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

December 27, 2023 updated by: Children's Hospital of Fudan University

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.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Withdrawn

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

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 Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • China
    • Shanghai
      • Shanghai, Shanghai, China, 201102
        • Children Hospital of Fudan University

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

No older than 1 day (Child)

Accepts Healthy Volunteers

No

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Parallel Assignment
  • Masking: Single

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
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.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Measure Description
Time Frame
Mortality
Time Frame: From birth to the age of 18 months
The relative frequency of deaths in each group.
From birth to the age of 18 months
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.
From birth to the age of 18 months

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Measure Description
Time Frame
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).
At the age of 12 months
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).
At the age of 18 months
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.
At the age of 7 days
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.
At the age of 28 days
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.
At the age of 12 months
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.
At the age of 7 Days
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.
At the age of 28 days
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.
At the age of 12 months
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.
At the age of 7 days
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.
At the age of Day 28
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.
At the age of 12 months
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.
In 72 hours
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.
In 72 hours
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.
In 72 hours
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.
In 72 hours
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.
From birth to the age of 28 days in each treatment period
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.
At the age of 4 days
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.
At the age of 14 days
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.
At the age of 4 days
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.
At the age of 14 days
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.
At the age of 4 days
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.
At the age of 14 days

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
Children's Hospital of Fudan University

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Guangzhou Women and Children's Medical Center
Maternal and Child Health Hospital of Guangxi Zhuang Autonomous Region

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Chair: Wenhao Zhou, Doctor, Children's Hospital of Fudan University

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
September 8, 2015

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
December 30, 2016

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
December 30, 2016

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
September 4, 2015

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
September 14, 2015

First Posted (Estimated)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
September 16, 2015

Study Record Updates

Last Update Posted (Actual)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
December 29, 2023

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 27, 2023

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
December 1, 2023

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • CHFudanU_NNICU1

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