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

Recruiting

Phase 1/2 Results N/A

Trial Description

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.

Conditions

Interventions

  • Hypothermia Device
    Intervention Desc: Hypothermia therapy of cooling to 33.5 ℃ body temperature for 72 hours and standard intensive care.
    ARM 1: Kind: Experimental
    Label: Hypothermia
    Description: 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.
  • Autologous cord blood Drug
    Intervention Desc: 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.
    ARM 1: Kind: Experimental
    Label: Cord blood with hypothermia
    Description: Autologous cord blood will be collected after birth and stored in Blood Center of Dehong Autonomous Prefecture. 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 room temperature 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 be referred to neonatal intensive care unit for hypothermia therapy of cooling to 33.5 ℃ body temperature for 72 hours and standard intensive care.

Trial Design

  • Allocation: Randomized
  • Masking: Single Blind (Subject)
  • Purpose: Treatment
  • Endpoint: Safety/Efficacy Study
  • Intervention: Parallel Assignment

Outcomes

Type Measure Time Frame Safety Issue
Primary Mortality From birth to the age of 18 months No
Primary Disability Rate From birth to the age of 18 months No
Secondary Neurodevelopment At the age of 12 months No
Secondary Brain Structural Alterations(MRI) At the age of 7 days No
Secondary Brain Parenchyma Alterations(MRI) At the age of 7 Days No
Secondary Intracranial Hemorrhage(MRI) At the age of 7 days No
Secondary Number of Adverse Events In 72 hours No
Secondary Number of Adverse Events(Blood Pressure) In 72 hours No
Secondary Number of Adverse Events(Pulse) In 72 hours No
Secondary Number of Adverse Events(Respiratory) In 72 hours No
Secondary Incidence of Complication From birth to the age of 28 days in each treatment period No
Secondary SDF-1 in Serum At the age of 4 days Yes
Secondary TNF-alpha in Serum At the age of 4 days Yes
Secondary IL-1 in Serum At the age of 4 days Yes
Secondary Neurodevelopment(Bayley Scores) At the age of 12 months No

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