Clinical trial NCT02256618: Autologous Cord Blood Cell Therapy for Neonatal Encephalopathy
Official title: A Pilot Feasibility and Safety Study of Autologous Umbilical Cord Blood Cell Therapy in Infants With Neonatal Encephalopathy
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
Conditions: Neonatal Encephalopathy
Hypoxic-ischemic Encephalopathy
Keywords: neonatal encephalopathy
hypoxic-ischemic encephalopathy
newborn infants
neonates
umbilical cord blood cells
Lead sponsor: Neonatal Encephalopathy Consortium, Japan
Sponsor class: NETWORK
Collaborators: name: Osaka City University
name: Yodogawa Christian Hospital
name: Kurashiki Central Hospital
name: Nagoya University
name: Osaka City General Hospital
name: Saitama Medical University
name: National Cerebral and Cardiovascular Center, Japan
name: National Center for Child Health and Development, Japan
name: Tokyo University
name: Tokyo Women's Medical University
First posted: 2014-10-03
Enrollment: 6
Sex: ALL
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief 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.

Detailed 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.

Eligibility criteria: 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

Primary outcomes:
measure: Adverse event rates
timeFrame: first 30 postnatal days
Secondary outcomes:
measure: Efficacy
timeFrame: 18 months
Other outcomes:
Locations:
city: Nagoya
country: Japan
facility: Nagoya University Hospital
state: Aichi
city: Kurashiki
country: Japan
facility: Kurashiki Central Hospital
state: Okayama
city: Kawagoe
country: Japan
facility: Saitama Medical University
state: Saitama
city: Osaka
country: Japan
facility: Yodogawa Christian Hospital
city: Osaka
country: Japan
facility: Osaka City General Hospital
city: Osaka
country: Japan
facility: Osaka City University
Study officials:
affiliation: Osaka City University
name: Haruo Shintaku, MD, PhD
role: STUDY_DIRECTOR
References:
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.
citation: 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.
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. doi: 10.1172/JCI20622.