Human Mesenchymal Stem Cells 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 for moderate and severe 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 with moderate and severe BPD.

Official Title
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Intravenous Human Umbilical-Cord-Derived Mesenchymal Stem Cells For Moderate and Severe Bronchopulmonary Dysplasia in Premature Infants

Conditions
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Bronchopulmonary Dysplasia

Intervention / Treatment
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* Drug: Transplantation of mesenchymal stem cell
* Drug: No transplantation of mesenchymal stem cell


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: The participants meet the diagnostic criteria for moderate and severe BPD established by the National Institutes of Child Health and Human Development (NICHD) workshop. The participants have abnormal respiratory manifestations. 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: 28 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 Mesenchymal Stem Cell<br>Mesenchymal stem cell will be given to preterm infants with BPD. | Drug: Transplantation of mesenchymal stem cell<br>* Human umbilical cord-derived mesenchymal stem cell will be given to preterm infants through intravenous infusion. Dose A - 1 million cells per kg Dose B - 5 million cells per kg<br>* Other names: Intravenous infusion of mesenchymal stem cell;|
| Active Comparator: No Transplantation of Mesenchymal Stem Cell<br>Mesenchymal stem cell will be not given to preterm infants with BPD. | Drug: No transplantation of mesenchymal stem cell<br>* Human umbilical cord-derived mesenchymal stem cell will be not given to preterm infants through intravenous infusion.<br>* Other names: No intravenous infusion of mesenchymal stem cell;|

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 human umbilical cord -derived mesenchymal stem cells for BPD. | 24 hours after administration | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of high-resolution chest CT in participants | To evaluate the safety and efficacy of human umbilical cord -derived mesenchymal 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. | 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 heart rate in participants | To evaluate the safety of human umbilical cord -derived mesenchymal stem cells for BPD. | 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 | 
| Growth velocity (Z-score) in participants | To evaluate the safety and efficacy of human umbilical cord -derived mesenchymal stem cells for BPD. | within 2 years after administration | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Bronchopulmonary Dysplasia, human umbilical cord -derived mesenchymal stem cells