Neural Progenitor Cell and Paracrine Factors to Treat Hypoxic Ischemic Encephalopathy

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

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

Study Overview

• Status: Unknown
• Conditions: Hypoxic-Ischemic Encephalopathy
• Intervention / Treatment: Biological: neural progenitor cell; Biological: Paracrine factors; Biological: progenitor cell and paracrine factors

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 120
• Phase: Not Applicable

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100048
    • Recruiting
    • Navy General Hospital
    • Principal Investigator: Zuo Luan, MD
    • Sub-Investigator: Weipeng Liu, MD
    • Contact: Zuo Luan, MD; Phone Number: 18600310270; Email: hjzyyerke@163.com
    • Contact: Weipeng Liu, MD; Phone Number: 135581797015; Email: hjzyynicu@163.com
  • Beijing
    • Beijing, Beijing, China, 100048
      • Recruiting
      • Navy General Hospital
      • Contact: Zuo Luan, MD; Email: hjzyyerke@163.com
      • Principal Investigator: Zuo Luan, MD
      • Sub-Investigator: Weipeng Liu, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 day to 2 weeks (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. gestational age ≥ 34weeks, body weight ≥ 2kg.
2. 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.
3. 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:

1. Does not meet the inclusion criteria
2. Suffer from other serious organic disease or congenital, hereditary metabolic diseases
3. Intracranial active infection, or neuromuscular damage outside central nervous system
4. potential of hydrogen / electrolyte disorders without improvement or stability
5. Coagulation disorders associated with bleeding tendency
6. Immune function is not perfect
7. Patients or his guardian refuse consent.
8. Patients or his guardian don't accept the follow-up schedule.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

4

Arms and Interventions

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

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: Navy General Hospital, Beijing
• Collaborators: Daping Hospital and the Research Institute of Surgery of the Third Military Medical University; Bethune International Peace Hospital; Hunan Children's Hospital; Shangluo Central Hospital; 252 Military Hospital
• Investigators: Study Chair: Zuo Luan, MD, Navy General Hosiptal

Publications and helpful links

General Publications

• Luan Z, Liu W, Qu S, Du K, He S, Wang Z, Yang Y, Wang C, Gong X. Effects of neural progenitor cell transplantation in children with severe cerebral palsy. Cell Transplant. 2012;21 Suppl 1:S91-8. doi: 10.3727/096368912X633806.
• Bruschettini M, Romantsik O, Moreira A, Ley D, Thebaud B. Stem cell-based interventions for the prevention of morbidity and mortality following hypoxic-ischaemic encephalopathy in newborn infants. Cochrane Database Syst Rev. 2020 Aug 19;8(8):CD013202. doi: 10.1002/14651858.CD013202.pub2.

Study record dates

Study Major Dates

• Study Start: January 1, 2013
• Primary Completion (Anticipated): July 1, 2017
• Study Completion (Anticipated): December 1, 2017

Study Registration Dates

• First Submitted: April 27, 2014
• First Submitted That Met QC Criteria: July 30, 2016
• First Posted (Estimate): August 3, 2016

Study Record Updates

• Last Update Posted (Estimate): August 3, 2016
• Last Update Submitted That Met QC Criteria: July 30, 2016
• Last Verified: July 1, 2016

More Information

Terms related to this study

• Keywords: progenitor cell; neonate; Hypoxic-Ischemic Encephalopathy; paracrine factor; adipose mesenchymal stem cell
• Additional Relevant MeSH Terms: Pathologic Processes; Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Hypoxia, Brain; Brain Ischemia; Ischemia; Brain Diseases; Hypoxia; Hypoxia-Ischemia, Brain
• Other Study ID Numbers: NavyGHB-P-01

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No