Neural Progenitor Cell and Paracrine Factors to Treat Hypoxic Ischemic Encephalopathy

Study Overview
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Brief Summary
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The purpose of this study is to investigate the efficacy and safety of allogenic neural progenitor cell and paracrine factors of human mesenchymal stem cells for patients with moderate/severe Hypoxic-Ischemic Encephalopathy

Detailed Description
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Neonates diagnosed moderate/severe Hypoxic-Ischemic Encephalopathy after birth will receive routine therapy and be randomized to four arms for allogenic neural progenitor cells transplantation，paracrine factors of human mesenchymal stem cells intrathecal injection，combination of cell and factor or only routine therapy. Patients will be followed for neurodevelopmental outcome at 12 and 18 months in Pediatrics of Navy General Hospital. Magnetic Resonance Imaging, electroencephalogram, Bailey scores, Peabody development measure scale and Gross motor function measure assessment will be obtained in the following research.Results will be analyzed and described in study reports.

Official Title
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Safety and Efficacy Study of Neural Progenitor Cell Transplantation and Paracrine Factors From Human Mesenchymal Stem Cells to Treat Newborn With Hypoxic-ischemic Encephalopathy

Conditions
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Hypoxic-Ischemic Encephalopathy

Intervention / Treatment
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* Biological: neural progenitor cell
* Biological: Paracrine factors
* Biological: progenitor cell and paracrine factors


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: gestational age ≥ 34weeks, body weight ≥ 2kg. 1 minute apgar score ≤3, and 5 minutes apgar score ≤5, OR umbilical arterial blood gas potential of hydrogen<7.0, OR 30 minutes base excess≤-12 mmol/L, OR need for ventilation 5 minutes after birth. All infants must have signs of encephalopathy (such as convulsion, coma, dystonia, abnormal primitive reflex and irregular respiration) within 6 hours of age or continued abnormal EEG for more than 24h. Exclusion Criteria: Does not meet the inclusion criteria Suffer from other serious organic disease or congenital, hereditary metabolic diseases Intracranial active infection, or neuromuscular damage outside central nervous system potential of hydrogen / electrolyte disorders without improvement or stability Coagulation disorders associated with bleeding tendency Immune function is not perfect Patients or his guardian refuse consent. Patients or his guardian don't accept the follow-up schedule.

Ages Eligible for Study
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Minimum Age: 1 Day
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: Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Neural progenitor cell<br>Three doses of Neural progenitor cell (4*10^6) intrathecally at 48-72h, 5d and 10d after birth.+routine therapy | Biological: neural progenitor cell<br>* Neural progenitor cells are derived from the same aborted human fetal forebrain.<br>|
| Experimental: Paracrine factors<br>Three doses of concentrated paracrine factors of human mesenchymal stem cell （0.5ml） intrathecally at 12h,24h,48h after birth.+routine therapy | Biological: Paracrine factors<br>* The factors obtained from cultured human mesenchymal stem cells were concentrated 50 times<br>* Other names: paracrine factor of human mesenchymal stem cells;|
| Experimental: Progenitor cell and paracrine factors<br>Three doses of concentrated paracrine factors 0.5ml intrathecally at 12h,24h,48h after birth.And three doses of neural progenitor cell (4*10^6) intrathecally at 48-72h, 5d and 10d after birth.+routine therapy | Biological: progenitor cell and paracrine factors<br>* Neural progenitor cells will be received after paracrine factors therapy<br>|
| No Intervention: Routine therapy<br>neonates only receive routine therapy | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Neonatal Behavioral Neurological Assessment |  | 14days after birth | 
| number of adverse events | adverse events like fever、infection、seizures、hemorrhage coursed by interventions | 7days after cell or factor injection | 
| Neonatal Behavioral Neurological Assessment |  | 28days after birth | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Bayley score | Gross motor function measure assessment for children diagnosed cerebral palsy | 12 months after birth | 
| Bayley score | Gross motor function measure assessment for children diagnosed cerebral palsy | 18 months after birth | 
| Peabody development measure scale | Gross motor function measure assessment for children diagnosed cerebral palsy | 12 months after birth | 
| Peabody development measure scale | Gross motor function measure assessment for children diagnosed cerebral palsy | 18 months after birth | 
| Number of death |  | 1 years after birth | 
| Number of participants with treatment-related central nervous tumor as assessed by Magnetic Resonance Imaging or CT |  | 5 years after birth | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hypoxic-Ischemic Encephalopathy, progenitor cell, paracrine factor, adipose mesenchymal stem cell, neonate