Neuroprotective Effect of Autologous Cord Blood Combined With Therapeutic Hypothermia Following Neonatal Encephalopathy

Cerebral Infarction Clinical Trial

Official title:

A Multi-Centre Safety and Efficacy Study of Autologous Cord Blood Combined With Therapeutic Hypothermia Following Neonates Encephalopathy in China

Clinical Trial Details — Status: Not yet recruiting

Administrative data

• NCT number: NCT02605018
• Other study ID #: PHDehong_NNICU1
• Status: Not yet recruiting
• Phase: Phase 1/Phase 2
• First received: November 9, 2015
• Last updated: November 11, 2015
• Start date: November 2015
• Est. completion date: December 2018

Study information

• Verified date: November 2015
• Source: The People's Hospital of Dehong Autonomous Prefecture
• Contact: Zhaoqing Yin, bachelor
• Email: zhaoqingyin99[@]sina.com
• Is FDA regulated: No
• Health authority: China: Health and Family planning commision Dehong Autonomous Prefecture of Dai and Jingpo Ethnic Groups,Yunnnan Province
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Not yet recruiting
• Enrollment: 60
• Est. completion date: December 2018
• Est. primary completion date: November 2018
• Accepts healthy volunteers: No
• Gender: Both
• Age group: N/A to 24 Hours

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Brain Diseases
• Brain Ischemia
• Cerebral Infarction
• Hypothermia
• Hypoxia-Ischemia, Brain
• Hypoxic Ischemic Encephalopathy

Intervention

Drug:
• Autologous cord blood
Autologous cord blood will be collected after birth and administered in divided aliquots during the first 3 days of life. At the same time, babies will referred to neonatal intensive care unit for hypothermia therapy of cooling to 33.5 ? body temperature for 72 hours and standard intensive care.

Device:
• Hypothermia
Hypothermia therapy of cooling to 33.5 ? body temperature for 72 hours and standard intensive care.

Locations

Country	Name	City	State
n/a

Sponsors (4)

Lead Sponsor	Collaborator
The People's Hospital of Dehong Autonomous Prefecture	Children's Hospital of Fudan University, Guangzhou Women and Children's Medical Center, Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region

References & Publications (6)

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. — View 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. Review. — View 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. Review. — View 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. — View 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. — View Citation

Wiberg N, Källén 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Mortality	The relative frequency of deaths in each group.	From birth to the age of 18 months	No
Primary	Disability Rate	Disability, defined as a physical or mental handicap, especially one that prevents a person from living a full, normal life or from holding a gainful job.	From birth to the age of 18 months	No
Secondary	Neurodevelopment	Efficacy of levetiracetam by assessment of the change from baseline to 12 months in neurodevelopment via Bayley Scores of Infant Development Mental Development Index(BSID).	At the age of 12 months	No
Secondary	Neurodevelopment	Efficacy of levetiracetam by assessment of the change from baseline to 18 months in neurodevelopment via Bayley Scores of Infant Development Mental Development Index (BSID).	At the age of 18 months	No
Secondary	Brain Structural Alterations(MRI)	Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7.	At the age of 7 days	No
Secondary	Brain Structural Alterations(MRI)	Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 28.	At the age of 28 days	No
Secondary	Brain Structural Alterations(MRI)	Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on 12 months old.	At the age of 12 months	No
Secondary	Brain Parenchyma Alterations(MRI)	Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7.	At the age of 7 Days	No
Secondary	Brain Parenchyma Alterations(MRI)	Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 28.	At the age of 28 days	No
Secondary	Brain Parenchyma Alterations(MRI)	Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on 12 months old.	At the age of 12 months	No
Secondary	Intracranial Hemorrhage(MRI)	Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7.	At the age of 7 days	No
Secondary	Intracranial Hemorrhage(MRI)	Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 28.	At the age of Day 28	No
Secondary	Intracranial Hemorrhage(MRI)	Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on 12 months.	At the age of 12 months	No
Secondary	Number of Adverse Events	This is a composition of general appearance includes abdomen, skin, head and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.	In 72 hours	No
Secondary	Number of Adverse Events(Blood Pressure)	This is a composition of general appearance, blood pressure, pulse, respiratory, cardiovascular, abdomen, skin, head and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.	In 72 hours	No
Secondary	Number of Adverse Events(Pulse)	This is a composition of general appearance, blood pressure, pulse, respiratory, cardiovascular, abdomen, skin, head and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.	In 72 hours	No
Secondary	Number of Adverse Events(Respiratory)	This is a composition of general appearance, blood pressure, pulse, respiratory, cardiovascular, abdomen, skin, head and neck (including ears, eyes, nose, and throat), lymph nodes, thyroid, musculoskeletal and neurological systems.	In 72 hours	No
Secondary	Incidence of Complication	To gain the incidence of Polycythemia,neutropenia,thrombocytopenia,hypertension, sepsis,intraventricular hemorrhage(IVH), periventricular leukomalacia(PVL), seizure, necrotizing enterocolitis (NEC), persistent ductus arterious (PDA), apnea of prematurity, pulmonary haemorrhage, pulmonary hypertension, Prolonged blood coagulation time, retinopathy of prematurity(ROP), cardiac arrhythmia, major venous thrombosis, Renal failure treated with dialysis, pneumonia, pulmonary airleak and chronic lung disease.	From birth to the age of 28 days in each treatment period	No
Secondary	SDF-1 in Serum	Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.	At the age of 4 days	Yes
Secondary	SDF-1 in Serum	Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.	At the age of 14 days	Yes
Secondary	TNF-alpha in Serum	Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.	At the age of 4 days	Yes
Secondary	TNF-alpha in Serum	Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.	At the age of 14 days	Yes
Secondary	IL-1 in Serum	Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.	At the age of 4 days	Yes
Secondary	IL-1 in Serum	Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.	At the age of 14 days	Yes