Clinical trial NCT02551003: Neuroprotective Effect of Autologous Cord Blood Combined With Therapeutic Hypothermia Following Neonatal Encephalopathy
Official title: A Multi-Centre Safety and Efficacy Study of Autologous Cord Blood Combined With Therapeutic Hypothermia Following Neonates Encephalopathy in China
Study type: INTERVENTIONAL
Overall status: WITHDRAWN
Phase: PHASE1
PHASE2
Conditions: Hypoxic Ischemic Encephalopathy
Cerebral Infarction
Lead sponsor: Children's Hospital of Fudan University
Sponsor class: OTHER
Collaborators: name: Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
name: Guangzhou Women and Children's Medical Center
First posted: 2015-09-16
Enrollment: 0
Sex: ALL
Maximum age (years): 24
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study examines the effect of cord blood in the treatment of newborn infants with neonatal encephalopathy in combination with hypothermia, which is the standard treatment for this condition. The hypothesis is that the cord blood + hypothermia combination will produce better neuroprotection than the standard treatment of hypothermia alone.

Detailed description: The primary aim of this study is to determine the neuroprotective effect of intravenous administration of autologous cord blood in neonates with severe encephalopathy (hypoxic ischemic encephalopathy or cerebral infarction). It is hypothesized that the administration of autologous cord blood will be safe and well tolerated in neonates with severe encephalopathy. If a neonate is born with signs of moderate to severe encephalopathy and cooled for the encephalopathy, the neonate will receive their own cord blood. The cord blood cells are divided into 3 doses and infused at 24, 48, and 72 hours after the birth. Infants will be randomised to treatment with autologous cord blood and hypothermia or hypothermia only and followed for safety and neurodevelopmental outcome up to 18 months. All infants in both groups will be treated with hypothermia for 72 hours started within 6 hours of delivery and infants who allocated to hypothermia and xenon will also receive autologous cord blood in 24 hours from birth through a purpose designed delivery system. Additionally, postnatal neuro-developmental outcomes in neonates with encephalopathy after autologous cord blood therapy will be measured; HIE injury to the neonate/infant brain post autologous cord blood therapy by imaging will be characterized; MRI's will be obtained per clinical routine; serum levels of selected cytokine and neurotrophic factors in neonates with HIE before and after autologous cord blood therapy will be compared and immune cell phenotype and function in neonates with HIE before and after autologous cord blood therapy will be compared.

Eligibility criteria: Inclusion Criteria:

1. Gestational age ≥ 34 weeks
2. Birth weight ≥ 1800 grams
3. 10-minute Apgar score ≤5 or continued need for ventilation or severe acidosis, defined as pH \<7.0
4. Moderate to severe encephalopathy (Sarnat II to III)
5. A moderately or severely abnormal background aEEG voltage, or seizures identified by aEEG, if monitored
6. Up to 24 hours of age
7. Autologous umbilical cord blood available to infuse 3 doses within 72 hours after birth
8. Parental informed consent

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 intrauterine growth restriction (weight \<1800g)
4. Severe infectious disease, such as sepsis
5. Inability to enroll by 24 hours of age
6. Volume of collected cord blood \<40 ml
7. Infants in extremis for whom no additional intensive therapy will be offered by attending neonatologist
8. Parents refuse consent

Primary outcomes:
measure: Mortality
timeFrame: From birth to the age of 18 months
measure: Disability Rate
timeFrame: From birth to the age of 18 months
Secondary outcomes:
measure: Neurodevelopment(Bayley Scores)
timeFrame: At the age of 12 months
measure: Neurodevelopment(Bayley Scores)
timeFrame: At the age of 18 months
measure: Brain Structural Alterations(MRI)
timeFrame: At the age of 7 days
measure: Brain Structural Alterations(MRI)
timeFrame: At the age of 28 days
measure: Brain Structural Alterations(MRI)
timeFrame: At the age of 12 months
measure: Brain Parenchyma Alterations(MRI)
timeFrame: At the age of 7 Days
measure: Brain Parenchyma Alterations(MRI)
timeFrame: At the age of 28 days
measure: Brain Parenchyma Alterations(MRI)
timeFrame: At the age of 12 months
measure: Intracranial Hemorrhage(MRI)
timeFrame: At the age of 7 days
measure: Intracranial Hemorrhage(MRI)
timeFrame: At the age of Day 28
measure: Intracranial Hemorrhage(MRI)
timeFrame: At the age of 12 months
measure: Number of Adverse Events
timeFrame: In 72 hours
measure: Number of Adverse Events(Blood Pressure)
timeFrame: In 72 hours
measure: Number of Adverse Events(Pulse)
timeFrame: In 72 hours
measure: Number of Adverse Events(Respiratory)
timeFrame: In 72 hours
measure: Incidence of Complication
timeFrame: From birth to the age of 28 days in each treatment period
measure: SDF-1 in Serum
timeFrame: At the age of 4 days
measure: SDF-1 in Serum
timeFrame: At the age of 14 days
measure: TNF-alpha in Serum
timeFrame: At the age of 4 days
measure: TNF-alpha in Serum
timeFrame: At the age of 14 days
measure: IL-1 in Serum
timeFrame: At the age of 4 days
measure: IL-1 in Serum
timeFrame: At the age of 14 days
Other outcomes:
Locations:
city: Shanghai
country: China
facility: Children Hospital of Fudan University
state: Shanghai
Study officials:
affiliation: Children's Hospital of Fudan University
name: Wenhao Zhou, Doctor
role: STUDY_CHAIR
References:
citation: Cotten CM, Murtha AP, Goldberg RN, Grotegut CA, Smith PB, Goldstein RF, Fisher KA, Gustafson KE, Waters-Pick B, Swamy GK, Rattray B, Tan S, Kurtzberg J. Feasibility of autologous cord blood cells for infants with hypoxic-ischemic encephalopathy. J Pediatr. 2014 May;164(5):973-979.e1. doi: 10.1016/j.jpeds.2013.11.036. Epub 2013 Dec 31.
citation: Walsh BH, Boylan GB, Livingstone V, Kenny LC, Dempsey EM, Murray DM. Cord blood proteins and multichannel-electroencephalography in hypoxic-ischemic encephalopathy. Pediatr Crit Care Med. 2013 Jul;14(6):621-30. doi: 10.1097/PCC.0b013e318291793f.
citation: Walsh BH, Broadhurst DI, Mandal R, Wishart DS, Boylan GB, Kenny LC, Murray DM. The metabolomic profile of umbilical cord blood in neonatal hypoxic ischaemic encephalopathy. PLoS One. 2012;7(12):e50520. doi: 10.1371/journal.pone.0050520. Epub 2012 Dec 5.
citation: Liao Y, Cotten M, Tan S, Kurtzberg J, Cairo MS. Rescuing the neonatal brain from hypoxic injury with autologous cord blood. Bone Marrow Transplant. 2013 Jul;48(7):890-900. doi: 10.1038/bmt.2012.169. Epub 2012 Sep 10.
citation: Pimentel-Coelho PM, Rosado-de-Castro PH, da Fonseca LM, Mendez-Otero R. Umbilical cord blood mononuclear cell transplantation for neonatal hypoxic-ischemic encephalopathy. Pediatr Res. 2012 Apr;71(4 Pt 2):464-73. doi: 10.1038/pr.2011.59. Epub 2012 Feb 8.
citation: Wiberg N, Kallen K, Herbst A, Olofsson P. Relation between umbilical cord blood pH, base deficit, lactate, 5-minute Apgar score and development of hypoxic ischemic encephalopathy. Acta Obstet Gynecol Scand. 2010 Oct;89(10):1263-9. doi: 10.3109/00016349.2010.513426.