Severe Hypoxic-ischemic Encephalopathy
Conditions
Keywords
Neonates, hypoxic-ischemic encephalopathy, human placental-derived stem cells, autologous
Brief summary
The purpose of this study is to investigate the safety and effectiveness of autologous human placental-derived stem cells (HPDSC) in combination with autologous cord blood in neonates with severe hypoxic-ischemic encephalopathy.
Detailed description
The primary aim of this study is to determine the safety, tolerability and feasibility of intravenous administration of autologous cord blood (CB) and autologous human placental derived stem cells (HPDSC) in neonates with severe hypoxic-ischemic encephalopathy (HIE). It is hypothesized that the administration of autologous CB and autologous HPDSC will be safe and well tolerated in neonates with severe HIE. Additionally, postnatal neuro-developmental outcomes in neonates with HIE after autologous CB and HPDSC therapy will be measured; HIE injury to the neonate/infant brain post autologous CB and HPDSC therapy by imaging will be characterized; the pluripotent stem cell properties of CB and HPDSC will be characterized; serum levels of selected circulating cytokine and neurotrophic factors in neonates with HIE before and after autologous CB and HPDSC therapy will be compared and immune cell phenotype and function in neonates with HIE before and after autologous CB and HPDSC therapy will be compared.
Interventions
DRUGHPDSC
Autologous HPDSC collected after birth will be infused in aliquots. one-half of the HPDSC infused on Day 2; one-half of the collected HPDSC will be infused on Day 8.
DRUGCord blood
Autologous Cord Blood collected after birth will be infused in aliquots. One-third of the collected cord blood will be infused within the first 24 hours after birth (Day 0); one-third of the collected cord blood will be infused on day 3; and one-third of the collected cord blood unit will be infused on Day 7.
Sponsors
Celgene
New York Medical College
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
1 Minutes to 6 Hours
Healthy volunteers
No
Inclusion criteria
* Gestational age ≥ 36 weeks * Birth weight ≥ 1800 grams * Postnatal age after birth of less than 6 hours * Autologous cord blood and HPDSCs available for infusion * Plus one or more of the following criteria: Apgar ≤ 5 at 10 minutes of postnatal age, or Continued need for resuscitation ≥10 min after birth, or Acidosis-cord blood pH or arterial blood pH within 60 minutes of birth ≤ 7.0 pH, or Base deficit ≥ minus 16mEq in cord blood and within 60 min of birth. * Plus Moderate to Severe Altered State of Consciousness, by one or more of the following: Hypotonia, or Abnormal reflexes, or Absent/weak suck.
Exclusion criteria
* Major life-threatening or surgical anomalies * Polycythemia (hematocrit \> 65%) * Congenital infection based on antenatal diagnosis of TORCH infection * Parental refusal for study * Infant expected to live \< 24h, medical care is considered futile and no additional therapy will be offered by the attending neonatologist
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Number of subjects with infusion reaction as a measure of safety and tolerability | within the first 30 days | Any infusion reaction to autologous human placental-derived stem cells (HPDSC) administered in conjunction autologous cord blood in neonates with severe hypoxic-ischemic encephalopathy will be assessed for safety and tolerability |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Improvement in neurological condition | 2 years post HPDSC infusion | Improvement in neurological condition as shown on head MRI, DTI and neurological development by Sarnat testing. |
Countries
United States
Outcome results
None listed