Autologous Cord Blood Cell Therapy for Neonatal Encephalopathy

Hypoxic-ischemic Encephalopathy Clinical Trial

Official title:

A Pilot Feasibility and Safety Study of Autologous Umbilical Cord Blood Cell Therapy in Infants With Neonatal Encephalopathy

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02256618
• Other study ID #: UMIN000014903
• Status: Completed
• Phase: Phase 1
• Start date: August 2014
• Est. completion date: July 2019

Study information

• Verified date: October 2019
• Source: Neonatal Encephalopathy Consortium, Japan
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

This is a pilot study to test feasibility and safety of intravenous infusion of autologous umbilical cord blood cells in the first 72 hours after birth if a neonate is born with signs of encephalopathy.

Description:

This is a multicenter pilot study to evaluate the feasibility and safety of intravenous infusions of autologous (the patient's own) umbilical cord blood cells in term gestation newborns with neonatal encephalopathy (hypoxic-ischemic encephalopathy). If a neonate is born with signs of moderate to severe encephalopathy and cooled for the encephalopathy, the neonate can receive their own non-cryopreserved volume- and red blood cell-reduced cord blood cells. The cord blood cells are divided into 3 doses and infused at 12-24, 36-48, and 60-72 hours after the birth. Infants will be followed for safety and neurodevelopmental outcome up to 18 months.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 6
• Est. completion date: July 2019
• Est. primary completion date: October 2017
• Accepts healthy volunteers: No
• Gender: All
• Age group: N/A to 24 Hours

Eligibility

Inclusion Criteria:

Infants are eligible if they meet all the following inclusion criteria except 4.

1. =36 weeks gestation

2. Either a 10-minute Apgar score =5, continued need for resuscitation for at least 10 minutes, or severe acidosis, defined as pH <7.0 or base deficit =16 mmol/L in a sample of umbilical cord blood or any blood during the first hour after birth

3. Moderate to severe encephalopathy (Sarnat II to III)

4. A moderately or severely abnormal background amplitude-integrated EEG (aEEG) voltage, or seizures identified by aEEG, if monitored

5. Up to 24 hours of age

6. Autologous umbilical cord blood available to infuse within 3 days after birth

7. A person with parental authority must have consented for the study.

Exclusion Criteria:

1. Known major congenital anomalies, such as chromosomal anomalies, heart diseases

2. Major intracranial hemorrhage identified by brain ultrasonography or computed tomography

3. Severe growth restriction, with birth-weight less than 1800 g

4. Severe infectious disease, such as sepsis

5. Hyperkalemia

6. Outborn infants (Infants born at hospitals other than the study sites)

7. Volume of collected cord blood <40 ml

8. Infants judged critically ill and unlikely to benefit from neonatal intensive care by the attending neonatologist

Related Conditions & MeSH terms

• Brain Diseases
• Brain Ischemia
• Hypoxia-Ischemia, Brain
• Hypoxic-ischemic Encephalopathy
• Neonatal Encephalopathy

Intervention

Other:
• Autologous umbilical cord blood cells
Autologous non-cryopreserved volume- and red blood cell-reduced cord blood cells will be intravenously infused

Locations

Country	Name	City	State
Japan	Saitama Medical University	Kawagoe	Saitama
Japan	Kurashiki Central Hospital	Kurashiki	Okayama
Japan	Nagoya University Hospital	Nagoya	Aichi
Japan	Osaka City General Hospital	Osaka
Japan	Osaka City University	Osaka
Japan	Yodogawa Christian Hospital	Osaka

Sponsors (11)

Lead Sponsor	Collaborator
Neonatal Encephalopathy Consortium, Japan	Kurashiki Central Hospital, Nagoya University, National Center for Child Health and Development, Japan, National Cerebral and Cardiovascular Center, Osaka City General Hospital, Osaka City University, Saitama Medical University, Tokyo University, Tokyo Women's Medical University, Yodogawa Christian Hospital

Country where clinical trial is conducted

Japan, 

References & Publications (3)

Ohshima M, Taguchi A, Tsuda H, Sato Y, Yamahara K, Harada-Shiba M, Miyazato M, Ikeda T, Iida H, Tsuji M. Intraperitoneal and intravenous deliveries are not comparable in terms of drug efficacy and cell distribution in neonatal mice with hypoxia-ischemia. Brain Dev. 2015 Apr;37(4):376-86. doi: 10.1016/j.braindev.2014.06.010. Epub 2014 Jul 14. — View Citation

Taguchi A, Soma T, Tanaka H, Kanda T, Nishimura H, Yoshikawa H, Tsukamoto Y, Iso H, Fujimori Y, Stern DM, Naritomi H, Matsuyama T. Administration of CD34+ cells after stroke enhances neurogenesis via angiogenesis in a mouse model. J Clin Invest. 2004 Aug;114(3):330-8. — View Citation

Tsuji M, Taguchi A, Ohshima M, Kasahara Y, Sato Y, Tsuda H, Otani K, Yamahara K, Ihara M, Harada-Shiba M, Ikeda T, Matsuyama T. Effects of intravenous administration of umbilical cord blood CD34(+) cells in a mouse model of neonatal stroke. Neuroscience. 2014 Mar 28;263:148-58. doi: 10.1016/j.neuroscience.2014.01.018. Epub 2014 Jan 18. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Adverse event rates	Adverse event rates (combined rate of death, continuous respiratory support, and continuous use of vasopressor) will be compared between the cell recipients and historical controls at 30 days of age.	first 30 postnatal days
Secondary	Efficacy	Neuroimaging at 12 months of age and neurodevelopmental function at 18 months of age will be compared between the cell recipients and historical controls.	18 months