<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/NCT03757819</url>
  </required_header>
  <id_info>
    <org_study_id>201810705</org_study_id>
    <nct_id>NCT03757819</nct_id>
  </id_info>
  <brief_title>Transcranial Direct Current Stimulation and Walking in Multiple Sclerosis</brief_title>
  <official_title>Can Transcranial Direct Stimulation Improve Walking in Multiple Sclerosis?</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Thorsten Rudroff</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>University of Iowa</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>Yes</is_us_export>
  </oversight_info>
  <brief_summary>
    <textblock>
      Weakness on one side of the body is a hallmark of Multiple Sclerosis (MS), which has been&#xD;
      determined to be a significant cause of progressive worsening of walking abilities.&#xD;
      Currently, there are no efficient rehabilitation strategies available to target strength&#xD;
      asymmetries and walking impairments. Many of the current treatments, including&#xD;
      pharmaceuticals, are only mildly effective and are often very expensive. Thus, the&#xD;
      development of practical, inexpensive, and effective adjunct treatments is needed.&#xD;
&#xD;
      The study is to examine the efficacy of different tDCS protocols at improving walking in&#xD;
      PwMS. Although the details of the studies slightly vary, the global aspects of the&#xD;
      experimental procedures are identical with the exception that the tDCS stimulation parameter&#xD;
      timing differs between the groups. The study will be double-blind, sham-controlled,&#xD;
      randomized cross-over design.&#xD;
&#xD;
      Maximal voluntary contractions (MVCs) of the right and left knee extensors, knee flexors, hip&#xD;
      flexors, and dorsiflexors will be performed to determine the more-affected leg.&#xD;
&#xD;
      The study compromises 2 groups of subjects which will attend the lab for three sessions. In&#xD;
      the first session subjects will be consented, complete the PDDS, the Fatigue Severity Scale&#xD;
      (FSS), and a 6 minute walk test (6-MWT) for baseline performance. The second session will&#xD;
      involve a 6 MWT performed in association with 2 conditions. Group 1: DURINGtDCS, DURINGSHAM.&#xD;
      Group 2: BEFOREtDCS, BEFORESHAM. The conditions in each group will be in a randomized order.&#xD;
      Intensity of tDCS will be 2mA for both groups. Group 1 will receive the conditions during the&#xD;
      6 MWT. tDCS for 6 min has been shown to be sufficient to induce cortical excitability. Group&#xD;
      2 will receive 13 min of tDCS or sham, which results in after effects lasting through the&#xD;
      completion of the 6 MWT. tDCS will be applied to the motor cortex (M1) corresponding to the&#xD;
      more-affected leg either before or during the 6 min walk test&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      Prospective participants, men and women with MS, will be recruited. To accomplish this study,&#xD;
      each of the two groups of participants will need to complete 3 sessions at the INPL, each&#xD;
      separated by 5-8 days. The duration of each session will be approximately one hour. The&#xD;
      investigators expect data collection to last 6 months.&#xD;
&#xD;
      The study compromises 2 groups of subjects which will attend the lab for three sessions. In&#xD;
      the first session subjects will be consented, complete the Patient Determined Disease Steps&#xD;
      (PDDS) questionnaire, the Fatigue Severity Scale (FSS), and a 6MWT for baseline performance.&#xD;
      The second session will involve a 6 MWT performed in association with 2 conditions. Group 1:&#xD;
      DURING_tDCS, DURING_SHAM. Group 2: BEFORE_tDCS, BEFORE_SHAM. tDCS will be applied first&#xD;
      follwed by SHAM in each group. Intensity of tDCS will be 2mA for both groups. Group 1 will&#xD;
      receive the conditions during the 6 MWT. tDCS for 6 min has been shown to be sufficient to&#xD;
      induce cortical excitability. Group 2 will receive 13 min of tDCS or sham which results in&#xD;
      after effects lasting through the completion of the 6MWT. tDCS will be applied to the motor&#xD;
      cortex (M1)corresponding to the more-affected leg either before or during the 6 min walk&#xD;
      test. Leg strength, 6 MWT, and tDCS: Maximal voluntary contractions (MVCs) of the right and&#xD;
      left knee extensors, knee flexors, hip flexors, and dorsiflexors will be performed to&#xD;
      determine the more-affected leg. When leg strength difference is less than 10%, the more&#xD;
      affected side will be based on self-report. For the 6 MWT, participants will be asked to walk&#xD;
      as far as they can in 6 minutes. The 6 MWT is well established in MS research and, in order&#xD;
      to measure fatigability as a secondary outcome, the literature suggest using a 6MWT rather&#xD;
      than a 2MWT.Participants will walk in a cordoned off hallway between two cones placed&#xD;
      approximately 30 meters apart. The primary outcome measure will be the distance covered in&#xD;
      the 6 MWT. Since the investigators hypothesize that tDCS will alter the utilization of their&#xD;
      more-affected leg, standard gait metrics during the 6MWT including gait speed, cadence,&#xD;
      stride length and time, step length and time will be assessed with inertial sensors (OPAL&#xD;
      system) for tDCS and SHAM (secondary outcomes). Furthermore, the investigators will calculate&#xD;
      the distance walked index (DWI, distance Min 1 - distance Min 6), which is an objective&#xD;
      measure of fatigability. A tDCS device (ActivaDose II) will deliver a small direct current&#xD;
      through two sponge surface electrodes (5cm × 5cm,soaked with 15 mM NaCL). The positive&#xD;
      electrode will be placed over the motor cortex representation of the more affected leg, and a&#xD;
      second electrode will be placed on the forehead above the contralateral orbit. The following&#xD;
      sessions will be performed in randomized order. Group 1 (During) - (A) The participant will&#xD;
      receive tDCS or SHAM throughout the walking. In the tDCS trial the intensity will start at 0&#xD;
      mA and will be increased to 2mA over a 30 second period of time. At the 6:30 minute time&#xD;
      point (immediately after walking) the current will gradually be reduced from 2 mA to 0 mA.&#xD;
      (B) In the sham condition the participants will only receive the initial 30 seconds of&#xD;
      stimulation, after which the current will be set to 0. Group 2 (Before) - (C) After a 30s&#xD;
      ramp-up, tDCS will be delivered for 13 minutes at an intensity of 2 mA before the 6 min walk&#xD;
      test. At the 13:00 minute time point the current will gradually be reduced from 2 mA to 0 mA.&#xD;
      (D) Participants who undergo a sham condition will only receive the initial 30 seconds of&#xD;
      ramp-up, after which the current will be set to 0 (D). In session 3, the condition not&#xD;
      performed during session 2 will be performed. E.g., if a patient in Group 1 was randomly&#xD;
      assigned DURING_SHAM for session 2, the patient will perform DURING_tDCS in session 3. All&#xD;
      other testing conditions will be the same as session 2.&#xD;
&#xD;
      There will be no long-term follow up.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date type="Actual">February 25, 2019</start_date>
  <completion_date type="Actual">July 7, 2019</completion_date>
  <primary_completion_date type="Actual">July 7, 2019</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>Sequential Assignment</intervention_model>
    <intervention_model_description>This study employed a double-blind, sham-controlled, parallel-randomized crossover design. Each participant attended three sessions. In the first session, participants were consented and completed the Patient-Determined Disease State and Fatigue Severity Scale questionnaires. Then, after a counter-balanced randomization into BEFORE or DURING groups, the participants completed a 6-Minute Walk Test for baseline/familiarization purposes. The second and third sessions involved brain stimulation or sham stimulation either before or during a 6-Minute Walk Test, depending on group assignment. The brain stimulation was randomly assigned to either session two or three, and sham stimulation was performed in the other session.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Investigator)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Distance Walked on a Treadmill With tDCS</measure>
    <time_frame>one week</time_frame>
    <description>6 min walk test</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Distance Walked on a Treadmill With SHAM</measure>
    <time_frame>one week</time_frame>
    <description>6 min walk test</description>
  </primary_outcome>
  <other_outcome>
    <measure>Leg Strength Data</measure>
    <time_frame>one week</time_frame>
    <description>Leg extensor strength and Leg flexor strength data were obtained but have not been used for data analysis.</description>
  </other_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Actual">12</enrollment>
  <condition>Transcranial Direct Current Stimulation</condition>
  <arm_group>
    <arm_group_label>Before Walking tDCS first then SHAM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To investigate the effects of tDCS applied before walking versus during to evaluate effectiveness of the intervention.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>During Walking tDCS first then SHAM</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To investigate the effects of tDCS applied before walking versus during to evaluate effectiveness of the intervention.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>tDCS</intervention_name>
    <description>Brain Stimulation</description>
    <arm_group_label>Before Walking tDCS first then SHAM</arm_group_label>
    <arm_group_label>During Walking tDCS first then SHAM</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>SHAM</intervention_name>
    <description>Placebo device</description>
    <arm_group_label>Before Walking tDCS first then SHAM</arm_group_label>
    <arm_group_label>During Walking tDCS first then SHAM</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  medically diagnosed with Multiple Sclerosis,&#xD;
&#xD;
          -  moderate disability (Patient Determined Disease Steps (PDDS) core 2-6), -self--&#xD;
             reported differences in function between legs, able to walk for 6min. -&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  relapse within last 60 days,&#xD;
&#xD;
          -  high risk for cardiovascular disease (ACSM risk classification),&#xD;
&#xD;
          -  changes in disease modifying medications within last 45 days,&#xD;
&#xD;
          -  concurrent neurological/neuromuscular disease,&#xD;
&#xD;
          -  hospitalization within last 90 days,&#xD;
&#xD;
          -  diagnosed depression, inability to understand/sign informed consent.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>18 Years</minimum_age>
    <maximum_age>70 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Thorsten Rudroff</last_name>
    <role>Principal Investigator</role>
    <affiliation>University of Iowa</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>University of Iowa</name>
      <address>
        <city>Iowa City</city>
        <state>Iowa</state>
        <zip>52242</zip>
        <country>United States</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <verification_date>November 2022</verification_date>
  <study_first_submitted>November 27, 2018</study_first_submitted>
  <study_first_submitted_qc>November 27, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">November 29, 2018</study_first_posted>
  <results_first_submitted>August 9, 2021</results_first_submitted>
  <results_first_submitted_qc>November 26, 2022</results_first_submitted_qc>
  <results_first_posted type="Actual">December 21, 2022</results_first_posted>
  <last_update_submitted>November 26, 2022</last_update_submitted>
  <last_update_submitted_qc>November 26, 2022</last_update_submitted_qc>
  <last_update_posted type="Actual">December 21, 2022</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor-Investigator</responsible_party_type>
    <investigator_affiliation>University of Iowa</investigator_affiliation>
    <investigator_full_name>Thorsten Rudroff</investigator_full_name>
    <investigator_title>Principal Investigator</investigator_title>
  </responsible_party>
  <keyword>Multiple Scerosis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Multiple Sclerosis</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Study Protocol, Statistical Analysis Plan, and Informed Consent Form</document_type>
      <document_has_protocol>Yes</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>Yes</document_has_sap>
      <document_date>June 20, 2022</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/19/NCT03757819/Prot_SAP_ICF_004.pdf</document_url>
    </provided_document>
  </provided_document_section>

  <clinical_results>

    <participant_flow>
      <group_list>
        <group group_id="P1">
          <title>BEFORE Walking, SHAM First Then tDCS</title>
          <description>In the BEFORE walking group, received SHAM in session two and tDCS in session three.</description>
        </group>
        <group group_id="P2">
          <title>BEFORE Walking, tDCS First Then SHAM</title>
          <description>In the BEFORE walking group, received tDCS in session two and then SHAM in session three.</description>
        </group>
        <group group_id="P3">
          <title>DURING Walking, SHAM First Then tDCS</title>
          <description>In the DURING walking group, received SHAM in session two and then tDCS in session three.</description>
        </group>
        <group group_id="P4">
          <title>DURING Walking, tDCS First Then SHAM</title>
          <description>In the DURING walking group, received tDCS in session two and then SHAM in session three.</description>
        </group>
      </group_list>
      <period_list>
        <period>
          <title>Overall Study</title>
          <milestone_list>
            <milestone>
              <title>STARTED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="3"/>
              </participants_list>
            </milestone>
            <milestone>
              <title>COMPLETED</title>
              <participants_list>
                <participants group_id="P1" count="3"/>
                <participants group_id="P2" count="3"/>
                <participants group_id="P3" count="3"/>
                <participants group_id="P4" count="3"/>
              </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 group_id="P4" count="0"/>
              </participants_list>
            </milestone>
          </milestone_list>
        </period>
      </period_list>
    </participant_flow>

    <baseline>
      <group_list>
        <group group_id="B1">
          <title>Before Walking tDCS/SHAM</title>
          <description>To investigate the effects of tDCS applied before walking versus during to evaluate effectiveness of the intervention.&#xD;
tDCS: Brain Stimulation&#xD;
To investigate the effects of SHAM applied before walking versus during to evaluate effectiveness of the intervention.&#xD;
SHAM: Placebo device</description>
        </group>
        <group group_id="B2">
          <title>During Walking tDCS/SHAM</title>
          <description>To investigate the effects of tDCS applied before walking versus during to evaluate effectiveness of the intervention.&#xD;
tDCS: Brain Stimulation&#xD;
To investigate the effects of SHAM applied before walking versus during to evaluate effectiveness of the intervention.&#xD;
SHAM: Placebo device</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="6"/>
            <count group_id="B2" value="6"/>
            <count group_id="B3" value="12"/>
          </count_list>
        </analyzed>
      </analyzed_list>
      <measure_list>
        <measure>
          <title>Age</title>
          <units>Participants</units>
          <param>Count of Participants</param>
          <class_list>
            <class>
              <category_list>
                <category>
                  <title>&lt;=18 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Between 18 and 65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>&gt;=65 years</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
        <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="47" spread="14"/>
                    <measurement group_id="B2" value="56" spread="7"/>
                    <measurement group_id="B3" value="51" spread="11"/>
                  </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="2"/>
                    <measurement group_id="B3" value="6"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Male</title>
                  <measurement_list>
                    <measurement group_id="B1" value="2"/>
                    <measurement group_id="B2" value="4"/>
                    <measurement group_id="B3" value="6"/>
                  </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="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>White</title>
                  <measurement_list>
                    <measurement group_id="B1" value="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
                <category>
                  <title>More than one race</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </measurement_list>
                </category>
                <category>
                  <title>Unknown or Not Reported</title>
                  <measurement_list>
                    <measurement group_id="B1" value="0"/>
                    <measurement group_id="B2" value="0"/>
                    <measurement group_id="B3" value="0"/>
                  </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="6"/>
                    <measurement group_id="B2" value="6"/>
                    <measurement group_id="B3" value="12"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </measure_list>
    </baseline>

    <outcome_list>
      <outcome>
        <type>Primary</type>
        <title>Distance Walked on a Treadmill With tDCS</title>
        <description>6 min walk test</description>
        <time_frame>one week</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Before Walking</title>
            <description>To investigate the effects of tDCS applied before walking to evaluate effectiveness of the intervention.&#xD;
tDCS: Brain Stimulation&#xD;
SHAM: Placebo device</description>
          </group>
          <group group_id="O2">
            <title>During Walking</title>
            <description>To investigate the effects of tDCS applied during to evaluate effectiveness of the intervention.&#xD;
tDCS: Brain Stimulation&#xD;
SHAM: Placebo device</description>
          </group>
        </group_list>
        <measure>
          <title>Distance Walked on a Treadmill With tDCS</title>
          <description>6 min walk test</description>
          <units>m</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="375" spread="78"/>
                    <measurement group_id="O2" value="285" spread="131"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Primary</type>
        <title>Distance Walked on a Treadmill With SHAM</title>
        <description>6 min walk test</description>
        <time_frame>one week</time_frame>
        <group_list>
          <group group_id="O1">
            <title>Before Walking</title>
            <description>To investigate the effects of SHAM applied before walking to evaluate effectiveness of the intervention.&#xD;
tDCS: Brain Stimulation&#xD;
SHAM: Placebo device</description>
          </group>
          <group group_id="O2">
            <title>During Walking</title>
            <description>To investigate the effects of SHAM applied during walking to evaluate effectiveness of the intervention.&#xD;
tDCS: Brain Stimulation&#xD;
SHAM: Placebo device</description>
          </group>
        </group_list>
        <measure>
          <title>Distance Walked on a Treadmill With SHAM</title>
          <description>6 min walk test</description>
          <units>m</units>
          <param>Mean</param>
          <dispersion>Standard Deviation</dispersion>
          <analyzed_list>
            <analyzed>
              <units>Participants</units>
              <scope>Measure</scope>
              <count_list>
                <count group_id="O1" value="6"/>
                <count group_id="O2" value="6"/>
              </count_list>
            </analyzed>
          </analyzed_list>
          <class_list>
            <class>
              <category_list>
                <category>
                  <measurement_list>
                    <measurement group_id="O1" value="366" spread="90"/>
                    <measurement group_id="O2" value="298" spread="133"/>
                  </measurement_list>
                </category>
              </category_list>
            </class>
          </class_list>
        </measure>
      </outcome>
      <outcome>
        <type>Other Pre-specified</type>
        <title>Leg Strength Data</title>
        <description>Leg extensor strength and Leg flexor strength data were obtained but have not been used for data analysis.</description>
        <time_frame>one week</time_frame>
      </outcome>
    </outcome_list>

    <reported_events>
      <time_frame>Through study completion, an average of 2 weeks.</time_frame>
      <group_list>
        <group group_id="E1">
          <title>Before Walking Active/SHAM</title>
          <description>To investigate the effects of tDCS applied before walking to evaluate effectiveness of the intervention.&#xD;
tDCS: Brain Stimulation&#xD;
SHAM: Placebo device</description>
        </group>
        <group group_id="E2">
          <title>During Walking Active/SHAM</title>
          <description>To investigate the effects of tDCS applied during walking to evaluate effectiveness of the intervention.&#xD;
tDCS: Brain Stimulation&#xD;
SHAM: Placebo device</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="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
              <event>
                <sub_title>Total, serious adverse events</sub_title>
                <counts group_id="E1" subjects_affected="0" subjects_at_risk="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </serious_events>
      <other_events>
        <frequency_threshold>5</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="6"/>
                <counts group_id="E2" subjects_affected="0" subjects_at_risk="6"/>
              </event>
            </event_list>
          </category>
        </category_list>
      </other_events>
    </reported_events>

    <certain_agreements>
      <pi_employee>All Principal Investigators ARE employed by the organization sponsoring the study.</pi_employee>
      <restrictive_agreement>There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed. </restrictive_agreement>
    </certain_agreements>
    <point_of_contact>
      <name_or_title>Thorsten Rudroff</name_or_title>
      <organization>University of Iowa</organization>
      <phone>17205323701</phone>
      <email>thorsten-rudroff@uiowa.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/NCT03757819
org study id: 201810705
nct id: NCT03757819
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: Yes
is us export: Yes
Weakness on one side of the body is a hallmark of Multiple Sclerosis (MS), which has been
      determined to be a significant cause of progressive worsening of walking abilities.
      Currently, there are no efficient rehabilitation strategies available to target strength
      asymmetries and walking impairments. Many of the current treatments, including
      pharmaceuticals, are only mildly effective and are often very expensive. Thus, the
      development of practical, inexpensive, and effective adjunct treatments is needed.

      The study is to examine the efficacy of different tDCS protocols at improving walking in
      PwMS. Although the details of the studies slightly vary, the global aspects of the
      experimental procedures are identical with the exception that the tDCS stimulation parameter
      timing differs between the groups. The study will be double-blind, sham-controlled,
      randomized cross-over design.

      Maximal voluntary contractions (MVCs) of the right and left knee extensors, knee flexors, hip
      flexors, and dorsiflexors will be performed to determine the more-affected leg.

      The study compromises 2 groups of subjects which will attend the lab for three sessions. In
      the first session subjects will be consented, complete the PDDS, the Fatigue Severity Scale
      (FSS), and a 6 minute walk test (6-MWT) for baseline performance. The second session will
      involve a 6 MWT performed in association with 2 conditions. Group 1: DURINGtDCS, DURINGSHAM.
      Group 2: BEFOREtDCS, BEFORESHAM. The conditions in each group will be in a randomized order.
      Intensity of tDCS will be 2mA for both groups. Group 1 will receive the conditions during the
      6 MWT. tDCS for 6 min has been shown to be sufficient to induce cortical excitability. Group
      2 will receive 13 min of tDCS or sham, which results in after effects lasting through the
      completion of the 6 MWT. tDCS will be applied to the motor cortex (M1) corresponding to the
      more-affected leg either before or during the 6 min walk test
Prospective participants, men and women with MS, will be recruited. To accomplish this study,
      each of the two groups of participants will need to complete 3 sessions at the INPL, each
      separated by 5-8 days. The duration of each session will be approximately one hour. The
      investigators expect data collection to last 6 months.

      The study compromises 2 groups of subjects which will attend the lab for three sessions. In
      the first session subjects will be consented, complete the Patient Determined Disease Steps
      (PDDS) questionnaire, the Fatigue Severity Scale (FSS), and a 6MWT for baseline performance.
      The second session will involve a 6 MWT performed in association with 2 conditions. Group 1:
      DURING_tDCS, DURING_SHAM. Group 2: BEFORE_tDCS, BEFORE_SHAM. tDCS will be applied first
      follwed by SHAM in each group. Intensity of tDCS will be 2mA for both groups. Group 1 will
      receive the conditions during the 6 MWT. tDCS for 6 min has been shown to be sufficient to
      induce cortical excitability. Group 2 will receive 13 min of tDCS or sham which results in
      after effects lasting through the completion of the 6MWT. tDCS will be applied to the motor
      cortex (M1)corresponding to the more-affected leg either before or during the 6 min walk
      test. Leg strength, 6 MWT, and tDCS: Maximal voluntary contractions (MVCs) of the right and
      left knee extensors, knee flexors, hip flexors, and dorsiflexors will be performed to
      determine the more-affected leg. When leg strength difference is less than 10%, the more
      affected side will be based on self-report. For the 6 MWT, participants will be asked to walk
      as far as they can in 6 minutes. The 6 MWT is well established in MS research and, in order
      to measure fatigability as a secondary outcome, the literature suggest using a 6MWT rather
      than a 2MWT.Participants will walk in a cordoned off hallway between two cones placed
      approximately 30 meters apart. The primary outcome measure will be the distance covered in
      the 6 MWT. Since the investigators hypothesize that tDCS will alter the utilization of their
      more-affected leg, standard gait metrics during the 6MWT including gait speed, cadence,
      stride length and time, step length and time will be assessed with inertial sensors (OPAL
      system) for tDCS and SHAM (secondary outcomes). Furthermore, the investigators will calculate
      the distance walked index (DWI, distance Min 1 - distance Min 6), which is an objective
      measure of fatigability. A tDCS device (ActivaDose II) will deliver a small direct current
      through two sponge surface electrodes (5cm × 5cm,soaked with 15 mM NaCL). The positive
      electrode will be placed over the motor cortex representation of the more affected leg, and a
      second electrode will be placed on the forehead above the contralateral orbit. The following
      sessions will be performed in randomized order. Group 1 (During) - (A) The participant will
      receive tDCS or SHAM throughout the walking. In the tDCS trial the intensity will start at 0
      mA and will be increased to 2mA over a 30 second period of time. At the 6:30 minute time
      point (immediately after walking) the current will gradually be reduced from 2 mA to 0 mA.
      (B) In the sham condition the participants will only receive the initial 30 seconds of
      stimulation, after which the current will be set to 0. Group 2 (Before) - (C) After a 30s
      ramp-up, tDCS will be delivered for 13 minutes at an intensity of 2 mA before the 6 min walk
      test. At the 13:00 minute time point the current will gradually be reduced from 2 mA to 0 mA.
      (D) Participants who undergo a sham condition will only receive the initial 30 seconds of
      ramp-up, after which the current will be set to 0 (D). In session 3, the condition not
      performed during session 2 will be performed. E.g., if a patient in Group 1 was randomly
      assigned DURING_SHAM for session 2, the patient will perform DURING_tDCS in session 3. All
      other testing conditions will be the same as session 2.

      There will be no long-term follow up.
allocation: Randomized
intervention model: Sequential Assignment
intervention model description: This study employed a double-blind, sham-controlled, parallel-randomized crossover design. Each participant attended three sessions. In the first session, participants were consented and completed the Patient-Determined Disease State and Fatigue Severity Scale questionnaires. Then, after a counter-balanced randomization into BEFORE or DURING groups, the participants completed a 6-Minute Walk Test for baseline/familiarization purposes. The second and third sessions involved brain stimulation or sham stimulation either before or during a 6-Minute Walk Test, depending on group assignment. The brain stimulation was randomly assigned to either session two or three, and sham stimulation was performed in the other session.
primary purpose: Treatment
masking: Double (Participant, Investigator)
measure: Distance Walked on a Treadmill With tDCS
time frame: one week
description: 6 min walk test
measure: Distance Walked on a Treadmill With SHAM
time frame: one week
description: 6 min walk test
measure: Leg Strength Data
time frame: one week
description: Leg extensor strength and Leg flexor strength data were obtained but have not been used for data analysis.
arm group label: Before Walking tDCS first then SHAM
arm group type: Experimental
description: To investigate the effects of tDCS applied before walking versus during to evaluate effectiveness of the intervention.
arm group label: During Walking tDCS first then SHAM
arm group type: Experimental
description: To investigate the effects of tDCS applied before walking versus during to evaluate effectiveness of the intervention.
intervention type: Device
intervention name: tDCS
description: Brain Stimulation
arm group label: Before Walking tDCS first then SHAM
arm group label: During Walking tDCS first then SHAM
intervention type: Device
intervention name: SHAM
description: Placebo device
arm group label: Before Walking tDCS first then SHAM
arm group label: During Walking tDCS first then SHAM
criteria: 
gender: All
minimum age: 18 Years
maximum age: 70 Years
healthy volunteers: No
last name: Thorsten Rudroff
role: Principal Investigator
affiliation: University of Iowa
facility: 
country: United States
responsible party type: Sponsor-Investigator
investigator affiliation: University of Iowa
investigator full name: Thorsten Rudroff
investigator title: Principal Investigator
mesh term: Multiple Sclerosis
sharing ipd: No
provided document: 
participant flow: 
baseline: 
outcome list: 
reported events: 
certain agreements: 
point of contact: 