<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/NCT03774537</url>
  </required_header>
  <id_info>
    <org_study_id>XiaYQ</org_study_id>
    <nct_id>NCT03774537</nct_id>
  </id_info>
  <brief_title>Human Mesenchymal Stem Cells For Infants At High Risk For Bronchopulmonary Dysplasia</brief_title>
  <official_title>Intravenous Human Umbilical-Cord-Derived Mesenchymal Stem Cells For Premature Infants Ａt High Risk For Bronchopulmonary</official_title>
  <sponsors>
    <lead_sponsor>
      <agency>Children's Hospital of Chongqing Medical University</agency>
      <agency_class>Other</agency_class>
    </lead_sponsor>
  </sponsors>
  <source>Children's Hospital of Chongqing Medical University</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>
      This study is an open-label, single-center, dose escalation study to evaluate of safety and&#xD;
      efficacy of human umbilical cord -derived mesenchymal stem cells (hUC-MSCs) in premature&#xD;
      infants at high risk for Bronchopulmonary Dysplasia（BPD）&#xD;
    </textblock>
  </brief_summary>
  <detailed_description>
    <textblock>
      BPD is a chronic lung disease that occur in premature infants receiving prolonged oxygen&#xD;
      pulmonary and ventilator therapy. It remains a main complication of extreme prematurity and&#xD;
      currently lacks efficient treatment.The mortality rate of one year after birth is still high&#xD;
      and the quality of life is not optimistic.&#xD;
&#xD;
      hUC-MSCs are widely used in clinic due to their low immunogenicity and convenient to get.&#xD;
      Many animal study had shown that hUC-MSCs had therapeutic effects on a variety of animal&#xD;
      models of lung disease.Furthermore,there are a large number of clinical trials of MSCs&#xD;
      applied to various system diseases and the safety was verified.So, the main purpose of this&#xD;
      study is to evaluate the safety and efficacy of hUC-MSCs in participants at high risk for BPD&#xD;
    </textblock>
  </detailed_description>
  <overall_status>Unknown status</overall_status>
  <last_known_status>Recruiting</last_known_status>
  <start_date type="Actual">March 1, 2019</start_date>
  <completion_date type="Anticipated">December 31, 2021</completion_date>
  <primary_completion_date type="Anticipated">December 1, 2020</primary_completion_date>
  <phase>Phase 1/Phase 2</phase>
  <study_type>Interventional</study_type>
  <has_expanded_access>No</has_expanded_access>
  <study_design_info>
    <allocation>Non-Randomized</allocation>
    <intervention_model>Parallel Assignment</intervention_model>
    <primary_purpose>Treatment</primary_purpose>
    <masking>None (Open Label)</masking>
  </study_design_info>
  <primary_outcome>
    <measure>Number of participants with adverse reactions related to infusion after treatment</measure>
    <time_frame>24 hours after administration</time_frame>
    <description>To evaluate the safety of hUC-MSCs for BPD.</description>
  </primary_outcome>
  <secondary_outcome>
    <measure>The incidence and severity of BPD defined by the National Institutes of Child Health and Human Development (NICHD) workshop.</measure>
    <time_frame>at the corrected gestational age of 36 weeks</time_frame>
    <description>To evaluate the efficacy of hUC-MSCs to prevent preterm infants at high risk of BPD from developing BPD</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of high-resolution chest CT in participants</measure>
    <time_frame>within 2 years after administration</time_frame>
    <description>To evaluate the safety and efficacy of human umbilical cord -derived mesenchymal stem cells for BPDmesenchymal stem cells for BPD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of temperature in participants</measure>
    <time_frame>3 days after administration</time_frame>
    <description>To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD.mesenchymal stem cells for BPD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of blood pressure in participants</measure>
    <time_frame>3 days after administration</time_frame>
    <description>To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD. Blood pressure is measured by electronic sphygmomanometer.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of respiratory rate in participants</measure>
    <time_frame>3 days after administration</time_frame>
    <description>To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD.</description>
  </secondary_outcome>
  <secondary_outcome>
    <measure>Changes of oxygen saturation in participants</measure>
    <time_frame>3 days after administration</time_frame>
    <description>To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD.</description>
  </secondary_outcome>
  <number_of_arms>2</number_of_arms>
  <enrollment type="Anticipated">20</enrollment>
  <condition>Bronchopulmonary Dysplasia</condition>
  <arm_group>
    <arm_group_label>Transplantation of hUC-MSCs</arm_group_label>
    <arm_group_type>Experimental</arm_group_type>
    <description>Preterm infants at high risk for BPD will receive transplantation of hUC-MSCs.</description>
  </arm_group>
  <arm_group>
    <arm_group_label>No transplantation of hUC-MSCs</arm_group_label>
    <arm_group_type>Other</arm_group_type>
    <description>Preterm infants at high risk for BPD will not receive transplantation of hUC-MSCs</description>
  </arm_group>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>Transplantation of hUC-MSCs</intervention_name>
    <description>Preterm infants at high risk for BPD will receive transplantation of hUC-MSCs through intravenous infusion. Dose A - 1 million cells per kg; Dose B - 5 million cells per kg</description>
    <arm_group_label>Transplantation of hUC-MSCs</arm_group_label>
    <other_name>Intravenous infusion of hUC-MSCs</other_name>
  </intervention>
  <intervention>
    <intervention_type>Drug</intervention_type>
    <intervention_name>No transplantation of hUC-MSCs</intervention_name>
    <description>Preterm infants at high risk for BPD will not receive transplantation of hUC-MSCs</description>
    <arm_group_label>No transplantation of hUC-MSCs</arm_group_label>
    <other_name>No intravenous infusion of hUC-MSCs</other_name>
  </intervention>
  <eligibility>
    <criteria>
      <textblock>
        Inclusion Criteria:&#xD;
&#xD;
          1. An infant whose postnatal age is 3 to 14 days, inclusive (for treatment between 5 and&#xD;
             14 days after birth)&#xD;
&#xD;
          2. Gestational age is between 23 and 28 weeks (23 weeks ≤ gestational age (GA) &lt; 28&#xD;
             weeks)&#xD;
&#xD;
          3. Birth weight is between 500g and 1000g, inclusive&#xD;
&#xD;
          4. Being intubated and receiving mechanical ventilation within 5-14 days after birth,&#xD;
             with a fraction of inspired oxygen (FiO2) of 0.25 or greater at Screening&#xD;
&#xD;
          5. Written consent form signed by a legal representative or a parent.&#xD;
&#xD;
        Exclusion Criteria:&#xD;
&#xD;
          1. Although mechanical ventilation or oxygen is required in participants, there are no&#xD;
             signs of dyspnea or BPD-related changes in lung imaging, such as central apnea or&#xD;
             diaphragm paralysis.&#xD;
&#xD;
          2. The participants who have complex congenital heart disease.&#xD;
&#xD;
          3. The participants who have severe pulmonary hypertension(cardiac ultrasound confirmed)&#xD;
             at the time of assessment.&#xD;
&#xD;
          4. The participants who have severe respiratory tract malformation: pierre-robin&#xD;
             syndrome, tracheobronchomalacia, vascular ring syndrome, congenital tracheal stenosis,&#xD;
             tracheo-esophageal fistula, pulmonary emphysema, pulmonary sequestration, congenital&#xD;
             pulmonary dysplasia, congenital pulmonary cyst, congenital spasm, etc.&#xD;
&#xD;
          5. The participants who have severe chromosome anomalies :Edward syndrome, Patau&#xD;
             syndrome, Down syndrome, etc) or severe congenital malformation (Hydrocephalus,&#xD;
             Encephalocele, etc).&#xD;
&#xD;
          6. The participants who have severe congenital infection(Herpes, Toxoplasmosis, Rubella,&#xD;
             Syphilis, AIDS, etc).&#xD;
&#xD;
          7. The participants who have severe sepsis or shock.&#xD;
&#xD;
          8. The participants who is going to have surgery 72 hours before/after this study drug&#xD;
             administration.&#xD;
&#xD;
          9. The participants who have surfactant administration within 24 hours before this study&#xD;
             drug administration.&#xD;
&#xD;
         10. The participants who have severe intracranial hemorrhage ≥ grade 3 or 4.&#xD;
&#xD;
         11. The participants who have active pulmonary hemorrhage or active air leak syndrome at&#xD;
             the time of assessment.&#xD;
&#xD;
         12. The participants who have the history of other clinical studies as a participant.&#xD;
&#xD;
         13. The participants who is considered inappropriate by the investigators.&#xD;
      </textblock>
    </criteria>
    <gender>All</gender>
    <minimum_age>4 Days</minimum_age>
    <maximum_age>14 Days</maximum_age>
    <healthy_volunteers>No</healthy_volunteers>
  </eligibility>
  <overall_official>
    <last_name>Zhou Fu</last_name>
    <role>Study Chair</role>
    <affiliation>Children's Hospital of Chongqing Medical University</affiliation>
  </overall_official>
  <overall_contact>
    <last_name>Yunqiu xia</last_name>
    <phone>13637719980</phone>
    <email>sunny_199001@foxmail.com</email>
  </overall_contact>
  <overall_contact_backup>
    <last_name>Lin Zou</last_name>
    <phone>18623121280</phone>
  </overall_contact_backup>
  <location>
    <facility>
      <name>Children's Hospital of Chongqing Medical University</name>
      <address>
        <city>Chongqing</city>
        <state>Chongqing</state>
        <country>China</country>
      </address>
    </facility>
    <status>Recruiting</status>
    <contact>
      <last_name>Yunqiu Xia</last_name>
      <phone>13637719980</phone>
    </contact>
  </location>
  <location_countries>
    <country>China</country>
  </location_countries>
  <reference>
    <citation>Chang YS, Ahn SY, Yoo HS, Sung SI, Choi SJ, Oh WI, Park WS. Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. J Pediatr. 2014 May;164(5):966-972.e6. doi: 10.1016/j.jpeds.2013.12.011. Epub 2014 Feb 6.</citation>
    <PMID>24508444</PMID>
  </reference>
  <reference>
    <citation>Hayes D Jr, Meadows JT Jr, Murphy BS, Feola DJ, Shook LA, Ballard HO. Pulmonary function outcomes in bronchopulmonary dysplasia through childhood and into adulthood: implications for primary care. Prim Care Respir J. 2011 Jun;20(2):128-33. doi: 10.4104/pcrj.2011.00002.</citation>
    <PMID>21336467</PMID>
  </reference>
  <reference>
    <citation>Ahn SY, Chang YS, Kim JH, Sung SI, Park WS. Two-Year Follow-Up Outcomes of Premature Infants Enrolled in the Phase I Trial of Mesenchymal Stem Cells Transplantation for Bronchopulmonary Dysplasia. J Pediatr. 2017 Jun;185:49-54.e2. doi: 10.1016/j.jpeds.2017.02.061. Epub 2017 Mar 21.</citation>
    <PMID>28341525</PMID>
  </reference>
  <reference>
    <citation>Wilson JG, Liu KD, Zhuo H, Caballero L, McMillan M, Fang X, Cosgrove K, Vojnik R, Calfee CS, Lee JW, Rogers AJ, Levitt J, Wiener-Kronish J, Bajwa EK, Leavitt A, McKenna D, Thompson BT, Matthay MA. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respir Med. 2015 Jan;3(1):24-32. doi: 10.1016/S2213-2600(14)70291-7. Epub 2014 Dec 17.</citation>
    <PMID>25529339</PMID>
  </reference>
  <reference>
    <citation>Laube M, Stolzing A, Thome UH, Fabian C. Therapeutic potential of mesenchymal stem cells for pulmonary complications associated with preterm birth. Int J Biochem Cell Biol. 2016 May;74:18-32. doi: 10.1016/j.biocel.2016.02.023. Epub 2016 Feb 27.</citation>
    <PMID>26928452</PMID>
  </reference>
  <reference>
    <citation>Pierro M, Ionescu L, Montemurro T, Vadivel A, Weissmann G, Oudit G, Emery D, Bodiga S, Eaton F, Peault B, Mosca F, Lazzari L, Thebaud B. Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia. Thorax. 2013 May;68(5):475-84. doi: 10.1136/thoraxjnl-2012-202323. Epub 2012 Dec 4.</citation>
    <PMID>23212278</PMID>
  </reference>
  <reference>
    <citation>Hansmann G, Fernandez-Gonzalez A, Aslam M, Vitali SH, Martin T, Mitsialis SA, Kourembanas S. Mesenchymal stem cell-mediated reversal of bronchopulmonary dysplasia and associated pulmonary hypertension. Pulm Circ. 2012 Apr-Jun;2(2):170-81. doi: 10.4103/2045-8932.97603.</citation>
    <PMID>22837858</PMID>
  </reference>
  <reference>
    <citation>Yeh TF, Chen CM, Wu SY, Husan Z, Li TC, Hsieh WS, Tsai CH, Lin HC. Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia. Am J Respir Crit Care Med. 2016 Jan 1;193(1):86-95. doi: 10.1164/rccm.201505-0861OC.</citation>
    <PMID>26351971</PMID>
  </reference>
  <verification_date>March 2019</verification_date>
  <study_first_submitted>December 12, 2018</study_first_submitted>
  <study_first_submitted_qc>December 12, 2018</study_first_submitted_qc>
  <study_first_posted type="Actual">December 13, 2018</study_first_posted>
  <last_update_submitted>March 5, 2019</last_update_submitted>
  <last_update_submitted_qc>March 5, 2019</last_update_submitted_qc>
  <last_update_posted type="Actual">March 6, 2019</last_update_posted>
  <responsible_party>
    <responsible_party_type>Principal Investigator</responsible_party_type>
    <investigator_affiliation>Children's Hospital of Chongqing Medical University</investigator_affiliation>
    <investigator_full_name>Xia Yunqiu</investigator_full_name>
    <investigator_title>Director</investigator_title>
  </responsible_party>
  <keyword>high risk； Bronchopulmonary Dysplasia；hUC-MSCs</keyword>
  <condition_browse>
    <!-- CAUTION:  The following MeSH terms are assigned with an imperfect algorithm            -->
    <mesh_term>Bronchopulmonary Dysplasia</mesh_term>
  </condition_browse>
  <patient_data>
    <sharing_ipd>No</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/NCT03774537
org study id: XiaYQ
nct id: NCT03774537
lead sponsor: 
has dmc: Yes
is fda regulated drug: No
is fda regulated device: No
This study is an open-label, single-center, dose escalation study to evaluate of safety and
      efficacy of human umbilical cord -derived mesenchymal stem cells (hUC-MSCs) in premature
      infants at high risk for Bronchopulmonary Dysplasia（BPD）
BPD is a chronic lung disease that occur in premature infants receiving prolonged oxygen
      pulmonary and ventilator therapy. It remains a main complication of extreme prematurity and
      currently lacks efficient treatment.The mortality rate of one year after birth is still high
      and the quality of life is not optimistic.

      hUC-MSCs are widely used in clinic due to their low immunogenicity and convenient to get.
      Many animal study had shown that hUC-MSCs had therapeutic effects on a variety of animal
      models of lung disease.Furthermore,there are a large number of clinical trials of MSCs
      applied to various system diseases and the safety was verified.So, the main purpose of this
      study is to evaluate the safety and efficacy of hUC-MSCs in participants at high risk for BPD
allocation: Non-Randomized
intervention model: Parallel Assignment
primary purpose: Treatment
masking: None (Open Label)
measure: Number of participants with adverse reactions related to infusion after treatment
time frame: 24 hours after administration
description: To evaluate the safety of hUC-MSCs for BPD.
measure: The incidence and severity of BPD defined by the National Institutes of Child Health and Human Development (NICHD) workshop.
time frame: at the corrected gestational age of 36 weeks
description: To evaluate the efficacy of hUC-MSCs to prevent preterm infants at high risk of BPD from developing BPD
measure: Changes of high-resolution chest CT in participants
time frame: within 2 years after administration
description: To evaluate the safety and efficacy of human umbilical cord -derived mesenchymal stem cells for BPDmesenchymal stem cells for BPD.
measure: Changes of temperature in participants
time frame: 3 days after administration
description: To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD.mesenchymal stem cells for BPD.
measure: Changes of blood pressure in participants
time frame: 3 days after administration
description: To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD. Blood pressure is measured by electronic sphygmomanometer.
measure: Changes of respiratory rate in participants
time frame: 3 days after administration
description: To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD.
measure: Changes of oxygen saturation in participants
time frame: 3 days after administration
description: To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD.
arm group label: Transplantation of hUC-MSCs
arm group type: Experimental
description: Preterm infants at high risk for BPD will receive transplantation of hUC-MSCs.
arm group label: No transplantation of hUC-MSCs
arm group type: Other
description: Preterm infants at high risk for BPD will not receive transplantation of hUC-MSCs
intervention type: Drug
intervention name: Transplantation of hUC-MSCs
description: Preterm infants at high risk for BPD will receive transplantation of hUC-MSCs through intravenous infusion. Dose A - 1 million cells per kg; Dose B - 5 million cells per kg
arm group label: Transplantation of hUC-MSCs
other name: Intravenous infusion of hUC-MSCs
intervention type: Drug
intervention name: No transplantation of hUC-MSCs
description: Preterm infants at high risk for BPD will not receive transplantation of hUC-MSCs
arm group label: No transplantation of hUC-MSCs
other name: No intravenous infusion of hUC-MSCs
criteria: 
gender: All
minimum age: 4 Days
maximum age: 14 Days
healthy volunteers: No
last name: Zhou Fu
role: Study Chair
affiliation: Children's Hospital of Chongqing Medical University
last name: Yunqiu xia
phone: 13637719980
email: sunny_199001@foxmail.com
last name: Lin Zou
phone: 18623121280
facility: 
status: Recruiting
contact: 
country: China
citation: Chang YS, Ahn SY, Yoo HS, Sung SI, Choi SJ, Oh WI, Park WS. Mesenchymal stem cells for bronchopulmonary dysplasia: phase 1 dose-escalation clinical trial. J Pediatr. 2014 May;164(5):966-972.e6. doi: 10.1016/j.jpeds.2013.12.011. Epub 2014 Feb 6.
PMID: 24508444
citation: Hayes D Jr, Meadows JT Jr, Murphy BS, Feola DJ, Shook LA, Ballard HO. Pulmonary function outcomes in bronchopulmonary dysplasia through childhood and into adulthood: implications for primary care. Prim Care Respir J. 2011 Jun;20(2):128-33. doi: 10.4104/pcrj.2011.00002.
PMID: 21336467
citation: Ahn SY, Chang YS, Kim JH, Sung SI, Park WS. Two-Year Follow-Up Outcomes of Premature Infants Enrolled in the Phase I Trial of Mesenchymal Stem Cells Transplantation for Bronchopulmonary Dysplasia. J Pediatr. 2017 Jun;185:49-54.e2. doi: 10.1016/j.jpeds.2017.02.061. Epub 2017 Mar 21.
PMID: 28341525
citation: Wilson JG, Liu KD, Zhuo H, Caballero L, McMillan M, Fang X, Cosgrove K, Vojnik R, Calfee CS, Lee JW, Rogers AJ, Levitt J, Wiener-Kronish J, Bajwa EK, Leavitt A, McKenna D, Thompson BT, Matthay MA. Mesenchymal stem (stromal) cells for treatment of ARDS: a phase 1 clinical trial. Lancet Respir Med. 2015 Jan;3(1):24-32. doi: 10.1016/S2213-2600(14)70291-7. Epub 2014 Dec 17.
PMID: 25529339
citation: Laube M, Stolzing A, Thome UH, Fabian C. Therapeutic potential of mesenchymal stem cells for pulmonary complications associated with preterm birth. Int J Biochem Cell Biol. 2016 May;74:18-32. doi: 10.1016/j.biocel.2016.02.023. Epub 2016 Feb 27.
PMID: 26928452
citation: Pierro M, Ionescu L, Montemurro T, Vadivel A, Weissmann G, Oudit G, Emery D, Bodiga S, Eaton F, Peault B, Mosca F, Lazzari L, Thebaud B. Short-term, long-term and paracrine effect of human umbilical cord-derived stem cells in lung injury prevention and repair in experimental bronchopulmonary dysplasia. Thorax. 2013 May;68(5):475-84. doi: 10.1136/thoraxjnl-2012-202323. Epub 2012 Dec 4.
PMID: 23212278
citation: Hansmann G, Fernandez-Gonzalez A, Aslam M, Vitali SH, Martin T, Mitsialis SA, Kourembanas S. Mesenchymal stem cell-mediated reversal of bronchopulmonary dysplasia and associated pulmonary hypertension. Pulm Circ. 2012 Apr-Jun;2(2):170-81. doi: 10.4103/2045-8932.97603.
PMID: 22837858
citation: Yeh TF, Chen CM, Wu SY, Husan Z, Li TC, Hsieh WS, Tsai CH, Lin HC. Intratracheal Administration of Budesonide/Surfactant to Prevent Bronchopulmonary Dysplasia. Am J Respir Crit Care Med. 2016 Jan 1;193(1):86-95. doi: 10.1164/rccm.201505-0861OC.
PMID: 26351971
responsible party type: Principal Investigator
investigator affiliation: Children's Hospital of Chongqing Medical University
investigator full name: Xia Yunqiu
investigator title: Director
mesh term: Bronchopulmonary Dysplasia
sharing ipd: No