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

NCT02551003 | Withdrawn Phase 1 DMC

• 1 other identifier: CHFudanU_NNICU1
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

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.

Conditions

Hypoxic Ischemic Encephalopathy; Cerebral Infarction

Outcome Measures

Primary Outcomes (2)

• Mortality

  The relative frequency of deaths in each group.

  From birth to the age of 18 months

• 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

Secondary Outcomes (22)

• Neurodevelopment(Bayley Scores)

  At the age of 12 months

• Neurodevelopment(Bayley Scores)

  At the age of 18 months

• Brain Structural Alterations(MRI)

  At the age of 7 days

• Brain Structural Alterations(MRI)

  At the age of 28 days

• Brain Structural Alterations(MRI)

  At the age of 12 months

Study Arms (2)

Cord blood with hypothermia

EXPERIMENTAL

Autologous cord blood will be collected after birth and stored in Cord Blood Bank of hospital. All cord blood samples are routinely performed by dedicated, trained UCB collection staff and is restricted to deliveries of mothers who have given prior written informed consent for collection. If the mother delivered a baby with signs of HIE or cerebral infarction, Bank staff collected UCB utilizing standard procedures. Collected UCB was transported at roomtemperature in validated shippers to the NICU. Infusions were started when cells and study staff were available for administration and monitoring. Infants received up to 3 infusions, with the first dose as soon as possible after birth, and at, 48, and 72 postnatal hours. 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.

Drug: Autologous cord blood

Hypothermia

ACTIVE COMPARATOR

Hypothermia therapy of cooling to 33.5 ℃ body temperature for 72 hours and standard intensive care.

Device: Hypothermia

Interventions

Autologous cord blood DRUG

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.

Cord blood with hypothermia

Hypothermia DEVICE

Hypothermia therapy of cooling to 33.5 ℃ body temperature for 72 hours and standard intensive care.

Hypothermia

Eligibility Criteria

• Age: Up to 24 Hours
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

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

You may not qualify if:

• Known major congenital anomalies, such as chromosomal anomalies, heart diseases
• Major intracranial hemorrhage identified by brain ultrasonography or computed tomography
• Severe intrauterine growth restriction (weight \<1800g)
• Severe infectious disease, such as sepsis
• Inability to enroll by 24 hours of age
• Volume of collected cord blood \<40 ml
• Infants in extremis for whom no additional intensive therapy will be offered by attending neonatologist
• Parents refuse consent

Sponsors & Collaborators

• Children's Hospital of Fudan University: lead
• Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region: collaborator
• Guangzhou Women and Children's Medical Center: collaborator

Study Sites (1)

Children Hospital of Fudan University

Shanghai, Shanghai Municipality, 201102, China

Location

Related 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.

  PMID: 24388332 BACKGROUND

• 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.

  PMID: 23823198 BACKGROUND

• 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.

  PMID: 23227182 BACKGROUND

• 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.

  PMID: 22964590 BACKGROUND

• 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.

  PMID: 22430382 BACKGROUND

• 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.

  PMID: 20846059 BACKGROUND

MeSH Terms

Conditions

Hypoxia-Ischemia, Brain; Cerebral Infarction

Condition Hierarchy (Ancestors)

Brain Ischemia; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Hypoxia, Brain; Vascular Diseases; Cardiovascular Diseases; Hypoxia; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Brain Infarction; Stroke; Infarction; Ischemia; Pathologic Processes; Necrosis

Study Officials

• Wenhao Zhou, Doctor

  Children's Hospital of Fudan University

  STUDY CHAIR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 4, 2015
• First Posted: September 16, 2015
• Study Start: September 8, 2015
• Primary Completion: December 30, 2016
• Study Completion: December 30, 2016
• Last Updated: December 29, 2023

Record last verified: 2023-12

Locations

CN (1)