Cytokines Associated With Cord Blood Cell Therapy for Neonatal Encephalopathy

A Study to Determine if Autologous Umbilical Cord Blood Cell Therapy Alters Serum Levels of Cytokines and Trophic Factors in Neonatal Encephalopathy

This is a observational study to assess the effects of and to explore the mechanisms of autologous umbilical cord blood cell therapy for neonatal encephalopathy by way of measuring serum cytokines.

Study Overview

• Status: Unknown
• Conditions: Neonatal Encephalopathy (Neonatal Hypoxic-ischemic Encephalopathy)
• Intervention / Treatment: Biological: Autologous cord blood cell therapy

Detailed Description

The effects and mechanisms of umbilical cord blood cell therapy for perinatal brain injury are not well understood. This is a multicenter study to measure serum levels of inflammatory cytokines and trophic factors associated with perinatal brain injury and repair in term gestation newborns with neonatal encephalopathy (hypoxic-ischemic encephalopathy). This study proceeds along with the study "Autologous cord blood cell therapy for neonatal encephalopathy (ClinicalTrials.gov identifier: NCT02256618)". Blood samples are obtained before the first cell infusion, and subsequently 2h, 24h, 48h, and 7 days after the first cell infusion. Blood samples are obtained in the same manner from newborns with neonatal encephalopathy who are not receiving the cell therapy.

• Study Type: Observational
• Enrollment (Anticipated): 18

Contacts and Locations

Study Locations

• Japan
  • Osaka, Japan, 534-0021
    • Osaka City General Hospital
  • Osaka, Japan, 533-0032
    • Yodogawa Christian Hospital
  • Osaka, Japan, 545-8585
    • Osaka City University Hospital
  • Aichi
    • Nagoya, Aichi, Japan, 466-8560
      • Nagoya University Hospital
  • Okayama
    • Kurashiki, Okayama, Japan, 710-8602
      • Kurashiki Central Hospital
  • Saitama
    • Kawagoe, Saitama, Japan, 350-0495
      • Saitama Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 1 day (CHILD)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Infants with encephalopathy who meet the inclusion criteria of therapeutic hypothermia, either those who receive the cell therapy or those who do not.

Description

Inclusion Criteria:

Infants are eligible if they meet all the following inclusion criteria except 4.

1. ≥36 weeks gestation
2. Either a 10-minute Apgar score ≤5, continued need for resuscitation for at least 10 minutes, or severe acidosis, defined as pH <7.0 or base deficit ≥16 mmol/L in a sample of umbilical cord blood or any blood during the first hour after birth
3. Moderate to severe encephalopathy (Sarnat II to III)
4. A moderately or severely abnormal background amplitude-integrated EEG (aEEG) voltage, or seizures identified by aEEG, if monitored
5. Up to 24 hours of age
6. A person with parental authority must have consented for the study.

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 growth restriction, with birth-weight less than 1800 g
4. Severe infectious disease, such as sepsis
5. Infants judged critically ill and unlikely to benefit from neonatal intensive care including hypothermia by the attending neonatologist

Study Plan

How is the study designed?

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Cell-treated; Infants with encephalopathy who receive autologous umbilical cord blood cell therapy along with therapeutic hypothermia.	Biological: Autologous cord blood cell therapy; The neonates receive their own non-cryopreserved volume- and red blood cell-reduced cord blood cells. The cord blood cells are divided into 3 doses and intravenously infused at 12-24, 36-48, and 60-72 hours after the birth.
Cooled only; Infants with encephalopathy who receive therapeutic hypothermia only.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Changes in serum levels of cytokines and trophic factors	From birth up to 10 days of age

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Association with neuroimaging and neurodevelopmental functional outcome	Neuroimaging at 12 months of age and neurodevelopmental function at 18 months of age will be assessed whether they are associated with serum levels of cytokines and trophic factors during the early neonatal period.	18 months

Collaborators and Investigators

• Sponsor: Neonatal Encephalopathy Consortium, Japan
• Collaborators: National Cerebral and Cardiovascular Center; Nagoya University; Tokyo Women's Medical University; Tokyo University; Osaka City University; Saitama Medical University; Kurashiki Central Hospital; Osaka City General Hospital; Yodogawa Christian Hospital; National Center for Child Health and Development, Japan
• Investigators: Study Director: Haruo Shintaku, MD, PhD, Osaka City University Graduate School of Medicine

Study record dates

Study Major Dates

• Study Start: April 1, 2015
• Primary Completion (ANTICIPATED): March 1, 2020
• Study Completion (ANTICIPATED): September 1, 2020

Study Registration Dates

• First Submitted: May 26, 2015
• First Submitted That Met QC Criteria: May 26, 2015
• First Posted (ESTIMATE): May 28, 2015

Study Record Updates

• Last Update Posted (ACTUAL): October 29, 2019
• Last Update Submitted That Met QC Criteria: October 28, 2019
• Last Verified: October 1, 2019

More Information

Terms related to this study

• Keywords: Cytokines; Neonatal encephalopathy; Hypoxic-ischemic encephalopathy; Newborn infants; Trophic factors
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Central Nervous System Diseases; Nervous System Diseases; Signs and Symptoms, Respiratory; Hypoxia; Hypoxia, Brain; Brain Ischemia; Brain Diseases; Hypoxia-Ischemia, Brain
• Other Study ID Numbers: UMIN000014903-Cytokines