<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/NCT02256618</url>
  </required_header>
  <id_info>
    <org_study_id>UMIN000014903</org_study_id>
    <nct_id>NCT02256618</nct_id>
  </id_info>
  <brief_title>Autologous Cord Blood Cell Therapy for Neonatal Encephalopathy</brief_title>
  <official_title>A Pilot Feasibility and Safety Study of Autologous Umbilical Cord Blood Cell Therapy in Infants With Neonatal Encephalopathy</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Neonatal Encephalopathy Consortium, Japan</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
    <collaborator>
      <agency>Osaka City University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Yodogawa Christian Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Kurashiki Central Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Nagoya University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Osaka City General Hospital</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Saitama Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Cerebral and Cardiovascular Center</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>National Center for Child Health and Development, Japan</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tokyo University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
    <collaborator>
      <agency>Tokyo Women's Medical University</agency>
      <agency_class>Other</agency_class>
    </collaborator>
  </sponsors>
  <source>Neonatal Encephalopathy Consortium, Japan</source>
  <oversight_info>
    <has_dmc>Yes</has_dmc>
  </oversight_info>
  <brief_summary>
    <textblock>
      This is a pilot study to test feasibility and safety of intravenous infusion of autologous&#xD;
      umbilical cord blood cells in the first 72 hours after birth if a neonate is born with signs&#xD;
      of encephalopathy.&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      This is a multicenter pilot study to evaluate the feasibility and safety of intravenous&#xD;
      infusions of autologous (the patient's own) umbilical cord blood cells in term gestation&#xD;
      newborns with neonatal encephalopathy (hypoxic-ischemic encephalopathy). If a neonate is born&#xD;
      with signs of moderate to severe encephalopathy and cooled for the encephalopathy, the&#xD;
      neonate can receive their own non-cryopreserved volume- and red blood cell-reduced cord blood&#xD;
      cells. The cord blood cells are divided into 3 doses and infused at 12-24, 36-48, and 60-72&#xD;
      hours after the birth. Infants will be followed for safety and neurodevelopmental outcome up&#xD;
      to 18 months.&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Completed</overall_status>
  <start_date>August 2014</start_date>
  <completion_date type="Actual">July 2019</completion_date>
  <primary_completion_date type="Actual">October 2017</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 event rates</measure>
    <time_frame>first 30 postnatal days</time_frame>
    <description>Adverse event rates (combined rate of death, continuous respiratory support, and continuous use of vasopressor) will be compared between the cell recipients and historical controls at 30 days of age.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>Efficacy</measure>
    <time_frame>18 months</time_frame>
    <description>Neuroimaging at 12 months of age and neurodevelopmental function at 18 months of age will be compared between the cell recipients and historical controls.</description>
  </secondary_outcome>
  <number_of_arms>1</number_of_arms>
  <enrollment type="Actual">6</enrollment>
  <condition>Neonatal Encephalopathy</condition>
  <condition>Hypoxic-ischemic Encephalopathy</condition>
  <arm_group>
    <arm_group_label>Cell therapy</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Infants who are born at the study sites, have moderate to severe encephalopathy, and have cord blood available for infusion</description>
  </arm_group>
  <intervention>
    <intervention_type>Other</intervention_type>
    <intervention_name>Autologous umbilical cord blood cells</intervention_name>
    <description>Autologous non-cryopreserved volume- and red blood cell-reduced cord blood cells will be intravenously infused</description>
    <arm_group_label>Cell therapy</arm_group_label>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
        Infants are eligible if they meet all the following inclusion criteria except 4.&#xD;
&#xD;
          1. ≥36 weeks gestation&#xD;
&#xD;
          2. Either a 10-minute Apgar score ≤5, continued need for resuscitation for at least 10&#xD;
             minutes, or severe acidosis, defined as pH &lt;7.0 or base deficit ≥16 mmol/L in a sample&#xD;
             of umbilical cord blood or any blood during the first hour after birth&#xD;
&#xD;
          3. Moderate to severe encephalopathy (Sarnat II to III)&#xD;
&#xD;
          4. A moderately or severely abnormal background amplitude-integrated EEG (aEEG) voltage,&#xD;
             or seizures identified by aEEG, if monitored&#xD;
&#xD;
          5. Up to 24 hours of age&#xD;
&#xD;
          6. Autologous umbilical cord blood available to infuse within 3 days after birth&#xD;
&#xD;
          7. A person with parental authority must have consented for the study.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Known major congenital anomalies, such as chromosomal anomalies, heart diseases&#xD;
&#xD;
          2. Major intracranial hemorrhage identified by brain ultrasonography or computed&#xD;
             tomography&#xD;
&#xD;
          3. Severe growth restriction, with birth-weight less than 1800 g&#xD;
&#xD;
          4. Severe infectious disease, such as sepsis&#xD;
&#xD;
          5. Hyperkalemia&#xD;
&#xD;
          6. Outborn infants (Infants born at hospitals other than the study sites)&#xD;
&#xD;
          7. Volume of collected cord blood &lt;40 ml&#xD;
&#xD;
          8. Infants judged critically ill and unlikely to benefit from neonatal intensive care by&#xD;
             the attending neonatologist&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>N/A</minimum_age>
    <maximum_age>24 Hours</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Haruo Shintaku, MD, PhD</last_name>
    <role>Study Director</role>
    <affiliation>Osaka City University</affiliation>
  </overall_official>
  <location>
    <facility>
      <name>Nagoya University Hospital</name>
      <address>
        <city>Nagoya</city>
        <state>Aichi</state>
        <zip>466-8560</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Kurashiki Central Hospital</name>
      <address>
        <city>Kurashiki</city>
        <state>Okayama</state>
        <zip>710-8602</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Saitama Medical University</name>
      <address>
        <city>Kawagoe</city>
        <state>Saitama</state>
        <zip>350-0495</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Yodogawa Christian Hospital</name>
      <address>
        <city>Osaka</city>
        <zip>533-0032</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osaka City General Hospital</name>
      <address>
        <city>Osaka</city>
        <zip>534-0021</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location>
    <facility>
      <name>Osaka City University</name>
      <address>
        <city>Osaka</city>
        <zip>545-8585</zip>
        <country>Japan</country>
      </address>
    </facility>
  </location>
  <location_countries>
    <country>Japan</country>
  </location_countries>
  <reference>
    <citation>Tsuji M, Taguchi A, Ohshima M, Kasahara Y, Sato Y, Tsuda H, Otani K, Yamahara K, Ihara M, Harada-Shiba M, Ikeda T, Matsuyama T. Effects of intravenous administration of umbilical cord blood CD34(+) cells in a mouse model of neonatal stroke. Neuroscience. 2014 Mar 28;263:148-58. doi: 10.1016/j.neuroscience.2014.01.018. Epub 2014 Jan 18.</citation>
    <PMID>24444827</PMID>
  </reference>
  <reference>
    <citation>Ohshima M, Taguchi A, Tsuda H, Sato Y, Yamahara K, Harada-Shiba M, Miyazato M, Ikeda T, Iida H, Tsuji M. Intraperitoneal and intravenous deliveries are not comparable in terms of drug efficacy and cell distribution in neonatal mice with hypoxia-ischemia. Brain Dev. 2015 Apr;37(4):376-86. doi: 10.1016/j.braindev.2014.06.010. Epub 2014 Jul 14.</citation>
    <PMID>25034178</PMID>
  </reference>
  <reference>
    <citation>Taguchi A, Soma T, Tanaka H, Kanda T, Nishimura H, Yoshikawa H, Tsukamoto Y, Iso H, Fujimori Y, Stern DM, Naritomi H, Matsuyama T. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest. 2004 Aug;114(3):330-8. doi: 10.1172/JCI20622.</citation>
    <PMID>15286799</PMID>
  </reference>
  <verification_date>October 2019</verification_date>
  <study_first_submitted>October 1, 2014</study_first_submitted>
  <study_first_submitted_qc>October 1, 2014</study_first_submitted_qc>
  <study_first_posted type="Estimate">October 3, 2014</study_first_posted>
  <last_update_submitted>October 28, 2019</last_update_submitted>
  <last_update_submitted_qc>October 28, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">October 29, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Sponsor</responsible_party_type>
  </responsible_party>
  <keyword>neonatal encephalopathy</keyword>
  <keyword>hypoxic-ischemic encephalopathy</keyword>
  <keyword>newborn infants</keyword>
  <keyword>neonates</keyword>
  <keyword>umbilical cord blood cells</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Brain Diseases</mesh_term>
    <mesh_term>Brain Ischemia</mesh_term>
    <mesh_term>Hypoxia-Ischemia, Brain</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/NCT02256618
org study id: UMIN000014903
nct id: NCT02256618
lead sponsor: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
collaborator: 
has dmc: Yes
This is a pilot study to test feasibility and safety of intravenous infusion of autologous
      umbilical cord blood cells in the first 72 hours after birth if a neonate is born with signs
      of encephalopathy.
This is a multicenter pilot study to evaluate the feasibility and safety of intravenous
      infusions of autologous (the patient's own) umbilical cord blood cells in term gestation
      newborns with neonatal encephalopathy (hypoxic-ischemic encephalopathy). If a neonate is born
      with signs of moderate to severe encephalopathy and cooled for the encephalopathy, the
      neonate can receive their own non-cryopreserved volume- and red blood cell-reduced cord blood
      cells. The cord blood cells are divided into 3 doses and infused at 12-24, 36-48, and 60-72
      hours after the birth. Infants will be followed for safety and neurodevelopmental outcome up
      to 18 months.
allocation: N/A
intervention model: Single Group Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Adverse event rates
time frame: first 30 postnatal days
description: Adverse event rates (combined rate of death, continuous respiratory support, and continuous use of vasopressor) will be compared between the cell recipients and historical controls at 30 days of age.
measure: Efficacy
time frame: 18 months
description: Neuroimaging at 12 months of age and neurodevelopmental function at 18 months of age will be compared between the cell recipients and historical controls.
arm group label: Cell therapy
arm group type: Experimental
description: Infants who are born at the study sites, have moderate to severe encephalopathy, and have cord blood available for infusion
intervention type: Other
intervention name: Autologous umbilical cord blood cells
description: Autologous non-cryopreserved volume- and red blood cell-reduced cord blood cells will be intravenously infused
arm group label: Cell therapy
criteria: 
gender: All
minimum age: N/A
maximum age: 24 Hours
healthy volunteers: No
last name: Haruo Shintaku, MD, PhD
role: Study Director
affiliation: Osaka City University
facility: 
facility: 
facility: 
facility: 
facility: 
facility: 
country: Japan
citation: Tsuji M, Taguchi A, Ohshima M, Kasahara Y, Sato Y, Tsuda H, Otani K, Yamahara K, Ihara M, Harada-Shiba M, Ikeda T, Matsuyama T. Effects of intravenous administration of umbilical cord blood CD34(+) cells in a mouse model of neonatal stroke. Neuroscience. 2014 Mar 28;263:148-58. doi: 10.1016/j.neuroscience.2014.01.018. Epub 2014 Jan 18.
PMID: 24444827
citation: Ohshima M, Taguchi A, Tsuda H, Sato Y, Yamahara K, Harada-Shiba M, Miyazato M, Ikeda T, Iida H, Tsuji M. Intraperitoneal and intravenous deliveries are not comparable in terms of drug efficacy and cell distribution in neonatal mice with hypoxia-ischemia. Brain Dev. 2015 Apr;37(4):376-86. doi: 10.1016/j.braindev.2014.06.010. Epub 2014 Jul 14.
PMID: 25034178
citation: Taguchi A, Soma T, Tanaka H, Kanda T, Nishimura H, Yoshikawa H, Tsukamoto Y, Iso H, Fujimori Y, Stern DM, Naritomi H, Matsuyama T. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest. 2004 Aug;114(3):330-8. doi: 10.1172/JCI20622.
PMID: 15286799
responsible party type: Sponsor
mesh term: Brain Diseases
mesh term: Brain Ischemia
mesh term: Hypoxia-Ischemia, Brain