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Hypoxic Ischemic EncephalopathyPhase 1/2NCT02551003

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

A Phase 1/2 study testing Autologous cord blood and Hypothermia in people with Hypoxic Ischemic Encephalopathy and Cerebral Infarction, run by Children's Hospital of Fudan University at 1 site in China.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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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. Read more about this study

Who is it for?
Ages Up to 24 hours
What is being tested?
Autologous cord blood and Hypothermia
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
1 siteChina
Study dates
8 Sep 2015to 30 Dec 2016
Phase
Phase 1/2
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages Up to 24 hours
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Gestational age ≥ 34 weeks
  • Birth weight ≥ 1800 grams
  • 10-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

Who cannot join

  • 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

Trial locations and contacts

1 site in 1 country.

China1 site
  • Children Hospital of Fudan University

    Shanghai, Shanghai Municipality, 201102

Other trials in China

About this study

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

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.

Read the 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.

Being tested
Autologous cord blood, Hypothermia
Medical subject headings
Hypoxia-Ischemia, Brain, Cerebral Infarction

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Autologous cord bloodDrug

    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.

  • HypothermiaDevice

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

Study groups in NCT02551003
Study groupRoleWhat they receive
Cord blood with hypothermiaExperimentalAutologous 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.
Receives: Drug: Autologous cord blood
HypothermiaActive comparatorHypothermia therapy of cooling to 33.5 ℃ body temperature for 72 hours and standard intensive care.
Receives: Device: Hypothermia

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Mortality

    The relative frequency of deaths in each group.

    Measured: From birth to the age of 18 months

  2. 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.

    Measured: From birth to the age of 18 months

Secondary outcomes (22)
  1. Neurodevelopment(Bayley Scores)

    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).

    Measured: At the age of 12 months

  2. Neurodevelopment(Bayley Scores)

    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).

    Measured: At the age of 18 months

  3. Brain Structural Alterations(MRI)

    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7.

    Measured: At the age of 7 days

  4. Brain Structural Alterations(MRI)

    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 28.

    Measured: At the age of 28 days

  5. Brain Structural Alterations(MRI)

    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on 12 months old.

    Measured: At the age of 12 months

  6. Brain Parenchyma Alterations(MRI)

    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7.

    Measured: At the age of 7 Days

  7. Brain Parenchyma Alterations(MRI)

    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 28.

    Measured: At the age of 28 days

  8. Brain Parenchyma Alterations(MRI)

    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on 12 months old.

    Measured: At the age of 12 months

  9. Intracranial Hemorrhage(MRI)

    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7.

    Measured: At the age of 7 days

  10. Intracranial Hemorrhage(MRI)

    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on Day 7.

    Measured: At the age of Day 28

  11. Intracranial Hemorrhage(MRI)

    Efficacy of cord blood by assessment of the changes in brain from baseline in MRI on 12 months.

    Measured: At the age of 12 months

  12. 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.

    Measured: In 72 hours

  13. 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.

    Measured: In 72 hours

  14. 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.

    Measured: In 72 hours

  15. 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.

    Measured: In 72 hours

  16. 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.

    Measured: From birth to the age of 28 days in each treatment period

  17. SDF-1 in Serum

    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.

    Measured: At the age of 4 days

  18. SDF-1 in Serum

    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.

    Measured: At the age of 14 days

  19. TNF-alpha in Serum

    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.

    Measured: At the age of 4 days

  20. TNF-alpha in Serum

    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.

    Measured: At the age of 14 days

  21. IL-1 in Serum

    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.

    Measured: At the age of 4 days

  22. IL-1 in Serum

    Biomarkers for Oxidative Stress, Inflammation and immune response as a measure of efficacy for hypoxic ischemic encephalopathy or cerebral infarction.

    Measured: At the age of 14 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 Sep 2015 (estimated)
  2. Study start8 Sep 2015
  3. Primary completion30 Dec 2016
  4. Study completion30 Dec 2016

Why it stopped: The study did not commence due to unforeseen challenges in securing adequate funding and resources, coupled with logistical constraints.

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1/2
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Parallel groups
Masking
Single blind
Who is masked
Participant
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02551003
Sponsor's protocol ID
CHFudanU_NNICU1
Status last verified
Dec 2023
First submitted
4 Sep 2015
Last updated
29 Dec 2023
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 24388332
  • 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.

    PubMed 23823198
  • 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.

    PubMed 23227182
  • 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.

    PubMed 22964590
  • 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.

    PubMed 22430382
  • 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.

    PubMed 20846059

Questions about this trial

What is this clinical trial studying?

A Phase 1/2 study testing Autologous cord blood and Hypothermia in people with Hypoxic Ischemic Encephalopathy and Cerebral Infarction, run by Children's Hospital of Fudan University at 1 site in China.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 8 inclusion and 8 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: withdrawn, as of the sponsor's last update on 29 Dec 2023. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in China. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this combined phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

The study was withdrawn before enrolling participants, so there are no results.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Mortality (time frame: From birth to the age of 18 months). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02551003, which also lists 6 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 29 Dec 2023.

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