Human Mesenchymal Stem Cells For Infants At High Risk For Bronchopulmonary Dysplasia

Study Overview
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Brief Summary
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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）

Detailed Description
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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

Official Title
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Intravenous Human Umbilical-Cord-Derived Mesenchymal Stem Cells For Premature Infants Ａt High Risk For Bronchopulmonary

Conditions
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Bronchopulmonary Dysplasia

Intervention / Treatment
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* Drug: Transplantation of hUC-MSCs
* Drug: No transplantation of hUC-MSCs


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: An infant whose postnatal age is 3 to 14 days, inclusive (for treatment between 5 and 14 days after birth) Gestational age is between 23 and 28 weeks (23 weeks ≤ gestational age (GA) < 28 weeks) Birth weight is between 500g and 1000g, inclusive Being intubated and receiving mechanical ventilation within 5-14 days after birth, with a fraction of inspired oxygen (FiO2) of 0.25 or greater at Screening Written consent form signed by a legal representative or a parent. Exclusion Criteria: Although mechanical ventilation or oxygen is required in participants, there are no signs of dyspnea or BPD-related changes in lung imaging, such as central apnea or diaphragm paralysis. The participants who have complex congenital heart disease. The participants who have severe pulmonary hypertension(cardiac ultrasound confirmed) at the time of assessment. The participants who have severe respiratory tract malformation: pierre-robin syndrome, tracheobronchomalacia, vascular ring syndrome, congenital tracheal stenosis, tracheo-esophageal fistula, pulmonary emphysema, pulmonary sequestration, congenital pulmonary dysplasia, congenital pulmonary cyst, congenital spasm, etc. The participants who have severe chromosome anomalies :Edward syndrome, Patau syndrome, Down syndrome, etc) or severe congenital malformation (Hydrocephalus, Encephalocele, etc). The participants who have severe congenital infection(Herpes, Toxoplasmosis, Rubella, Syphilis, AIDS, etc). The participants who have severe sepsis or shock. The participants who is going to have surgery 72 hours before/after this study drug administration. The participants who have surfactant administration within 24 hours before this study drug administration. The participants who have severe intracranial hemorrhage ≥ grade 3 or 4. The participants who have active pulmonary hemorrhage or active air leak syndrome at the time of assessment. The participants who have the history of other clinical studies as a participant. The participants who is considered inappropriate by the investigators.

Ages Eligible for Study
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Minimum Age: 4 Days
Maximum Age: 14 Days

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Transplantation of hUC-MSCs<br>Preterm infants at high risk for BPD will receive transplantation of hUC-MSCs. | Drug: Transplantation of hUC-MSCs<br>* 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<br>* Other names: Intravenous infusion of hUC-MSCs;|
| Other: No transplantation of hUC-MSCs<br>Preterm infants at high risk for BPD will not receive transplantation of hUC-MSCs | Drug: No transplantation of hUC-MSCs<br>* Preterm infants at high risk for BPD will not receive transplantation of hUC-MSCs<br>* Other names: No intravenous infusion of hUC-MSCs;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of participants with adverse reactions related to infusion after treatment | To evaluate the safety of hUC-MSCs for BPD. | 24 hours after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The incidence and severity of BPD defined by the National Institutes of Child Health and Human Development (NICHD) workshop. | To evaluate the efficacy of hUC-MSCs to prevent preterm infants at high risk of BPD from developing BPD | at the corrected gestational age of 36 weeks | 
| Changes of high-resolution chest CT in participants | To evaluate the safety and efficacy of human umbilical cord -derived mesenchymal stem cells for BPDmesenchymal stem cells for BPD. | within 2 years after administration | 
| Changes of temperature in participants | To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD.mesenchymal stem cells for BPD. | 3 days after administration | 
| Changes of blood pressure in participants | To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD. Blood pressure is measured by electronic sphygmomanometer. | 3 days after administration | 
| Changes of respiratory rate in participants | To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD. | 3 days after administration | 
| Changes of oxygen saturation in participants | To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD. | 3 days after administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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high risk； Bronchopulmonary Dysplasia；hUC-MSCs