo ten, 20 minute, dual
      task training sessions immediately following each rTMS session. Subjects will be randomized
      to either active rTMS + rehabilitation or rehabilitation alone at a 2:1 ratio (10 active: 5
      control). The primary outcome measure will be dual task interference for turning.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Triple (Participant, Care Provider, Investigator)
measure: Change in Functional Connectivity to the Supplementary Motor Area.
time frame: pre and post intervention (within one week of completion)
description: Change (pre vs post intervention) in resting-state fMRI connectivity (fisher z-score) of the supplemental motor area (SMA). A negative change score means there was a reduction in SMA connectivity pre to post intervention. A positive change score means there was an increase in SMA connectivity pre to post intervention.
measure: Change in New Freezing of Gait Questionnaire
time frame: pre and post intervention (within one week of completion)
description: The new freezing of gait questionnaire is a measure of freezing severity (total score range: 0-28) wherein higher scores represent worse freezing behavior. The outcome measures represent the change in freezing of gait questionnaire score from pre to post intervention. A larger, positive value represents a greater reduction in freezing severity and a better outcome.
measure: Change in Dual Task Time to Turn Off
time frame: pre and post intervention (within one week of completion)
description: The time to turn around a cone (in seconds) while dual tasking (performing a serial 7s and/or every other letter of the alphabet task) was measured while participants were in the OFF state (off of their Parkinson's medication). The assessment were performed pre to post intervention. A greater reduction in time to turn (pre versus post interverntion) is represented by a larger positive number. A larger reduction in time to turn represents a better outcome.
arm group label: Active TMS
arm group type: Experimental
description: 1 Hz repetitive transcranial magnetic stimulation
arm group label: Sham TMS
arm group type: Placebo Comparator
description: No active stimulation
intervention type: Radiation
intervention name: transcranial magnetic stimulation
description: transcranial magnetic stimulation
arm group label: Active TMS
arm group label: Sham TMS
criteria: 
gender: All
minimum age: N/A
maximum age: N/A
healthy volunteers: No
last name: Gonzalo Revuelta, DO
role: Principal Investigator
affiliation: Medical University of South Carolina
facility: 
country: United States
responsible party type: Sponsor
mesh term: Parkinson Disease
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
limitations and caveats: Multiple variables were collected with gait analysis (i.e. velocity, step length, time) however, we hypothesized dual task time to turn during the OFF conditions would be most likely to change pre to post intervention. In order to minimize multiple comparisons among gait measures dual task time to turn was selected as the most important variable to detect freezing since turning and dual tasking are common triggers.
point of contact: 