<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/NCT04437251</url>
  </required_header>
  <id_info>
    <org_study_id>IRB#17592- Phase I &amp; II</org_study_id>
    <nct_id>NCT04437251</nct_id>
  </id_info>
  <brief_title>Effect of Brain Stimulation on Stepping Performance in Stroke Survivors and Healthy Adults</brief_title>
  <acronym>Gait</acronym>
  <official_title>Effect of Brain Stimulation on Motor Skill Acquisition in Stroke Survivors and Healthy Adults</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Texas Woman's University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Texas Woman's University</source>
  <oversight_info>
    <has_dmc>No</has_dmc>
    <is_fda_regulated_drug>No</is_fda_regulated_drug>
    <is_fda_regulated_device>No</is_fda_regulated_device>
  </oversight_info>
  <brief_summary>
    <textblock>
      Participants are being asked to participate in a research study conducted by Shih-Chiao&#xD;
      Tseng, PT, Ph.D. at Texas Woman's University. This research study is to determine whether&#xD;
      low-intensive brain stimulation can enhance learning of a leg movement task. The&#xD;
      investigators also want to know if brain stimulation can improve the nerve function and&#xD;
      walking performance. Our goal is to understand any relationship between brain stimulation and&#xD;
      overall movement control improvement. Participants have been invited to join this research if&#xD;
      they have had a stroke before or they are healthy adults aged 21 years or older. Research&#xD;
      evidence shows stroke can induce permanent brain damage and therefore may cause a person to&#xD;
      have trouble learning a new task. This in turn may significantly impact the recovery of motor&#xD;
      function in stroke survivors. In addition, the investigators also want to know how a healthy&#xD;
      person learns this new leg task and see if her/his learning pattern differs from a stroke&#xD;
      survivor.&#xD;
&#xD;
      This study comprises two phases: Phase I study investigates short-term effects of brain&#xD;
      stimulation on leg skill learning and only requires two visits to TWU. The total time&#xD;
      commitment for Phase I study will be about 6.5 hours, 3.5 hours on the first visit and three&#xD;
      hours on the second visit; Phase II study is an expanded version of Phase I study to&#xD;
      investigate long-term effects of brain stimulation on leg skill learning and requires to&#xD;
      complete 12 visits of exercise training paired with brain stimulation over a four-week period&#xD;
      and additional one visit for follow-up test. The total time commitment for Phase II study&#xD;
      will be about 20 hours, a total of 18 hours for 12 exercise training sessions and two hours&#xD;
      for a follow-up test. The investigators hypothesize that people with chronic stroke will show&#xD;
      a slower rate of acquiring this leg skill as compared to healthy adults. The investigators&#xD;
      also hypothesize that co-applying brain stimulation with 12 sessions of exercise training&#xD;
      will enhance skill learning of this leg task for people with chronic stroke and this&#xD;
      12-session exercise program may exert beneficial influences on the nerve function and leg&#xD;
      muscle activation, and consequentially improve motor control for walking.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This study will take place at Texas Woman's University (TWU)-Houston campus and include two&#xD;
      phases: Phase I involves a single-intervention study and Phase II involves a four-week&#xD;
      intervention study. After enrolling to the study, participants can choose to only participate&#xD;
      in the Phase I study or choose to participate in both Phase I and Phase II studies.&#xD;
&#xD;
      Phase I Study - participants will be asked to complete two visits, 1-14 days apart. It will&#xD;
      take about a total of 6.5 hours of their time to complete all tests (3.5 hours for the first&#xD;
      visit and 3 hours for the second visit, two visits). Participants will need to wear&#xD;
      short-sleeve t-shirt, shorts, and a pair of sneakers for testing. During the first visit, the&#xD;
      investigators will measure how well the nervous system works and how well the individual&#xD;
      walks (see details as follows). If participants have had a stroke before, on the first visit&#xD;
      the investigators will do some tests on to make sure participants have good feeling, balance,&#xD;
      and motor responses in their legs. If all tests are good, participants will fill out a form&#xD;
      asking about their medical history. If participants have not had a stroke, the investigators&#xD;
      will ask a few questions to make sure participants do not have any medical issues.&#xD;
&#xD;
      Next, the investigators will ask participants to learn a leg movement task at each visit. The&#xD;
      task is to control and move a computer cursor from a start location to one of three targets&#xD;
      displayed on the computer monitor. Participants will need to make forward, rightward or&#xD;
      leftward foot movements to guide the cursor to one of the targets. The task itself is similar&#xD;
      to the daily computer task performed by a hand mouse. In each visit, it will take&#xD;
      approximately a total of 45 minutes to complete a set of leg reaching task. Several&#xD;
      one-minute rest breaks will be provided as needed during test. Participants will then be&#xD;
      asked to come back for the second visit within 1-14 days later to repeat the same task.&#xD;
      Throughout practice, participants will learn how to control the cursor using their feet. So&#xD;
      the investigators can compare the learning capacity over two visits to best indicate the&#xD;
      change in the learning capacity over time.&#xD;
&#xD;
      The investigators also want to know if participants can learn this motor skill faster with&#xD;
      cutaneous brain stimulation. Participants will receive weak electrical brain stimulation for&#xD;
      20 minutes during leg skill learning. The brain stimulation device that the investigators&#xD;
      used is similar to the commercial product seen in the TV/magazine, called &quot;transcutaneous&#xD;
      electrical Nerve stimulation&quot; in which electrical current is delivered by electrodes for pain&#xD;
      relief and muscle stimulation. In this study, two electrodes, one placed on the top of the&#xD;
      scalp and one placed on the forehead, will deliver weak electrical current for 20 minutes.&#xD;
      Because the investigators set the current intensity at a very low level, it will not cause&#xD;
      any muscle twitches and participants may only feel little tingling sensation in the first 10&#xD;
      seconds. Most of the time, participants likely become accustomed to the stimulation and no&#xD;
      longer feel the stimulation throughout the rest of the session.&#xD;
&#xD;
      Phase II Study - This study is an expanded version of Phase I study. Participants will be&#xD;
      asked to complete 12 visits of exercise training paired with brain stimulation over a&#xD;
      four-week period. It will take about a total of 18 hours of the time to complete all training&#xD;
      sessions (1.5 hour for each visit/training for a total of 12 visits). Participants will need&#xD;
      to wear short-sleeve t-shirt, shorts, and a pair of sneakers for training. Before and after&#xD;
      four-week training, the investigators will measure how well the nervous system works and how&#xD;
      well the participant walks (see details as follows). One week after completion of four-week&#xD;
      training, participants will be asked to come back to repeat the same tests. The investigators&#xD;
      will compare changes in the learning capacity and motor function before and after four-week&#xD;
      training, and at one week after completion of training to best indicate permanent changes in&#xD;
      the learning capacity and motor function over time.&#xD;
&#xD;
      During each visit, the investigators will ask participants to continue learning a leg&#xD;
      movement task same as the Phase I study. The investigators will also ask participants to&#xD;
      learn a similar leg task, call stepping task during standing. This stepping task is very&#xD;
      similar to the leg task in the Phase I study, but is a more advanced task that requires a&#xD;
      good standing balance. The task is to control a computerized marker attached to the foot and&#xD;
      move a computer cursor from a start location to one of three targets displayed on the&#xD;
      computer monitor. Participants will need to make forward, rightward or leftward stepping&#xD;
      movements to guide the cursor to one of the targets. The task itself is similar to stepping&#xD;
      motion during walking. In each visit, it will take approximately a total of 1.5 hour to&#xD;
      complete two sets of leg task training during sitting and standing. Same brain stimulation&#xD;
      used in the Phase I study (see above) will be delivered during the middle of the exercise&#xD;
      training. Several one-minute rest breaks will be provided as needed during training.&#xD;
      Participants will then be asked to come to the laboratory three times per week for four weeks&#xD;
      in order to complete 12 training sessions.&#xD;
&#xD;
      Outcome measures - For the measurement of brain activity, the investigators will put a&#xD;
      recording electrode on the calf muscle in one leg. Five low-intensity brain stimulation will&#xD;
      be delivered to the scalp to trigger the motor responses. Most of the time, participants will&#xD;
      feel single muscle twitch due to the stimulation. It would take a total of 10 minutes to&#xD;
      finish data collection. For the measurement of nerve activity, the investigators will put a&#xD;
      recording electrode on the calf muscle in one leg. Low-intensity electrical stimulation will&#xD;
      be delivered to a nerve behind the knee to trigger motor responses. A series of small tendon&#xD;
      vibration stimuli will be delivered during electrical stimulation to determine the&#xD;
      sensitivity of the nerve. Most of the time, participants will feel nothing or just light&#xD;
      tingling sensation in the stimulated area. It would take a total of 40 minutes to finish data&#xD;
      collection. Several one-minute rest breaks will be provided as needed during test. For the&#xD;
      measurement of walking, the investigators will put sticky markers on both legs and ask&#xD;
      participants to walk normally across a 10-meter walkway for five trials. It would take&#xD;
      approximately a total of 30 minutes to finish data collection. Several one-minute rest breaks&#xD;
      will be provided as needed during test. For the stepping reaction time test, subjects will&#xD;
      stand on the force plates and will be instructed to step forward onto a target marked on the&#xD;
      floor as soon as they sense electrical stimulation delivered to the posterior of the leg. It&#xD;
      would take approximately a total of 40 minutes to finish data collection. Several one-minute&#xD;
      rest breaks will be provided as needed during test.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Recruiting</overall_status>
  <start_date type="Actual">September 26, 2014</start_date>
  <completion_date type="Anticipated">December 31, 2024</completion_date>
  <primary_completion_date type="Anticipated">December 31, 2024</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>
    <intervention_model_description>This study is a double-blinded, randomized controlled study in which participants will be randomly assigned into one of two brain stimulation groups (sham or real brain stimulation) while being evaluated for their ability of learning a leg task in a single session (phase I), and receiving a 12-session leg exercise training program.</intervention_model_description>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Participant, Outcomes Assessor)</masking>
    <masking_description>The participants will not be informed about their group assignments while learning a leg task. The testers who are conducting neurological and walking assessments before and after training will also be blinded from the group assignments.</masking_description>
  </study_design_info>
  <primary_outcome>
    <measure>Changes in stepping reaction time (Phase I)</measure>
    <time_frame>Measure changes in the reaction time before, immediately after (i.e. within a minute), and 30 minutes after a single session of brain stimulation.</time_frame>
    <description>Calculate the time duration for the central nervous system to process information and produce a stepping action.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in stepping reaction time (Phase II)</measure>
    <time_frame>Measure changes in reaction time before training, up to 24 hours after the completion of a 12-session training program, and one week after the completion of a 12-session training program.</time_frame>
    <description>Calculate the time duration for the central nervous system to process information and produce a stepping action.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in walking performance (Phase I)</measure>
    <time_frame>Measure changes in the walking speed before, immediately after (i.e. within a minute), and 30 minutes after a single session of brain stimulation.</time_frame>
    <description>Measure walking speed (meters/second) during ground walking at a self-selected speed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in walking performance (Phase I)</measure>
    <time_frame>Measure changes in the step length symmetry before, immediately after (i.e. within a minute), and 30 minutes after a single session of brain stimulation.</time_frame>
    <description>Measure step length (centimeters) symmetry (left/right) during ground walking at a self-selected speed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in walking performance (Phase II)</measure>
    <time_frame>Measure changes in the walking speed before training, up to 24 hours after the completion of a 12-session training program, and one week after the completion of a 12-session training program.</time_frame>
    <description>Measure walking speed (meters/second) during ground walking at a self-selected speed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in walking performance (Phase II)</measure>
    <time_frame>Measure changes in the step length symmetry before training, up to 24 hours after the completion of a 12-session training program, and one week after the completion of a 12-session training program.</time_frame>
    <description>Measure step length symmetry (left/right) during ground walking at a self-selected speed.</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in nerve function (Phase I)</measure>
    <time_frame>Measure changes in the nerve function before, immediately after (i.e. within a minute), and 30 minutes after a single session of brain stimulation.</time_frame>
    <description>Place a surface electrode on the calf muscle to record muscle activation triggered by electrical stimulation delivered to the motor neurons in the lesioned motor cortex and tibial nerve on the paretic leg to qualify changes in neuronal activity in the primary cortex and in the spinal cord before and after brain stimulation (tDCS).</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Changes in nerve function (Phase II)</measure>
    <time_frame>Measure changes in the nerve function before training, up to 24 hours after the completion of a 12-session training program), and one week after the completion of a 12-session training program.</time_frame>
    <description>Place a surface electrode on the calf muscle to record muscle activation triggered by electrical stimulation delivered to the motor neurons in the lesioned motor cortex and tibial nerve on the paretic leg to qualify changes in neuronal activity in the primary cortex and in the spinal cord before and after brain stimulation (tDCS).</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Mini-mental State Examination (Phase I)</measure>
    <time_frame>Administer Mini-mental State Examination at the first visit before testing and training</time_frame>
    <description>A standardized questionnaires to evaluate the cognitive function consisting of 11 items with a possible summed score ranging from zero to 30. The most widely accepted and frequently used cutoff score for the MMSE is 23, with scores of 23 or lower indicating the presence of cognitive impairment. A higher score means a better cognitive function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Mini-mental State Examination (Phase II)</measure>
    <time_frame>Administer Mini-mental State Examination at the first visit before testing and training</time_frame>
    <description>A standardized questionnaires to evaluate the cognitive function consisting of 11 items with a possible summed score ranging from zero to 30. The most widely accepted and frequently used cutoff score for the MMSE is 23, with scores of 23 or lower indicating the presence of cognitive impairment.A higher score means a better cognitive function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fugl-Meyer Lower Extremity Function Assessment (Phase I)</measure>
    <time_frame>Administer Fugl-Meyer Lower Extremity Function Assessment at the first visit before testing and training</time_frame>
    <description>A standardized questionnaires to evaluate the lower extremity motor function consisting of movement, coordination, and reflex assessments at hip, knee, and ankle. Possible summed scores range from zero to 34. Higher scores indicate higher and better motor function.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Fugl-Meyer Lower Extremity Function Assessment (Phase II)</measure>
    <time_frame>Administer Fugl-Meyer Lower Extremity Function Assessment at the first visit before testing and training</time_frame>
    <description>A standardized questionnaires to evaluate the lower extremity motor function consisting of movement, coordination, and reflex assessments at hip, knee, and ankle. Possible summed scores range from zero to 34. Higher scores indicate higher and better motor function.</description>
  </secondary_outcome>
  <number_of_arms>3</number_of_arms>
  <enrollment type="Anticipated">180</enrollment>
  <condition>Vascular Accident, Brain</condition>
  <condition>CVA (Cerebrovascular Accident)</condition>
  <condition>Gait, Hemiplegic</condition>
  <condition>Spastic Lower Extremity Weakness</condition>
  <arm_group>
    <arm_group_label>Brain stimulation-induced improvements in leg skill learning</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To examine the degree of stimulation-induced improvements in learning capacity between three groups: stroke group, healthy young group, and healthy older group. Up to date, most studies have investigated the effects of brain stimulation on hand skill improvements in healthy young adults; little is known about stimulation-induced improvement in the &quot;leg&quot; skill improvement in stroke survivors as well as in older healthy adults. The investigators will answer the question: &quot;Do stroke survivors improve leg skill learning at a comparable rate as healthy young and older adults after brain stimulation &quot;transcranial direct current stimulation&quot; (tDCS)?&quot;</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Effects of brain stimulation on functional improvements</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>To determine the effect of brain stimulation (tDCS) on functional improvements in stroke survivors. Specifically, the investigators will compare stepping reaction time, cortical neuronal activity, peripheral nerve activity, and walking function in the stroke survivors before and after tDCS, and also compared these findings with results from healthy adults. The investigators will answer the question: &quot;Do stroke survivors shorten stepping reaction time and improve leg muscle activation and gait performance after tDCS, and these improvements are at a similar rate as compared to data collected from healthy young and older adults?&quot;</description>
  </arm_group>
  <arm_group>
    <arm_group_label>Effects of brain stimulation combined with stepping training</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>After enrolling to the study, participants with chronic stroke will be randomly assigned to one of two groups: anodal tDCS or sham tDCS groups. All subjects will then undergo a total of twelve training sessions over four weeks in which subjects will learn a novel visuomotor stepping task immediately after visuomotor learning training while 20-minute tDCS (anodal or sham stimulation) is delivered over the leg area of primary motor cortex.The investigators will measure changes in brain neuronal activity, peripheral nerve activity, and walking performance before and after a 12-session training program, and will follow up one week later.</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>Transcranial direct current stimulation (tDCS)</intervention_name>
    <description>Transcranial direct current stimulation (tDCS) is an non-invasive, low-intensity direct current stimulation. The stimulation intensity is very low (0- 2 mA) to only produce tingling sensation on the scalp. From literature, there were no serious adverse effects reported after 20-minute stimulation. The main temporary side effect is skill irritation, itching sensation at the stimulation site during or after stimulation.</description>
    <arm_group_label>Brain stimulation-induced improvements in leg skill learning</arm_group_label>
    <arm_group_label>Effects of brain stimulation combined with stepping training</arm_group_label>
    <arm_group_label>Effects of brain stimulation on functional improvements</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Healthy adults have no ongoing neurological, musculoskeletal issues.&#xD;
&#xD;
          -  Individuals with chronic stroke had medical history of a unilateral stroke occurring ≥&#xD;
             6 months prior to enrollment. MRI or CT evidence from the imaging report shown that&#xD;
             the stroke involves the corticospinal tract.&#xD;
&#xD;
          -  Individuals with chronic stroke have hemiparesis involving the lower extremity.&#xD;
&#xD;
          -  Individuals with chronic stroke have no passive range of motion limitation in&#xD;
             bilateral hips and knees. Limitation of ankle passive range of motion to 10 degrees of&#xD;
             dorsiflexion or ess.&#xD;
&#xD;
          -  Visual acuity can be corrected by glasses or contact lens to 20/20.&#xD;
&#xD;
          -  Able to walk independently with/without assistant devices for 10 meters.&#xD;
&#xD;
          -  Able to maintain standing position without any assistance for more than 30 sec.&#xD;
&#xD;
          -  Evaluation of cognitive status: Mini-mental status examination (MMSE) score ≥ 24.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  Pregnant women.&#xD;
&#xD;
          -  MRI or CT evidence of involvement of the basal ganglia or cerebellum, evidence of&#xD;
             multiple lesions, or evidence of any other brain damage or malignant neoplasm or&#xD;
             tumors.&#xD;
&#xD;
          -  Have any metal implants, cardiac pacemakers, or history of seizures.&#xD;
&#xD;
          -  Ongoing orthopedic or other neuromuscular disorders that will restrict exercise&#xD;
             training.&#xD;
&#xD;
          -  Any vestibular dysfunction or unstable angina.&#xD;
&#xD;
          -  Significant cognitive deficits (inability to follow a 2-step command) or severe&#xD;
             receptive or global aphasia*&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>21 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Shih-Chiao Tseng, PT, PhD</last_name>
    <role>Principal Investigator</role>
    <affiliation>Texas Woman's University School of Physical Therapy</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Shih-Chiao Tseng, PT, PhD</last_name>
    <phone>713-794-2309</phone>
    <email>stseng@twu.edu</email>
  </overall_contact>
  <location>
    <facility>
      <name>Texas Woman's University</name>
      <address>
        <city>Houston</city>
        <state>Texas</state>
        <zip>77030</zip>
        <country>United States</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Shih-Chiao Tseng, PT, PhD</last_name>
      <phone>703-794-2309</phone>
      <email>stseng@twu.edu</email>
    </contact>
  </location>
  <location_countries>
    <country>United States</country>
  </location_countries>
  <reference>
    <citation>Matsumoto H, Ugawa Y. Adverse events of tDCS and tACS: A review. Clin Neurophysiol Pract. 2016 Dec 21;2:19-25. doi: 10.1016/j.cnp.2016.12.003. eCollection 2017.</citation>
    <PMID>30214966</PMID>
  </reference>
  <verification_date>June 2020</verification_date>
  <study_first_submitted>June 3, 2020</study_first_submitted>
  <study_first_submitted_qc>June 16, 2020</study_first_submitted_qc>
  <study_first_posted type="Actual">June 18, 2020</study_first_posted>
  <last_update_submitted>June 16, 2020</last_update_submitted>
  <last_update_submitted_qc>June 16, 2020</last_update_submitted_qc>
  <last_update_posted type="Actual">June 18, 2020</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Texas Woman's University</investigator_affiliation>
    <investigator_full_name>Shih-Chiao Tseng</investigator_full_name>
    <investigator_title>Associate Professor</investigator_title>
  </responsible_party>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Gait Disorders, Neurologic</mesh_term>
    <mesh_term>Paraparesis, Spastic</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</sharing_ipd>
  </patient_data>
  <provided_document_section>
    <provided_document>
      <document_type>Informed Consent Form</document_type>
      <document_has_protocol>No</document_has_protocol>
      <document_has_icf>Yes</document_has_icf>
      <document_has_sap>No</document_has_sap>
      <document_date>March 4, 2020</document_date>
      <document_url>https://ClinicalTrials.gov/ProvidedDocs/51/NCT04437251/ICF_000.pdf</document_url>
    </provided_document>
  </provided_document_section>
  <pending_results>
    <submitted>September 2, 2022</submitted>
    <returned>August 2, 2023</returned>
  </pending_results>
  <!-- Results have not yet been posted for this study                                          -->
</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/NCT04437251
org study id: IRB#17592- Phase I & II
nct id: NCT04437251
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
Participants are being asked to participate in a research study conducted by Shih-Chiao
      Tseng, PT, Ph.D. at Texas Woman's University. This research study is to determine whether
      low-intensive brain stimulation can enhance learning of a leg movement task. The
      investigators also want to know if brain stimulation can improve the nerve function and
      walking performance. Our goal is to understand any relationship between brain stimulation and
      overall movement control improvement. Participants have been invited to join this research if
      they have had a stroke before or they are healthy adults aged 21 years or older. Research
      evidence shows stroke can induce permanent brain damage and therefore may cause a person to
      have trouble learning a new task. This in turn may significantly impact the recovery of motor
      function in stroke survivors. In addition, the investigators also want to know how a healthy
      person learns this new leg task and see if her/his learning pattern differs from a stroke
      survivor.

      This study comprises two phases: Phase I study investigates short-term effects of brain
      stimulation on leg skill learning and only requires two visits to TWU. The total time
      commitment for Phase I study will be about 6.5 hours, 3.5 hours on the first visit and three
      hours on the second visit; Phase II study is an expanded version of Phase I study to
      investigate long-term effects of brain stimulation on leg skill learning and requires to
      complete 12 visits of exercise training paired with brain stimulation over a four-week period
      and additional one visit for follow-up test. The total time commitment for Phase II study
      will be about 20 hours, a total of 18 hours for 12 exercise training sessions and two hours
      for a follow-up test. The investigators hypothesize that people with chronic stroke will show
      a slower rate of acquiring this leg skill as compared to healthy adults. The investigators
      also hypothesize that co-applying brain stimulation with 12 sessions of exercise training
      will enhance skill learning of this leg task for people with chronic stroke and this
      12-session exercise program may exert beneficial influences on the nerve function and leg
      muscle activation, and consequentially improve motor control for walking.
This study will take place at Texas Woman's University (TWU)-Houston campus and include two
      phases: Phase I involves a single-intervention study and Phase II involves a four-week
      intervention study. After enrolling to the study, participants can choose to only participate
      in the Phase I study or choose to participate in both Phase I and Phase II studies.

      Phase I Study - participants will be asked to complete two visits, 1-14 days apart. It will
      take about a total of 6.5 hours of their time to complete all tests (3.5 hours for the first
      visit and 3 hours for the second visit, two visits). Participants will need to wear
      short-sleeve t-shirt, shorts, and a pair of sneakers for testing. During the first visit, the
      investigators will measure how well the nervous system works and how well the individual
      walks (see details as follows). If participants have had a stroke before, on the first visit
      the investigators will do some tests on to make sure participants have good feeling, balance,
      and motor responses in their legs. If all tests are good, participants will fill out a form
      asking about their medical history. If participants have not had a stroke, the investigators
      will ask a few questions to make sure participants do not have any medical issues.

      Next, the investigators will ask participants to learn a leg movement task at each visit. The
      task is to control and move a computer cursor from a start location to one of three targets
      displayed on the computer monitor. Participants will need to make forward, rightward or
      leftward foot movements to guide the cursor to one of the targets. The task itself is similar
      to the daily computer task performed by a hand mouse. In each visit, it will take
      approximately a total of 45 minutes to complete a set of leg reaching task. Several
      one-minute rest breaks will be provided as needed during test. Participants will then be
      asked to come back for the second visit within 1-14 days later to repeat the same task.
      Throughout practice, participants will learn how to control the cursor using their feet. So
      the investigators can compare the learning capacity over two visits to best indicate the
      change in the learning capacity over time.

      The investigators also want to know if participants can learn this motor skill faster with
      cutaneous brain stimulation. Participants will receive weak electrical brain stimulation for
      20 minutes during leg skill learning. The brain stimulation device that the investigators
      used is similar to the commercial product seen in the TV/magazine, called "transcutaneous
      electrical Nerve stimulation" in which electrical current is delivered by electrodes for pain
      relief and muscle stimulation. In this study, two electrodes, one placed on the top of the
      scalp and one placed on the forehead, will deliver weak electrical current for 20 minutes.
      Because the investigators set the current intensity at a very low level, it will not cause
      any muscle twitches and participants may only feel little tingling sensation in the first 10
      seconds. Most of the time, participants likely become accustomed to the stimulation and no
      longer feel the stimulation throughout the rest of the session.

      Phase II Study - This study is an expanded version of Phase I study. Participants will be
      asked to complete 12 visits of exercise training paired with brain stimulation over a
      four-week period. It will take about a total of 18 hours of the time to complete all training
      sessions (1.5 hour for each visit/training for a total of 12 visits). Participants will need
      to wear short-sleeve t-shirt, shorts, and a pair of sneakers for training. Before and after
      four-week training, the investigators will measure how well the nervous system works and how
      well the participant walks (see details as follows). One week after completion of four-week
      training, participants will be asked to come back to repeat the same tests. The investigators
      will compare changes in the learning capacity and motor function before and after four-week
      training, and at one week after completion of training to best indicate permanent changes in
      the learning capacity and motor function over time.

      During each visit, the investigators will ask participants to continue learning a leg
      movement task same as the Phase I study. The investigators will also ask participants to
      learn a similar leg task, call stepping task during standing. This stepping task is very
      similar to the leg task in the Phase I study, but is a more advanced task that requires a
      good standing balance. The task is to control a computerized marker attached to the foot and
      move a computer cursor from a start location to one of three targets displayed on the
      computer monitor. Participants will need to make forward, rightward or leftward stepping
      movements to guide the cursor to one of the targets. The task itself is similar to stepping
      motion during walking. In each visit, it will take approximately a total of 1.5 hour to
      complete two sets of leg task training during sitting and standing. Same brain stimulation
      used in the Phase I study (see above) will be delivered during the middle of the exercise
      training. Several one-minute rest breaks will be provided as needed during training.
      Participants will then be asked to come to the laboratory three times per week for four weeks
      in order to complete 12 training sessions.

      Outcome measures - For the measurement of brain activity, the investigators will put a
      recording electrode on the calf muscle in one leg. Five low-intensity brain stimulation will
      be delivered to the scalp to trigger the motor responses. Most of the time, participants will
      feel single muscle twitch due to the stimulation. It would take a total of 10 minutes to
      finish data collection. For the measurement of nerve activity, the investigators will put a
      recording electrode on the calf muscle in one leg. Low-intensity electrical stimulation will
      be delivered to a nerve behind the knee to trigger motor responses. A series of small tendon
      vibration stimuli will be delivered during electrical stimulation to determine the
      sensitivity of the nerve. Most of the time, participants will feel nothing or just light
      tingling sensation in the stimulated area. It would take a total of 40 minutes to finish data
      collection. Several one-minute rest breaks will be provided as needed during test. For the
      measurement of walking, the investigators will put sticky markers on both legs and ask
      participants to walk normally across a 10-meter walkway for five trials. It would take
      approximately a total of 30 minutes to finish data collection. Several one-minute rest breaks
      will be provided as needed during test. For the stepping reaction time test, subjects will
      stand on the force plates and will be instructed to step forward onto a target marked on the
      floor as soon as they sense electrical stimulation delivered to the posterior of the leg. It
      would take approximately a total of 40 minutes to finish data collection. Several one-minute
      rest breaks will be provided as needed during test.
allocation: Randomized
intervention model: Parallel Assignment
intervention model description: This study is a double-blinded, randomized controlled study in which participants will be randomly assigned into one of two brain stimulation groups (sham or real brain stimulation) while being evaluated for their ability of learning a leg task in a single session (phase I), and receiving a 12-session leg exercise training program.
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
masking description: The participants will not be informed about their group assignments while learning a leg task. The testers who are conducting neurological and walking assessments before and after training will also be blinded from the group assignments.
measure: Changes in stepping reaction time (Phase I)
time frame: Measure changes in the reaction time before, immediately after (i.e. within a minute), and 30 minutes after a single session of brain stimulation.
description: Calculate the time duration for the central nervous system to process information and produce a stepping action.
measure: Changes in stepping reaction time (Phase II)
time frame: Measure changes in reaction time before training, up to 24 hours after the completion of a 12-session training program, and one week after the completion of a 12-session training program.
description: Calculate the time duration for the central nervous system to process information and produce a stepping action.
measure: Changes in walking performance (Phase I)
time frame: Measure changes in the walking speed before, immediately after (i.e. within a minute), and 30 minutes after a single session of brain stimulation.
description: Measure walking speed (meters/second) during ground walking at a self-selected speed.
measure: Changes in walking performance (Phase I)
time frame: Measure changes in the step length symmetry before, immediately after (i.e. within a minute), and 30 minutes after a single session of brain stimulation.
description: Measure step length (centimeters) symmetry (left/right) during ground walking at a self-selected speed.
measure: Changes in walking performance (Phase II)
time frame: Measure changes in the walking speed before training, up to 24 hours after the completion of a 12-session training program, and one week after the completion of a 12-session training program.
description: Measure walking speed (meters/second) during ground walking at a self-selected speed.
measure: Changes in walking performance (Phase II)
time frame: Measure changes in the step length symmetry before training, up to 24 hours after the completion of a 12-session training program, and one week after the completion of a 12-session training program.
description: Measure step length symmetry (left/right) during ground walking at a self-selected speed.
measure: Changes in nerve function (Phase I)
time frame: Measure changes in the nerve function before, immediately after (i.e. within a minute), and 30 minutes after a single session of brain stimulation.
description: Place a surface electrode on the calf muscle to record muscle activation triggered by electrical stimulation delivered to the motor neurons in the lesioned motor cortex and tibial nerve on the paretic leg to qualify changes in neuronal activity in the primary cortex and in the spinal cord before and after brain stimulation (tDCS).
measure: Changes in nerve function (Phase II)
time frame: Measure changes in the nerve function before training, up to 24 hours after the completion of a 12-session training program), and one week after the completion of a 12-session training program.
description: Place a surface electrode on the calf muscle to record muscle activation triggered by electrical stimulation delivered to the motor neurons in the lesioned motor cortex and tibial nerve on the paretic leg to qualify changes in neuronal activity in the primary cortex and in the spinal cord before and after brain stimulation (tDCS).
measure: Mini-mental State Examination (Phase I)
time frame: Administer Mini-mental State Examination at the first visit before testing and training
description: A standardized questionnaires to evaluate the cognitive function consisting of 11 items with a possible summed score ranging from zero to 30. The most widely accepted and frequently used cutoff score for the MMSE is 23, with scores of 23 or lower indicating the presence of cognitive impairment. A higher score means a better cognitive function.
measure: Mini-mental State Examination (Phase II)
time frame: Administer Mini-mental State Examination at the first visit before testing and training
description: A standardized questionnaires to evaluate the cognitive function consisting of 11 items with a possible summed score ranging from zero to 30. The most widely accepted and frequently used cutoff score for the MMSE is 23, with scores of 23 or lower indicating the presence of cognitive impairment.A higher score means a better cognitive function.
measure: Fugl-Meyer Lower Extremity Function Assessment (Phase I)
time frame: Administer Fugl-Meyer Lower Extremity Function Assessment at the first visit before testing and training
description: A standardized questionnaires to evaluate the lower extremity motor function consisting of movement, coordination, and reflex assessments at hip, knee, and ankle. Possible summed scores range from zero to 34. Higher scores indicate higher and better motor function.
measure: Fugl-Meyer Lower Extremity Function Assessment (Phase II)
time frame: Administer Fugl-Meyer Lower Extremity Function Assessment at the first visit before testing and training
description: A standardized questionnaires to evaluate the lower extremity motor function consisting of movement, coordination, and reflex assessments at hip, knee, and ankle. Possible summed scores range from zero to 34. Higher scores indicate higher and better motor function.
arm group label: Brain stimulation-induced improvements in leg skill learning
arm group type: Experimental
description: To examine the degree of stimulation-induced improvements in learning capacity between three groups: stroke group, healthy young group, and healthy older group. Up to date, most studies have investigated the effects of brain stimulation on hand skill improvements in healthy young adults; little is known about stimulation-induced improvement in the "leg" skill improvement in stroke survivors as well as in older healthy adults. The investigators will answer the question: "Do stroke survivors improve leg skill learning at a comparable rate as healthy young and older adults after brain stimulation "transcranial direct current stimulation" (tDCS)?"
arm group label: Effects of brain stimulation on functional improvements
arm group type: Experimental
description: To determine the effect of brain stimulation (tDCS) on functional improvements in stroke survivors. Specifically, the investigators will compare stepping reaction time, cortical neuronal activity, peripheral nerve activity, and walking function in the stroke survivors before and after tDCS, and also compared these findings with results from healthy adults. The investigators will answer the question: "Do stroke survivors shorten stepping reaction time and improve leg muscle activation and gait performance after tDCS, and these improvements are at a similar rate as compared to data collected from healthy young and older adults?"
arm group label: Effects of brain stimulation combined with stepping training
arm group type: Sham Comparator
description: After enrolling to the study, participants with chronic stroke will be randomly assigned to one of two groups: anodal tDCS or sham tDCS groups. All subjects will then undergo a total of twelve training sessions over four weeks in which subjects will learn a novel visuomotor stepping task immediately after visuomotor learning training while 20-minute tDCS (anodal or sham stimulation) is delivered over the leg area of primary motor cortex.The investigators will measure changes in brain neuronal activity, peripheral nerve activity, and walking performance before and after a 12-session training program, and will follow up one week later.
intervention type: Device
intervention name: Transcranial direct current stimulation (tDCS)
description: Transcranial direct current stimulation (tDCS) is an non-invasive, low-intensity direct current stimulation. The stimulation intensity is very low (0- 2 mA) to only produce tingling sensation on the scalp. From literature, there were no serious adverse effects reported after 20-minute stimulation. The main temporary side effect is skill irritation, itching sensation at the stimulation site during or after stimulation.
arm group label: Brain stimulation-induced improvements in leg skill learning
arm group label: Effects of brain stimulation combined with stepping training
arm group label: Effects of brain stimulation on functional improvements
criteria: 
gender: All
minimum age: 21 Years
maximum age: 90 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Shih-Chiao Tseng, PT, PhD
role: Principal Investigator
affiliation: Texas Woman's University School of Physical Therapy
last name: Shih-Chiao Tseng, PT, PhD
phone: 713-794-2309
email: stseng@twu.edu
facility: 
status: Recruiting
contact: 
country: United States
citation: Matsumoto H, Ugawa Y. Adverse events of tDCS and tACS: A review. Clin Neurophysiol Pract. 2016 Dec 21;2:19-25. doi: 10.1016/j.cnp.2016.12.003. eCollection 2017.
PMID: 30214966
responsible party type: Principal Investigator
investigator affiliation: Texas Woman's University
investigator full name: Shih-Chiao Tseng
investigator title: Associate Professor
mesh term: Stroke
mesh term: Gait Disorders, Neurologic
mesh term: Paraparesis, Spastic
sharing ipd: No
provided document: 
submitted: September 2, 2022
returned: August 2, 2023