<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/NCT03828435</url>
  </required_header>
  <id_info>
    <org_study_id>104-2292A3</org_study_id>
    <nct_id>NCT03828435</nct_id>
  </id_info>
  <brief_title>Individualized rTMS Protocol for Stroke Recovery</brief_title>
  <official_title>Development and Efficacy Evaluation of Individualized rTMS Protocol for Stroke Recovery</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Chang Gung Memorial Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Chang Gung Memorial Hospital</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This study aims to develop individualized therapeutic protocol to improve stroke recovery and&#xD;
      fits the scheme of Mechanisms, biomarkers, and treatment strategies for stroke, aging, and&#xD;
      Parkinson's disease by advanced EEG analysis and transcranial magnetic stimulation technique.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It has long been a challenge to promote the recovery after stroke. So far, rehabilitation has&#xD;
      been the most evident way for this purpose, while pharmacological approaches have done very&#xD;
      little.&#xD;
&#xD;
      However, the unsatisfied results urge us to recognize the need of new therapeutic solutions&#xD;
      for stroke recovery. In the past few years, the development of non-invasive brain stimulation&#xD;
      techniques, which are capable of altering the brain excitability through plasticity-like&#xD;
      mechanisms for up to an hour or so, lead to the expectation of improving the recovery of&#xD;
      stroke and other neurological disorders by manipulation neuroplasticity. Nevertheless, even&#xD;
      with the help of brain stimulation, the results in stroke recovery are diverse and limited,&#xD;
      although most studies agree that non-invasive brain stimulation, including repetitive&#xD;
      transcranial magnetic stimulation (rTMS) is beneficial to the recovery after stroke.&#xD;
&#xD;
      Therefore, it is an important topic to ameliorate the recipe of brain stimulation for stroke&#xD;
      recovery to improve its efficiency and efficacy. Facing this challenge, the investigators&#xD;
      designed this study to develop individualized rTMS protocol for stroke recovery, to verify&#xD;
      the predictor of stroke outcome discovered by DCM and to explore factors that cause the&#xD;
      variability of rTMS. Based on our recent findings that revealed key patterns of stroke&#xD;
      recovery base in EEG-based EEG based dynamic causal modelling (DCM), the individualize TMS&#xD;
      protocol will be developed. The investigators will first apply different protocols of rTMS&#xD;
      given to a variety of locations within the motor network to evaluate their effects on the DCM&#xD;
      network. The results will be used for selecting proper rTMS protocols for stroke patients&#xD;
      based on their DCM results. The effect of the individualized rTMS protocol will be tested in&#xD;
      a small group of patient first. Then the longer therapeutic effect of the protocol will be&#xD;
      assessed in a larger patient group under a double-blinded randomized control basis. With the&#xD;
      help of this project, the investigators will be able to understand how different protocols of&#xD;
      rTMS given to a variety of locations within the motor network affect the DCM network. Such&#xD;
      information will be useful for developing individualized rTMS protocol for not only stroke&#xD;
      therapy in the present study, but also other neurological disorders, e.g. Parkinson's disease&#xD;
      and dystonia, in the further studies.&#xD;
&#xD;
      Furthermore, the investigators expect that the patients stimulated with rTMS using the&#xD;
      protocol matched to their DCM network will recover better than those treated with unmatched&#xD;
      protocol. This part of result could be further applied as a clinical application to&#xD;
      facilitate stroke recovery. The predictors for stroke recovery revealed by the DCM model will&#xD;
      also be verified in the current project. This will give us more information about the&#xD;
      accuracy of the predictors and may give us new insights for the further development of stroke&#xD;
      therapy. The investigators will further analyze EEG data and the results to provide knowledge&#xD;
      of the state-dependent effect of brain on the variability of the current forms of rTMS and&#xD;
      other noninvasive brain stimulation. This part of information will be very helpful for&#xD;
      developing the strategy for eliminating the variability of rTMS and for improving the&#xD;
      protocol of rTMS to be more powerful and efficient.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">April 2016</start_date>
  <completion_date type="Anticipated">December 2019</completion_date>
  <primary_completion_date type="Anticipated">December 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>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>Double (Investigator, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>The changes of Fugl-Meyer Assessment of Physical Performance (FM)</measure>
    <time_frame>upon recruitment, after 24 weeks of rehabilitation treatment</time_frame>
    <description>a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The changes of upper extremity performance evaluation test for the elderly (TEMPA)</measure>
    <time_frame>upon recruitment, after 24 weeks of rehabilitation treatment</time_frame>
    <description>a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia</description>
  </primary_outcome>
  <primary_outcome>
    <measure>The changes of Wolf Motor Function Test (WMFT)</measure>
    <time_frame>upon recruitment, after 24 weeks of rehabilitation treatment</time_frame>
    <description>a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia</description>
  </primary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">170</enrollment>
  <condition>Stroke</condition>
  <arm_group>
    <arm_group_label>healthy control</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>This group does not undergo any treatment . Intervention : rTMS</description>
  </arm_group>
  <arm_group>
    <arm_group_label>stroke patient</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>this group undergoes rehabilitative therapy. It is a 24-week program and stroke patients practice the physical exercise for 1 hour each time. The intensity is three times a week.&#xD;
Intervention : rTMS</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>rTMS</intervention_name>
    <description>Magnetic stimulation will be given using a hand-held figure-of-eight coil with an median winding diameter of 70 mm or a cone coil (Magstim Co., Whitland, Dyfed, UK) connected to one Magstim Rapid2 Package (Magstim Co., UK). The figure-of-eight coil will be placed tangentially to the scalp with the handle pointing backwards, which is thought to preferentially activate the corticospinal cells trans-synaptically (Kaneko et al., 1996), while the cone coil will be placed along the anterioposterior axis to induce a posterior-to-anterior current in the cortex.</description>
    <arm_group_label>healthy control</arm_group_label>
    <arm_group_label>stroke patient</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  first-ever stroke&#xD;
&#xD;
          -  in subacute stage (between 1-3 months after stroke onset)&#xD;
&#xD;
          -  monohemispheric ischemic stroke&#xD;
&#xD;
          -  able to follow the command of the shoulder flexion&#xD;
&#xD;
          -  mild to moderate paresis in the upper limb (the motor arm score of National Institute&#xD;
             of Health Stroke Scale (NIHSS) = 1 &amp; 2 out of 4, where 4 = no movement)&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  being less than 20 years or over 75 years of age&#xD;
&#xD;
          -  history of seizures or epileptiform discharges on electroencephalogram (EEG)&#xD;
&#xD;
          -  pregnancy&#xD;
&#xD;
          -  aphasia, apraxia, and concomitant neurological diseases or other severe medical&#xD;
             diseases (e.g., sepsis, malignancy, hepatic or renal failure).&#xD;
&#xD;
          -  having a pacemaker, an implanted medication pump, a metal plate in the skull, or metal&#xD;
             objects inside the eye or skull (for example after brain surgery or a shrapnel wound)&#xD;
&#xD;
          -  taking tricyclic antidepressants, neuroleptic agents and other drugs that lower the&#xD;
             seizure threshold&#xD;
&#xD;
          -  Insulin dependent diabetes&#xD;
&#xD;
          -  Thyroid disease&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>20 Years</minimum_age>
    <maximum_age>75 Years</maximum_age>
    <healthy_volunteers>Accepts Healthy Volunteers</healthy_volunteers>
  </eligibility>
  <overall_contact>
    <last_name>Ying-Zu Huang, MD, PhD</last_name>
    <phone>+886 3 3281200</phone>
    <phone_ext>3775</phone_ext>
    <email>yzhuang@cgmh.org.tw</email>
  </overall_contact>
  <location>
    <facility>
      <name>Ying-Zu Huang</name>
      <address>
        <city>Taoyuan</city>
        <zip>333</zip>
        <country>Taiwan</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Ying-Zu Huang, MD, PhD</last_name>
    </contact>
    <investigator>
      <last_name>CC Chen</last_name>
      <role>Sub-Investigator</role>
    </investigator>
  </location>
  <location_countries>
    <country>Taiwan</country>
  </location_countries>
  <verification_date>January 2019</verification_date>
  <study_first_submitted>January 27, 2016</study_first_submitted>
  <study_first_submitted_qc>January 31, 2019</study_first_submitted_qc>
  <study_first_posted type="Actual">February 4, 2019</study_first_posted>
  <last_update_submitted>January 31, 2019</last_update_submitted>
  <last_update_submitted_qc>January 31, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">February 4, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>patient</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
  </condition_browse>
  <!-- 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/NCT03828435
org study id: 104-2292A3
nct id: NCT03828435
lead sponsor: 
has dmc: Yes
This study aims to develop individualized therapeutic protocol to improve stroke recovery and
      fits the scheme of Mechanisms, biomarkers, and treatment strategies for stroke, aging, and
      Parkinson's disease by advanced EEG analysis and transcranial magnetic stimulation technique.
It has long been a challenge to promote the recovery after stroke. So far, rehabilitation has
      been the most evident way for this purpose, while pharmacological approaches have done very
      little.

      However, the unsatisfied results urge us to recognize the need of new therapeutic solutions
      for stroke recovery. In the past few years, the development of non-invasive brain stimulation
      techniques, which are capable of altering the brain excitability through plasticity-like
      mechanisms for up to an hour or so, lead to the expectation of improving the recovery of
      stroke and other neurological disorders by manipulation neuroplasticity. Nevertheless, even
      with the help of brain stimulation, the results in stroke recovery are diverse and limited,
      although most studies agree that non-invasive brain stimulation, including repetitive
      transcranial magnetic stimulation (rTMS) is beneficial to the recovery after stroke.

      Therefore, it is an important topic to ameliorate the recipe of brain stimulation for stroke
      recovery to improve its efficiency and efficacy. Facing this challenge, the investigators
      designed this study to develop individualized rTMS protocol for stroke recovery, to verify
      the predictor of stroke outcome discovered by DCM and to explore factors that cause the
      variability of rTMS. Based on our recent findings that revealed key patterns of stroke
      recovery base in EEG-based EEG based dynamic causal modelling (DCM), the individualize TMS
      protocol will be developed. The investigators will first apply different protocols of rTMS
      given to a variety of locations within the motor network to evaluate their effects on the DCM
      network. The results will be used for selecting proper rTMS protocols for stroke patients
      based on their DCM results. The effect of the individualized rTMS protocol will be tested in
      a small group of patient first. Then the longer therapeutic effect of the protocol will be
      assessed in a larger patient group under a double-blinded randomized control basis. With the
      help of this project, the investigators will be able to understand how different protocols of
      rTMS given to a variety of locations within the motor network affect the DCM network. Such
      information will be useful for developing individualized rTMS protocol for not only stroke
      therapy in the present study, but also other neurological disorders, e.g. Parkinson's disease
      and dystonia, in the further studies.

      Furthermore, the investigators expect that the patients stimulated with rTMS using the
      protocol matched to their DCM network will recover better than those treated with unmatched
      protocol. This part of result could be further applied as a clinical application to
      facilitate stroke recovery. The predictors for stroke recovery revealed by the DCM model will
      also be verified in the current project. This will give us more information about the
      accuracy of the predictors and may give us new insights for the further development of stroke
      therapy. The investigators will further analyze EEG data and the results to provide knowledge
      of the state-dependent effect of brain on the variability of the current forms of rTMS and
      other noninvasive brain stimulation. This part of information will be very helpful for
      developing the strategy for eliminating the variability of rTMS and for improving the
      protocol of rTMS to be more powerful and efficient.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Investigator, Outcomes Assessor)
measure: The changes of Fugl-Meyer Assessment of Physical Performance (FM)
time frame: upon recruitment, after 24 weeks of rehabilitation treatment
description: a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia
measure: The changes of upper extremity performance evaluation test for the elderly (TEMPA)
time frame: upon recruitment, after 24 weeks of rehabilitation treatment
description: a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia
measure: The changes of Wolf Motor Function Test (WMFT)
time frame: upon recruitment, after 24 weeks of rehabilitation treatment
description: a stroke-specific, performance-based impairment index. It is designed to assess motor functioning, balance, sensation and joint functioning in patients with post-stroke hemiplegia
arm group label: healthy control
arm group type: Experimental
description: This group does not undergo any treatment . Intervention : rTMS
arm group label: stroke patient
arm group type: Experimental
description: this group undergoes rehabilitative therapy. It is a 24-week program and stroke patients practice the physical exercise for 1 hour each time. The intensity is three times a week.
Intervention : rTMS
intervention type: Device
intervention name: rTMS
description: Magnetic stimulation will be given using a hand-held figure-of-eight coil with an median winding diameter of 70 mm or a cone coil (Magstim Co., Whitland, Dyfed, UK) connected to one Magstim Rapid2 Package (Magstim Co., UK). The figure-of-eight coil will be placed tangentially to the scalp with the handle pointing backwards, which is thought to preferentially activate the corticospinal cells trans-synaptically (Kaneko et al., 1996), while the cone coil will be placed along the anterioposterior axis to induce a posterior-to-anterior current in the cortex.
arm group label: healthy control
arm group label: stroke patient
criteria: 
gender: All
minimum age: 20 Years
maximum age: 75 Years
healthy volunteers: Accepts Healthy Volunteers
last name: Ying-Zu Huang, MD, PhD
phone: +886 3 3281200
phone ext: 3775
email: yzhuang@cgmh.org.tw
facility: 
status: Recruiting
contact: 
investigator: 
country: Taiwan
responsible party type: Sponsor
mesh term: Stroke