<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/NCT03012204</url>
  </required_header>
  <id_info>
    <org_study_id>121-2016010</org_study_id>
    <nct_id>NCT03012204</nct_id>
  </id_info>
  <brief_title>Comparing Effects of Various Combinations of 6 Hertz(Hz) rTMS &amp; LFrTMS on Motor Recovery Due to Cerebrovascular Disease</brief_title>
  <official_title>Series Study About the rTMS Effects on the Recovery of Limb Motor Dysfunction Due to Cerebral Vascular Disease, Part 1: Comparing the Effects of Various Combinations Between 6 Hertz(Hz) rTMS &amp; LFrTMS.</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Beijing Hospital</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Beijing Hospital</source>
  <oversight_info>
    <has_dmc>Yes</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>
      To compare the effects of various combinations between 6 hertz(Hz) rTMS &amp; LFrTMS on the limb&#xD;
      motor dysfunction due to cerebral vascular disease.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      It is the basic principle for functional recovery after cerebrovascular disease to restore&#xD;
      the original balance in reciprocal inhibition between affected hemisphere and unaffected&#xD;
      hemisphere.&#xD;
&#xD;
      repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuroplastic technique&#xD;
      rebalancing interhemispheric competition after stroke. Low frequency rTMS (LFrTMS) on&#xD;
      contralesional hemisphere or high frequency rTMS (HFrTMS) on lesional hemisphere might be the&#xD;
      basic choice.&#xD;
&#xD;
      6 hertz(Hz) primed LFrTMS on lesional primary motor cortex has the stronger effect than&#xD;
      LFrTMS alone does on one hand; the other newly-developed combination, i.e. HFrTMS on lesional&#xD;
      primary motor cortex and LFrTMS on contralesional primary motor cortex might also be more&#xD;
      effective than they do respectively on the other hand.&#xD;
&#xD;
      The main aim of our research is to find out which combination is better by considering both&#xD;
      safety and efficiency.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">February 16, 2017</start_date>
  <completion_date type="Anticipated">December 2018</completion_date>
  <primary_completion_date type="Anticipated">December 2018</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 (Participant, Outcomes Assessor)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Fugl-Meyer assessment (FMA)</measure>
    <time_frame>1) Before treatment (Baseline); 2) Change from Baseline FMA at the 1st workday after the last treatment; 3) Change from Baseline FMA at the 28th natural day after the last treatment</time_frame>
    <description>Score of Fugl-Meyer assessment</description>
  </primary_outcome>
  <primary_outcome>
    <measure>Simple Test for Evaluating Hand Function (STEF)</measure>
    <time_frame>1) Before treatment (Baseline); 2) Change from Baseline STEF at the 1st workday after the last treatment; 3) Change from Baseline STEF at the 28th natural day after the last treatment</time_frame>
    <description>Score of Simple Test for Evaluating Hand Function</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>National Institute of Health Stroke Scale (NIHSS)</measure>
    <time_frame>1) Before treatment (Baseline); 2) Change from Baseline NIHSS at the 1st workday after the last treatment; 3) Change from Baseline NIHSS at the 28th natural day after the last treatment</time_frame>
    <description>Score of National Institute of Health Stroke Scale</description>
  </secondary_outcome>
  <number_of_arms>4</number_of_arms>
  <enrollment type="Anticipated">120</enrollment>
  <condition>Cerebrovascular Disease</condition>
  <arm_group>
    <arm_group_label>combined rTMS at both M1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>combined rTMS at both M1: sham 6 hertz(Hz) rTMS on unaffected M1 / real 1 Hz rTMS on unaffected M1 / real 6 Hz rTMS on affected M1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>real primed LFrTMS at unaffected M1</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>real primed LFrTMS at unaffected M1: real 6 hertz(Hz) rTMS on unaffected M1 / real 1 Hz rTMS on unaffected M1 / sham 6 Hz rTMS on affected M1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>real LFrTMS at unaffected M1</arm_group_label>
    <arm_group_type>Active Comparator</arm_group_type>
    <description>real LFrTMS at unaffected M1: sham 6 hertz(Hz) rTMS on unaffected M1 / real 1 Hz rTMS on unaffected M1 / sham 6 Hz rTMS on affected M1</description>
  </arm_group>
  <arm_group>
    <arm_group_label>all sham stimulation</arm_group_label>
    <arm_group_type>Sham Comparator</arm_group_type>
    <description>all sham stimulation： sham 6 hertz(Hz) rTMS on unaffected M1 / sham 1 Hz rTMS on unaffected M1 /sham 6 Hz rTMS on affected M1</description>
  </arm_group>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>real LFrTMS at unaffected M1</intervention_name>
    <description>Compare the effect of LFrTMS at unaffected M1 to that of all sham stimulation on motor rehabilitation after cerebrovascular disease .&#xD;
rTMS: Repetitive Transcranial Magnetic Stimulation. Combination Elements: ①6 hertz(Hz) rTMS at unaffected M1 before LFrTMS at unaffected M1 ;②6 Hz rTMS at affected M1;③1 Hz rTMS at unaffected M1.&#xD;
The four groups are the combinations of real or sham ①/②/③.</description>
    <arm_group_label>real LFrTMS at unaffected M1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>real primed LFrTMS at unaffected M1</intervention_name>
    <description>Compare the effect of primed LFrTMS at unaffected M1 to that of LFrTMS at unaffected M1 on motor rehabilitation after cerebrovascular disease .&#xD;
rTMS: Repetitive Transcranial Magnetic Stimulation. Combination Elements: ①6 hertz(Hz) rTMS at unaffected M1 before LFrTMS at unaffected M1 ;②6 Hz rTMS at affected M1;③1 Hz rTMS at unaffected M1.&#xD;
The four groups are the combinations of real or sham ①/②/③.</description>
    <arm_group_label>real primed LFrTMS at unaffected M1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>combined rTMS at both M1</intervention_name>
    <description>Compare the effect of combined rTMS at both M1 to that of primed LFrTMS at unaffected M1 on motor rehabilitation after cerebrovascular disease .&#xD;
rTMS: Repetitive Transcranial Magnetic Stimulation. Combination Elements: ①6 hertz(Hz) rTMS at unaffected M1 before LFrTMS at unaffected M1 ;②6 Hz rTMS at affected M1;③1 Hz rTMS at unaffected M1.&#xD;
The four groups are the combinations of real or sham ①/②/③.</description>
    <arm_group_label>combined rTMS at both M1</arm_group_label>
  </intervention>
  <intervention>
    <intervention_type>Device</intervention_type>
    <intervention_name>all sham stimulation</intervention_name>
    <description>used as controls to eliminate the placebo effect of all kinds of combinated rTMS</description>
    <arm_group_label>all sham stimulation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          -  Aged from 30 to 90 years;&#xD;
&#xD;
          -  Newly onset cerebral infarction or brain hemorrhage confirmed by MRI or CT;&#xD;
&#xD;
          -  the disease duration is less than 20 weeks when recruited into the trial;&#xD;
&#xD;
          -  no existence of limb motor dysfunction before this onset, and new occurrence of&#xD;
             unilateral limb motor dysfunction after this onset;&#xD;
&#xD;
          -  the physical and mental condition are good enough to cooperate with the assessment and&#xD;
             treatment;&#xD;
&#xD;
          -  the NIHSS score: total 5-20,1a,1b,1c=0;&#xD;
&#xD;
          -  the subject or legal guardian sign the consent form.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          -  during pregnancy;&#xD;
&#xD;
          -  with skull defect;&#xD;
&#xD;
          -  with metal implants, cardiac pacemaker, cochlear implantation;&#xD;
&#xD;
          -  epileptiform discharge in EEG.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>90 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Li Zhuang, M.D.</last_name>
    <role>Principal Investigator</role>
    <affiliation>Beijing Hospital, National Center of Gerontology, China</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Jin Xing, M.D.</last_name>
    <phone>+86-13521278542</phone>
    <email>zhuanglixingjin@163.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Xinxin Ma, M.D</last_name>
    <phone>+86-15901043667</phone>
    <email>zhuanglixingjin@163.com</email>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Beijing Hospital, National Center of Gerontology</name>
      <address>
        <city>Beijing</city>
        <state>Beijing</state>
        <zip>100730</zip>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Xin Wang</last_name>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Sung WH, Wang CP, Chou CL, Chen YC, Chang YC, Tsai PY. Efficacy of coupling inhibitory and facilitatory repetitive transcranial magnetic stimulation to enhance motor recovery in hemiplegic stroke patients. Stroke. 2013 May;44(5):1375-82. doi: 10.1161/STROKEAHA.111.000522. Epub 2013 Mar 26.</citation>
    <PMID>23532011</PMID>
  </reference>
  <reference>
    <citation>Wang CP, Tsai PY, Yang TF, Yang KY, Wang CC. Differential effect of conditioning sequences in coupling inhibitory/facilitatory repetitive transcranial magnetic stimulation for poststroke motor recovery. CNS Neurosci Ther. 2014 Apr;20(4):355-63. doi: 10.1111/cns.12221. Epub 2014 Jan 15.</citation>
    <PMID>24422912</PMID>
  </reference>
  <reference>
    <citation>Carey JR, Anderson DC, Gillick BT, Whitford M, Pascual-Leone A. 6-Hz primed low-frequency rTMS to contralesional M1 in two cases with middle cerebral artery stroke. Neurosci Lett. 2010 Jan 29;469(3):338-42. doi: 10.1016/j.neulet.2009.12.023. Epub 2009 Dec 18.</citation>
    <PMID>20026185</PMID>
  </reference>
  <reference>
    <citation>Cassidy JM, Chu H, Anderson DC, Krach LE, Snow L, Kimberley TJ, Carey JR. A Comparison of Primed Low-frequency Repetitive Transcranial Magnetic Stimulation Treatments in Chronic Stroke. Brain Stimul. 2015 Nov-Dec;8(6):1074-84. doi: 10.1016/j.brs.2015.06.007. Epub 2015 Jun 22.</citation>
    <PMID>26198365</PMID>
  </reference>
  <reference>
    <citation>Carey JR, Evans CD, Anderson DC, Bhatt E, Nagpal A, Kimberley TJ, Pascual-Leone A. Safety of 6-Hz primed low-frequency rTMS in stroke. Neurorehabil Neural Repair. 2008 Mar-Apr;22(2):185-92. doi: 10.1177/1545968307305458. Epub 2007 Sep 17.</citation>
    <PMID>17876070</PMID>
  </reference>
  <verification_date>March 2017</verification_date>
  <study_first_submitted>January 4, 2017</study_first_submitted>
  <study_first_submitted_qc>January 4, 2017</study_first_submitted_qc>
  <study_first_posted type="Estimate">January 6, 2017</study_first_posted>
  <last_update_submitted>March 14, 2017</last_update_submitted>
  <last_update_submitted_qc>March 14, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">March 15, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Beijing Hospital</investigator_affiliation>
    <investigator_full_name>ZHUANG Li, MD</investigator_full_name>
    <investigator_title>Chief Physician</investigator_title>
  </responsible_party>
  <keyword>Cerebrovascular Disease</keyword>
  <keyword>Repetitive Transcranial Magnetic Stimulation</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Cerebrovascular Disorders</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>Undecided</sharing_ipd>
  </patient_data>
  <!-- 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/NCT03012204
org study id: 121-2016010
nct id: NCT03012204
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
To compare the effects of various combinations between 6 hertz(Hz) rTMS & LFrTMS on the limb
      motor dysfunction due to cerebral vascular disease.
It is the basic principle for functional recovery after cerebrovascular disease to restore
      the original balance in reciprocal inhibition between affected hemisphere and unaffected
      hemisphere.

      repetitive transcranial magnetic stimulation (rTMS) is a noninvasive neuroplastic technique
      rebalancing interhemispheric competition after stroke. Low frequency rTMS (LFrTMS) on
      contralesional hemisphere or high frequency rTMS (HFrTMS) on lesional hemisphere might be the
      basic choice.

      6 hertz(Hz) primed LFrTMS on lesional primary motor cortex has the stronger effect than
      LFrTMS alone does on one hand; the other newly-developed combination, i.e. HFrTMS on lesional
      primary motor cortex and LFrTMS on contralesional primary motor cortex might also be more
      effective than they do respectively on the other hand.

      The main aim of our research is to find out which combination is better by considering both
      safety and efficiency.
allocation: Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: Double (Participant, Outcomes Assessor)
measure: Fugl-Meyer assessment (FMA)
time frame: 1) Before treatment (Baseline); 2) Change from Baseline FMA at the 1st workday after the last treatment; 3) Change from Baseline FMA at the 28th natural day after the last treatment
description: Score of Fugl-Meyer assessment
measure: Simple Test for Evaluating Hand Function (STEF)
time frame: 1) Before treatment (Baseline); 2) Change from Baseline STEF at the 1st workday after the last treatment; 3) Change from Baseline STEF at the 28th natural day after the last treatment
description: Score of Simple Test for Evaluating Hand Function
measure: National Institute of Health Stroke Scale (NIHSS)
time frame: 1) Before treatment (Baseline); 2) Change from Baseline NIHSS at the 1st workday after the last treatment; 3) Change from Baseline NIHSS at the 28th natural day after the last treatment
description: Score of National Institute of Health Stroke Scale
arm group label: combined rTMS at both M1
arm group type: Experimental
description: combined rTMS at both M1: sham 6 hertz(Hz) rTMS on unaffected M1 / real 1 Hz rTMS on unaffected M1 / real 6 Hz rTMS on affected M1
arm group label: real primed LFrTMS at unaffected M1
arm group type: Experimental
description: real primed LFrTMS at unaffected M1: real 6 hertz(Hz) rTMS on unaffected M1 / real 1 Hz rTMS on unaffected M1 / sham 6 Hz rTMS on affected M1
arm group label: real LFrTMS at unaffected M1
arm group type: Active Comparator
description: real LFrTMS at unaffected M1: sham 6 hertz(Hz) rTMS on unaffected M1 / real 1 Hz rTMS on unaffected M1 / sham 6 Hz rTMS on affected M1
arm group label: all sham stimulation
arm group type: Sham Comparator
description: all sham stimulation： sham 6 hertz(Hz) rTMS on unaffected M1 / sham 1 Hz rTMS on unaffected M1 /sham 6 Hz rTMS on affected M1
intervention type: Device
intervention name: real LFrTMS at unaffected M1
description: Compare the effect of LFrTMS at unaffected M1 to that of all sham stimulation on motor rehabilitation after cerebrovascular disease .
rTMS: Repetitive Transcranial Magnetic Stimulation. Combination Elements: ①6 hertz(Hz) rTMS at unaffected M1 before LFrTMS at unaffected M1 ;②6 Hz rTMS at affected M1;③1 Hz rTMS at unaffected M1.
The four groups are the combinations of real or sham ①/②/③.
arm group label: real LFrTMS at unaffected M1
intervention type: Device
intervention name: real primed LFrTMS at unaffected M1
description: Compare the effect of primed LFrTMS at unaffected M1 to that of LFrTMS at unaffected M1 on motor rehabilitation after cerebrovascular disease .
rTMS: Repetitive Transcranial Magnetic Stimulation. Combination Elements: ①6 hertz(Hz) rTMS at unaffected M1 before LFrTMS at unaffected M1 ;②6 Hz rTMS at affected M1;③1 Hz rTMS at unaffected M1.
The four groups are the combinations of real or sham ①/②/③.
arm group label: real primed LFrTMS at unaffected M1
intervention type: Device
intervention name: combined rTMS at both M1
description: Compare the effect of combined rTMS at both M1 to that of primed LFrTMS at unaffected M1 on motor rehabilitation after cerebrovascular disease .
rTMS: Repetitive Transcranial Magnetic Stimulation. Combination Elements: ①6 hertz(Hz) rTMS at unaffected M1 before LFrTMS at unaffected M1 ;②6 Hz rTMS at affected M1;③1 Hz rTMS at unaffected M1.
The four groups are the combinations of real or sham ①/②/③.
arm group label: combined rTMS at both M1
intervention type: Device
intervention name: all sham stimulation
description: used as controls to eliminate the placebo effect of all kinds of combinated rTMS
arm group label: all sham stimulation
criteria: 
gender: All
minimum age: 30 Years
maximum age: 90 Years
healthy volunteers: No
last name: Li Zhuang, M.D.
role: Principal Investigator
affiliation: Beijing Hospital, National Center of Gerontology, China
last name: Jin Xing, M.D.
phone: +86-13521278542
email: zhuanglixingjin@163.com
last name: Xinxin Ma, M.D
phone: +86-15901043667
email: zhuanglixingjin@163.com
facility: 
status: Recruiting
contact: 
country: China
citation: Sung WH, Wang CP, Chou CL, Chen YC, Chang YC, Tsai PY. Efficacy of coupling inhibitory and facilitatory repetitive transcranial magnetic stimulation to enhance motor recovery in hemiplegic stroke patients. Stroke. 2013 May;44(5):1375-82. doi: 10.1161/STROKEAHA.111.000522. Epub 2013 Mar 26.
PMID: 23532011
citation: Wang CP, Tsai PY, Yang TF, Yang KY, Wang CC. Differential effect of conditioning sequences in coupling inhibitory/facilitatory repetitive transcranial magnetic stimulation for poststroke motor recovery. CNS Neurosci Ther. 2014 Apr;20(4):355-63. doi: 10.1111/cns.12221. Epub 2014 Jan 15.
PMID: 24422912
citation: Carey JR, Anderson DC, Gillick BT, Whitford M, Pascual-Leone A. 6-Hz primed low-frequency rTMS to contralesional M1 in two cases with middle cerebral artery stroke. Neurosci Lett. 2010 Jan 29;469(3):338-42. doi: 10.1016/j.neulet.2009.12.023. Epub 2009 Dec 18.
PMID: 20026185
citation: Cassidy JM, Chu H, Anderson DC, Krach LE, Snow L, Kimberley TJ, Carey JR. A Comparison of Primed Low-frequency Repetitive Transcranial Magnetic Stimulation Treatments in Chronic Stroke. Brain Stimul. 2015 Nov-Dec;8(6):1074-84. doi: 10.1016/j.brs.2015.06.007. Epub 2015 Jun 22.
PMID: 26198365
citation: Carey JR, Evans CD, Anderson DC, Bhatt E, Nagpal A, Kimberley TJ, Pascual-Leone A. Safety of 6-Hz primed low-frequency rTMS in stroke. Neurorehabil Neural Repair. 2008 Mar-Apr;22(2):185-92. doi: 10.1177/1545968307305458. Epub 2007 Sep 17.
PMID: 17876070
responsible party type: Principal Investigator
investigator affiliation: Beijing Hospital
investigator full name: ZHUANG Li, MD
investigator title: Chief Physician
mesh term: Cerebrovascular Disorders
sharing ipd: Undecided