<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/NCT03296618</url>
  </required_header>
  <id_info>
    <org_study_id>NS2012-1</org_study_id>
    <nct_id>NCT03296618</nct_id>
  </id_info>
  <brief_title>Intracerebral Transplantation of Neural Stem Cells for the Treatment of Ischemic Stroke</brief_title>
  <official_title>Phase I Clinical Study of Intracerebral Transplantation of Neural Stem Cells for the Treatment of Ischemic Stroke</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Suzhou Neuralstem Biopharmaceuticals</agency>
      <agency_class>Industry</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Neuralstem Inc.</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>
      The study is to determine the safety of human neural stem cell transplantation for the&#xD;
      treatment of paralysis and related symptoms due to chronic motor stroke and to determine the&#xD;
      maximum tolerated dose.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a Phase I study of human neural stem cell transplantation for the treatment of&#xD;
      chronic motor stroke. This single-site, Phase I, open-label study may enroll up to 18&#xD;
      patients across 5 cohorts of ascending doses of human neural stem cells to define maximal&#xD;
      tolerated dose.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Active, not recruiting</last_known_status>
  <start_date>June 2012</start_date>
  <completion_date type="Anticipated">May 2018</completion_date>
  <primary_completion_date type="Anticipated">May 2018</primary_completion_date>
  <phase>Phase 1</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>N/A</allocation>
    <intervention_model>Single Group Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Adverse Events</measure>
    <time_frame>24 months</time_frame>
  </primary_outcome>
  <secondary_outcome>
    <measure>Clinical improvement using NIH Stroke Scale</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical improvement using Modified Rankin Scale</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical improvement using Fugl-Meyer Motor Score</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Clinical Improvement using Mini-mental State Examination</measure>
    <time_frame>12 months</time_frame>
  </secondary_outcome>
  <other_outcome>
    <measure>MRI analysis of transplant site</measure>
    <time_frame>12 months</time_frame>
  </other_outcome>
  <other_outcome>
    <measure>PET analysis of transplant site</measure>
    <time_frame>12 months</time_frame>
  </other_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Anticipated">18</enrollment>
  <condition>Ischemic Motor Stroke, Chronic</condition>
  <arm_group>
    <arm_group_label>NSI-566 neural stem cell implantation</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>NSI-566</intervention_name>
    <description>Dosing will consist of a one-time stereotactic, intracranial injection of a hNSC line, NSI-566, ranging from 1.2×107 cells to 8×107 cells, as tolerated.</description>
    <arm_group_label>NSI-566 neural stem cell implantation</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. Have the ability to understand the requirements of the study, provide written informed&#xD;
             consent, understand and provide written authorization for the use and disclosure of&#xD;
             Protected Health Information (PHI) [per Health Insurance Portability and&#xD;
             Accountability Act (HIPAA) Privacy Ruling] and comply with the study procedures&#xD;
&#xD;
          2. Men and women 30-65 years old&#xD;
&#xD;
          3. Women must have a negative serum pregnancy test and practice an acceptable method of&#xD;
             contraception or be of non-childbearing potential (post-menopausal for at least 2&#xD;
             years or who have undergone hysterectomy or oophorectomy or surgical sterilization)&#xD;
&#xD;
          4. At least 3 months but no more than 24 months from time of stroke, with a motor&#xD;
             neurological deficit&#xD;
&#xD;
          5. Documented history of completed ischemic stroke in subcortical region of MCA or&#xD;
             lenticulostriate artery with or without cortical involvement, with correlated findings&#xD;
             by MRI&#xD;
&#xD;
          6. Modified Rankin Score of 2, 3 or 4&#xD;
&#xD;
          7. FMMS score of 55 or less;&#xD;
&#xD;
          8. Two evaluations at approximately 3 weeks apart prior to surgery with less than +/- 4&#xD;
             point change in the NIHSS&#xD;
&#xD;
          9. Able and willing to meet all follow-up requirements&#xD;
&#xD;
         10. Able and willing to undergo post-physical therapy/rehabilitation&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Any disabling psychological or psychiatric disorders which may confound the study&#xD;
&#xD;
          2. History of more than one symptomatic stroke, TIAs allowed&#xD;
&#xD;
          3. History of another major neurological disease or injury&#xD;
&#xD;
          4. Cerebral infarct size &gt;8cm in any one measurement&#xD;
&#xD;
          5. Myocardial infarction within the prior 3 months&#xD;
&#xD;
          6. History of seizures or current use of antiepileptic medication&#xD;
&#xD;
          7. Receipt of any investigational drug or device within 30 days&#xD;
&#xD;
          8. Receipt of any cell infusion other than blood transfusion&#xD;
&#xD;
          9. Any concomitant medical disease or condition noted below:&#xD;
&#xD;
               1. Coagulopathy with INR &gt; 1.4 at the time of surgery&#xD;
&#xD;
               2. Panel Reactive Antibodies (PRA) &gt; 20% at initial screen&#xD;
&#xD;
               3. Active infection at the time of surgery&#xD;
&#xD;
               4. Active hypotension requiring vasopressor therapy&#xD;
&#xD;
               5. Skin breakdown over the site of surgery&#xD;
&#xD;
               6. Active or history of malignancy&#xD;
&#xD;
               7. Primary or secondary immune deficiency&#xD;
&#xD;
               8. Persistent MRI artifact that would prevent imaging pre and post-operation or&#xD;
                  unable to undergo MRI&#xD;
&#xD;
               9. Creatinine &gt;115μmol/L, liver function tests (SGOT/SGPT, Bilirubin, Alk Phos) &gt; 2x&#xD;
                  upper limit of normal, hematocrit/hemoglobin &lt; 30/10, total WBC &lt;&#xD;
                  4000/mm3,platelet count &lt;100,000/mm3, uncontrolled hypertension (systolic &gt;&#xD;
                  180mmHg or diastolic&gt; 100mmHg) or uncontrolled diabetes (defined as hemoglobin&#xD;
                  A1C&gt;8%), evidence of GI bleeding by hemoccult test,positive tuberculosis (TB&#xD;
                  test: PPD/Mantoux), hepatitis B or C, or human immunodeficiency virus (HIV)&#xD;
&#xD;
         10. Presence of any of the following conditions:&#xD;
&#xD;
               1. Current drug abuse or alcoholism&#xD;
&#xD;
               2. Unstable medical conditions&#xD;
&#xD;
               3. Unstable psychiatric illness including psychosis and untreated major depression&#xD;
&#xD;
         11. Any condition that the Investigator or primary physician feels may interfere with&#xD;
             participation in the study or may endanger the subject&#xD;
&#xD;
         12. Any condition that the surgeon feels may pose complications for the surgery&#xD;
&#xD;
         13. Known hypersensitivity to tacrolimus or methylprednisolone&#xD;
&#xD;
         14. Unable or unwilling to participate in physical and/or occupational therapy or return&#xD;
             to clinic for follow up examinations as scheduled&#xD;
&#xD;
         15. Inability to provide informed consent as determined by screening protocol.&#xD;
&#xD;
         16. Use of antiplatelet drugs less than 2 weeks before surgery&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>30 Years</minimum_age>
    <maximum_age>65 Years</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Xu Ruxiang, M.D</last_name>
    <role>Principal Investigator</role>
    <affiliation>BaYi Brain Hospital, Army General Hospital</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Ba Yi Brain Hospital</name>
      <address>
        <city>Beijing</city>
        <country>China</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Glass JD, Boulis NM, Johe K, Rutkove SB, Federici T, Polak M, Kelly C, Feldman EL. Lumbar intraspinal injection of neural stem cells in patients with amyotrophic lateral sclerosis: results of a phase I trial in 12 patients. Stem Cells. 2012 Jun;30(6):1144-51. doi: 10.1002/stem.1079.</citation>
    <PMID>22415942</PMID>
  </reference>
  <reference>
    <citation>Boulis NM, Federici T, Glass JD, Lunn JS, Sakowski SA, Feldman EL. Translational stem cell therapy for amyotrophic lateral sclerosis. Nat Rev Neurol. 2011 Dec 13;8(3):172-6. doi: 10.1038/nrneurol.2011.191.</citation>
    <PMID>22158518</PMID>
  </reference>
  <reference>
    <citation>Lunn JS, Sakowski SA, Hur J, Feldman EL. Stem cell technology for neurodegenerative diseases. Ann Neurol. 2011 Sep;70(3):353-61. doi: 10.1002/ana.22487.</citation>
    <PMID>21905078</PMID>
  </reference>
  <reference>
    <citation>Lunn JS, Sakowski SA, Federici T, Glass JD, Boulis NM, Feldman EL. Stem cell technology for the study and treatment of motor neuron diseases. Regen Med. 2011 Mar;6(2):201-13. doi: 10.2217/rme.11.6. Erratum In: Regen Med. 2011 Jul;6(4):536.</citation>
    <PMID>21391854</PMID>
  </reference>
  <verification_date>October 2017</verification_date>
  <study_first_submitted>September 22, 2017</study_first_submitted>
  <study_first_submitted_qc>September 25, 2017</study_first_submitted_qc>
  <study_first_posted type="Actual">September 28, 2017</study_first_posted>
  <last_update_submitted>October 3, 2017</last_update_submitted>
  <last_update_submitted_qc>October 3, 2017</last_update_submitted_qc>
  <last_update_posted type="Actual">October 5, 2017</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>chronic stroke</keyword>
  <keyword>neural stem cell</keyword>
  <keyword>transplant</keyword>
  <keyword>paralysis</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Stroke</mesh_term>
    <mesh_term>Ischemic Stroke</mesh_term>
    <mesh_term>Ischemia</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/NCT03296618
org study id: NS2012-1
nct id: NCT03296618
lead sponsor: 
has dmc: No
is fda regulated drug: No
is fda regulated device: No
The study is to determine the safety of human neural stem cell transplantation for the
      treatment of paralysis and related symptoms due to chronic motor stroke and to determine the
      maximum tolerated dose.
This is a Phase I study of human neural stem cell transplantation for the treatment of
      chronic motor stroke. This single-site, Phase I, open-label study may enroll up to 18
      patients across 5 cohorts of ascending doses of human neural stem cells to define maximal
      tolerated dose.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse Events
time frame: 24 months
measure: Clinical improvement using NIH Stroke Scale
time frame: 12 months
measure: Clinical improvement using Modified Rankin Scale
time frame: 12 months
measure: Clinical improvement using Fugl-Meyer Motor Score
time frame: 12 months
measure: Clinical Improvement using Mini-mental State Examination
time frame: 12 months
measure: MRI analysis of transplant site
time frame: 12 months
measure: PET analysis of transplant site
time frame: 12 months
arm group label: NSI-566 neural stem cell implantation
arm group type: Experimental
intervention type: Drug
intervention name: NSI-566
description: Dosing will consist of a one-time stereotactic, intracranial injection of a hNSC line, NSI-566, ranging from 1.2×107 cells to 8×107 cells, as tolerated.
arm group label: NSI-566 neural stem cell implantation
criteria: 
gender: All
minimum age: 30 Years
maximum age: 65 Years
healthy volunteers: No
last name: Xu Ruxiang, M.D
role: Principal Investigator
affiliation: BaYi Brain Hospital, Army General Hospital
facility: 
country: China
citation: Glass JD, Boulis NM, Johe K, Rutkove SB, Federici T, Polak M, Kelly C, Feldman EL. Lumbar intraspinal injection of neural stem cells in patients with amyotrophic lateral sclerosis: results of a phase I trial in 12 patients. Stem Cells. 2012 Jun;30(6):1144-51. doi: 10.1002/stem.1079.
PMID: 22415942
citation: Boulis NM, Federici T, Glass JD, Lunn JS, Sakowski SA, Feldman EL. Translational stem cell therapy for amyotrophic lateral sclerosis. Nat Rev Neurol. 2011 Dec 13;8(3):172-6. doi: 10.1038/nrneurol.2011.191.
PMID: 22158518
citation: Lunn JS, Sakowski SA, Hur J, Feldman EL. Stem cell technology for neurodegenerative diseases. Ann Neurol. 2011 Sep;70(3):353-61. doi: 10.1002/ana.22487.
PMID: 21905078
citation: Lunn JS, Sakowski SA, Federici T, Glass JD, Boulis NM, Feldman EL. Stem cell technology for the study and treatment of motor neuron diseases. Regen Med. 2011 Mar;6(2):201-13. doi: 10.2217/rme.11.6. Erratum In: Regen Med. 2011 Jul;6(4):536.
PMID: 21391854
responsible party type: Sponsor
mesh term: Stroke
mesh term: Ischemic Stroke
mesh term: Ischemia