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

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ClinicalTrials.gov Identifier: NCT02551003
Recruitment Status : Recruiting
First Posted : September 16, 2015
Last Update Posted : October 30, 2018
Sponsor:
Collaborators:
Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
Guangzhou Women and Children's Medical Center
Information provided by (Responsible Party):
Children's Hospital of Fudan University

Study Description
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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.

Condition or disease Intervention/treatment Phase
Hypoxic Ischemic Encephalopathy Cerebral Infarction Drug: Autologous cord blood Device: Hypothermia Phase 1 Phase 2

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.

Study Design
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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single (Participant)
Primary Purpose: Treatment
Official Title: A Multi-Centre Safety and Efficacy Study of Autologous Cord Blood Combined With Therapeutic Hypothermia Following Neonates Encephalopathy in China
Actual Study Start Date : September 8, 2015
Estimated Primary Completion Date : December 30, 2018
Estimated Study Completion Date : December 30, 2018

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Hypothermia

Arms and Interventions
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Arm Intervention/treatment
Experimental: Cord blood with hypothermia
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
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.
Active Comparator: Hypothermia
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.


Outcome Measures
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Primary Outcome Measures :
  1. Mortality [ Time Frame: From birth to the age of 18 months ]
    The relative frequency of deaths in each group.

  2. Disability Rate [ Time Frame: From birth to the age of 18 months ]
    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.


Secondary Outcome Measures :
  1. Neurodevelopment(Bayley Scores) [ Time Frame: At the age of 12 months ]
    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).

  2. Neurodevelopment(Bayley Scores) [ Time Frame: At the age of 18 months ]
    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).

  3. Brain Structural Alterations(MRI) [ Time Frame: At the age of 7 days ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7.

  4. Brain Structural Alterations(MRI) [ Time Frame: At the age of 28 days ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 28.

  5. Brain Structural Alterations(MRI) [ Time Frame: At the age of 12 months ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on 12 months old.

  6. Brain Parenchyma Alterations(MRI) [ Time Frame: At the age of 7 Days ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7.

  7. Brain Parenchyma Alterations(MRI) [ Time Frame: At the age of 28 days ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 28.

  8. Brain Parenchyma Alterations(MRI) [ Time Frame: At the age of 12 months ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on 12 months old.

  9. Intracranial Hemorrhage(MRI) [ Time Frame: At the age of 7 days ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7.

  10. Intracranial Hemorrhage(MRI) [ Time Frame: At the age of Day 28 ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7.

  11. Intracranial Hemorrhage(MRI) [ Time Frame: At the age of 12 months ]
    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on 12 months.

  12. Number of Adverse Events [ Time Frame: In 72 hours ]
    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.

  13. Number of Adverse Events(Blood Pressure) [ Time Frame: In 72 hours ]
    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.

  14. Number of Adverse Events(Pulse) [ Time Frame: In 72 hours ]
    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.

  15. Number of Adverse Events(Respiratory) [ Time Frame: In 72 hours ]
    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.

  16. Incidence of Complication [ Time Frame: From birth to the age of 28 days in each treatment period ]
    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.

  17. SDF-1 in Serum [ Time Frame: At the age of 4 days ]
    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.

  18. SDF-1 in Serum [ Time Frame: At the age of 14 days ]
    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.

  19. TNF-alpha in Serum [ Time Frame: At the age of 4 days ]
    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.

  20. TNF-alpha in Serum [ Time Frame: At the age of 14 days ]
    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.

  21. IL-1 in Serum [ Time Frame: At the age of 4 days ]
    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.

  22. IL-1 in Serum [ Time Frame: At the age of 14 days ]
    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.


Eligibility Criteria
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Ages Eligible for Study:   up to 24 Hours   (Child)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
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
Contacts and Locations
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Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02551003


Contacts
Contact: Wenhao Zhou, Doctor zwhchfu@126.com
Contact: Guoqiang Cheng, Doctor gqchengcm@163.com

Locations
China, Shanghai
Children Hospital of Fudan University Recruiting
Shanghai, Shanghai, China, 201102
Contact: Wenhao Zhou, Doctor    (+86)021-64931003    zwhchfu@126.com   
Sponsors and Collaborators
Children's Hospital of Fudan University
Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region
Guangzhou Women and Children's Medical Center
Investigators
Study Chair: Wenhao Zhou, Doctor Children's Hospital of Fudan University
More Information
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Publications:

Responsible Party: Children's Hospital of Fudan University
ClinicalTrials.gov Identifier: NCT02551003     History of Changes
Obsolete Identifiers: NCT02605018
Other Study ID Numbers: CHFudanU_NNICU1
First Posted: September 16, 2015    Key Record Dates
Last Update Posted: October 30, 2018
Last Verified: October 2018

Additional relevant MeSH terms:
Infarction
Hypothermia
Brain Diseases
Cerebral Infarction
Brain Ischemia
Hypoxia-Ischemia, Brain
Ischemia
Pathologic Processes
Necrosis
Body Temperature Changes
Signs and Symptoms
 Central Nervous System Diseases
Nervous System Diseases
Brain Infarction
Cerebrovascular Disorders
Stroke
Vascular Diseases
Cardiovascular Diseases
Hypoxia, Brain
Neuroprotective Agents
Protective Agents
Physiological Effects of Drugs