Erythropoietin in Infants With Hypoxic Ischemic Encephalopathy (HIE)
Primary Purpose
Hypoxic Ischemic Encephalopathy
Status
Completed
Phase
Phase 1
Locations
Egypt
Study Type
Interventional
Intervention
Human recombinant erythropoietin
EEG and Brain MRI
Nitric oxide measurement in the blood
Sponsored by
About this trial
This is an interventional treatment trial for Hypoxic Ischemic Encephalopathy focused on measuring Asphyxia neonatorum, Infants, EEG, Brain MRI, Nitric oxide
Eligibility Criteria
Inclusion Criteria:
- Inborn infants at term gestation (38-42 weeks)
- Apgar score ≤ 3 at 5 minutes and/or delayed first breath beyond five minutes after birth
- Profound metabolic or mixed acidosis with serum bicarbonate <12 mMol/L in initial arterial blood gas
- Evidence of encephalopathy such as stupor, coma, seizures, or hypotonia in the immediate neonatal period
Exclusion Criteria:
- Twin gestation
- Maternal diabetes
- Congenital malformations of the central nervous system
- Chromosomal abnormalities
- Chorioamnionitis and congenital infections
- Intrauterine growth restriction
Sites / Locations
- Tanta University Faculty of Medicine
Arms of the Study
Arm 1
Arm 2
Arm 3
Arm Type
Experimental
No Intervention
Other
Arm Label
EPO HIE Group
Control HIE
Healthy Controls
Arm Description
Infants with hypoxic ischemic encephalopathy receive human recombinant erythropoietin
Infants with hypoxic ischemic encephalopathy who do not receive treatment drug (EPO)
Healthy newborn without hypoxic ischemic encephalopathy
Outcomes
Primary Outcome Measures
Neurodevelopmental outcomes
EEG changes
MRI of the brain
Secondary Outcome Measures
Nitric oxide concentrations in the plasma
Full Information
1. Study Identification
Unique Protocol Identification Number
NCT00945789
Brief Title
Erythropoietin in Infants With Hypoxic Ischemic Encephalopathy (HIE)
Official Title
Human Recombinant Erythropoietin (HrEPO) in Asphyxia Neonatorum: A Pilot Trial
Study Type
Interventional
2. Study Status
Record Verification Date
September 2009
Overall Recruitment Status
Completed
Study Start Date
October 2007 (undefined)
Primary Completion Date
December 2008 (Actual)
Study Completion Date
June 2009 (Actual)
3. Sponsor/Collaborators
Name of the Sponsor
Tanta University
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
Brief Summary
In this prospective trial the investigators plan to study the efficacy of erythropoietin as a therapeutic agent in neonates who suffer from brain injury following perinatal asphyxia.
Detailed Description
During HIE free radicals are generated within mitochondria and also as byproducts in the synthesis of prostaglandins.These free radicals ignite a secondary phase of subsequent damage to the brain by attacking membranal fatty acids. Nitric oxide (NO) is involved in the cascade of metabolic events that contributes to HIE. It mediates, in part, the cytotoxic activity of macrophages, induces relaxation of blood vessels, and also acts as a neurotransmitter in the central and peripheral nervous system. Therefore, the therapeutic value of NO synthase inhibitors, among many other agents used to ameliorate the course of HIE, is currently under investigation in experimental animals.
Erythropoietin (EPO) is a cytokine originally identified for its role in erythropoiesis and more recently shown to be produced in the central nervous system.Relative insufficiency of endogenous EPO during periods of ischemic stress may trigger neuronal apoptosis, whereas the provision of exogenous EPO has been shown to inhibit this process. The potential immediate protective effects of EPO include decreased NO production, activation of antioxidant enzymes, reduction of glutamate toxicity, inhibition of lipid peroxidation, and reduction of inflammation. Long-term protective effects of EPO include the generation of neuronal anti-apoptotic mechanisms, stimulation of angiogenesis, and modulation of neurogenesis.
Preliminary data supports a protective role of exogenous EPO to neuronal cells. The presence of EPO rescues in vitro cultured neurons from NO-induced death. It specifically protects cultured neurons from N-methyl-D-aspartate (NMDA) receptor-mediated glutamate toxicity. Intercerebroventricular injection of EPO offered significant protection of neuronal tissue in animals with focal cerebral ischemia. EPO is able to cross the blood brain barrier, and its concentration in the cerebrospinal fluid in normal rats significantly increases within 30 minutes following intravenous administration. EPO also offered neuronal protection when it was administered systemically to animals suffering from global and focal cerebral ischemia. In adult patients with stroke, the administration of EPO ameliorates the course of the disease. Therefore, EPO has recently received much attention and is speculated to have a role in the protection of HIE infants. However, despite the biological plausibility and the encouraging preliminary data from animals and adult humans, surprisingly EPO has never been tried in newborns with HIE even though it has already been used in neonates for other indications and is known to be safe.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypoxic Ischemic Encephalopathy
Keywords
Asphyxia neonatorum, Infants, EEG, Brain MRI, Nitric oxide
7. Study Design
Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantInvestigatorOutcomes Assessor
Allocation
Non-Randomized
Enrollment
45 (Actual)
8. Arms, Groups, and Interventions
Arm Title
EPO HIE Group
Arm Type
Experimental
Arm Description
Infants with hypoxic ischemic encephalopathy receive human recombinant erythropoietin
Arm Title
Control HIE
Arm Type
No Intervention
Arm Description
Infants with hypoxic ischemic encephalopathy who do not receive treatment drug (EPO)
Arm Title
Healthy Controls
Arm Type
Other
Arm Description
Healthy newborn without hypoxic ischemic encephalopathy
Intervention Type
Drug
Intervention Name(s)
Human recombinant erythropoietin
Intervention Description
Epo dse is 2500 IU/kg subcutaneous daily for 5 days.
Intervention Type
Procedure
Intervention Name(s)
EEG and Brain MRI
Intervention Description
EEG to be done twice in hte first 48 hours and at 2-3 weeks. MRI to be done at 3 weeks of age.
Intervention Type
Biological
Intervention Name(s)
Nitric oxide measurement in the blood
Intervention Description
Concentration of nitric oxide is measured in the blood at enrollment. For the 2 groups with asphyxia, measurement to be repeated in 2 weeks.
Primary Outcome Measure Information:
Title
Neurodevelopmental outcomes
Time Frame
6 months
Title
EEG changes
Time Frame
2-3 weeks
Title
MRI of the brain
Time Frame
3 weeks
Secondary Outcome Measure Information:
Title
Nitric oxide concentrations in the plasma
Time Frame
2 weeks
10. Eligibility
Sex
All
Maximum Age & Unit of Time
24 Hours
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria:
Inborn infants at term gestation (38-42 weeks)
Apgar score ≤ 3 at 5 minutes and/or delayed first breath beyond five minutes after birth
Profound metabolic or mixed acidosis with serum bicarbonate <12 mMol/L in initial arterial blood gas
Evidence of encephalopathy such as stupor, coma, seizures, or hypotonia in the immediate neonatal period
Exclusion Criteria:
Twin gestation
Maternal diabetes
Congenital malformations of the central nervous system
Chromosomal abnormalities
Chorioamnionitis and congenital infections
Intrauterine growth restriction
Facility Information:
Facility Name
Tanta University Faculty of Medicine
City
Tanta
Country
Egypt
12. IPD Sharing Statement
Citations:
PubMed Identifier
20385632
Citation
Elmahdy H, El-Mashad AR, El-Bahrawy H, El-Gohary T, El-Barbary A, Aly H. Human recombinant erythropoietin in asphyxia neonatorum: pilot trial. Pediatrics. 2010 May;125(5):e1135-42. doi: 10.1542/peds.2009-2268. Epub 2010 Apr 12.
Results Reference
derived
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Erythropoietin in Infants With Hypoxic Ischemic Encephalopathy (HIE)
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