Hypoxic Ischemic EncephalopathyPhase 1/2NCT00945789
Erythropoietin in Infants With Hypoxic Ischemic Encephalopathy (HIE)
A Phase 1/2 study testing Human recombinant erythropoietin, EEG and Brain MRI and Nitric oxide measurement in the blood in people with Hypoxic Ischemic Encephalopathy, run by Tanta University at 1 site in Egypt.
Trial 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. Read more about this study
- Who is it for?
- Ages Up to 24 hours
- Conditions the study is for
- Hypoxic Ischemic Encephalopathy
- What is being tested?
- Human recombinant erythropoietin, EEG and Brain MRI and Nitric oxide measurement in the blood
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 45 participants
- Where
- 1 siteEgypt
- Study dates
- Oct 2007to Jun 2009
- 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
- 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
Who cannot join
- Twin gestation
- Maternal diabetes
- Congenital malformations of the central nervous system
- Chromosomal abnormalities
- Chorioamnionitis and congenital infections
- Intrauterine growth restriction
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Human Recombinant Erythropoietin (HrEPO) in Asphyxia Neonatorum: A Pilot Trial
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.
Read the 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.
- Conditions
- Hypoxic Ischemic Encephalopathy
- Being tested
- Human recombinant erythropoietin, EEG and Brain MRI, Nitric oxide measurement in the blood
- Keywords
- Asphyxia neonatorum, Infants, EEG, Brain MRI, Nitric oxide
- Medical subject headings
- Hypoxia-Ischemia, Brain, Asphyxia Neonatorum
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Human recombinant erythropoietinDrug
Epo dse is 2500 IU/kg subcutaneous daily for 5 days.
EEG and Brain MRIProcedure or surgery
EEG to be done twice in hte first 48 hours and at 2-3 weeks. MRI to be done at 3 weeks of age.
Nitric oxide measurement in the bloodBiological
Concentration of nitric oxide is measured in the blood at enrollment. For the 2 groups with asphyxia, measurement to be repeated in 2 weeks.
| Study group | Role | What they receive |
|---|---|---|
| EPO HIE Group | Experimental | Infants with hypoxic ischemic encephalopathy receive human recombinant erythropoietin Receives: Drug: Human recombinant erythropoietin; Procedure: EEG and Brain MRI; Biological: Nitric oxide measurement in the blood |
| Control HIE | No intervention | Infants with hypoxic ischemic encephalopathy who do not receive treatment drug (EPO) Receives: Procedure: EEG and Brain MRI; Biological: Nitric oxide measurement in the blood |
| Healthy Controls | Other | Healthy newborn without hypoxic ischemic encephalopathy Receives: Biological: Nitric oxide measurement in the blood |
What is being measured
The primary outcome is the main question the study is designed to answer.
Neurodevelopmental outcomes
Measured: 6 months
EEG changes
Measured: 2-3 weeks
MRI of the brain
Measured: 3 weeks
Secondary outcomes (1)
Nitric oxide concentrations in the plasma
Measured: 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2009 (estimated)
- Study startOct 2007
- Primary completionDec 2008
- Study completionJun 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Hypoxic Ischemic EncephalopathyStudies of the same condition, open and under way.
- More trials run by Tanta UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
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
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Investigator, Outcomes assessor
- Enrolment
- 45 participants (actual)
Sponsor and investigators
- Lead sponsor
- Tanta University
- Sponsor type
- University, hospital or other
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00945789
- Sponsor's protocol ID
- 1102007
- Status last verified
- Sep 2009
- First submitted
- 23 Jul 2009
- Last updated
- 28 Sep 2009
- Results posted
- No
- Data monitoring committee
- Yes
Publications
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.
PubMed 20385632
Study at a glance
From the registry record, last updated by the sponsor on 28 Sep 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Human Recombinant Erythropoietin (HrEPO) in Asphyxia Neonatorum: A Pilot Trial
- ClinicalTrials.gov ID
- NCT00945789
- Acronym / sponsor ID
- 1102007
- Conditions
- Hypoxic Ischemic Encephalopathy
- Keywords
- Asphyxia neonatorum, Infants, EEG, Brain MRI, Nitric oxide
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 45 participants (actual)
- Lead sponsor
- Tanta UniversityUniversity, hospital or other
- Study start
- Oct 2007
- Primary completion
- Dec 2008 (actual)
- Study completion
- Jun 2009 (actual)
- First posted
- 24 Jul 2009 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Non-randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, investigator, outcomes assessor)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| EPO HIE Group | Experimental | Drug: Human recombinant erythropoietin, Procedure: EEG and Brain MRI, Biological: Nitric oxide measurement in the bloodInfants with hypoxic ischemic encephalopathy receive human recombinant erythropoietin |
| Control HIE | No intervention | Procedure: EEG and Brain MRI, Biological: Nitric oxide measurement in the bloodInfants with hypoxic ischemic encephalopathy who do not receive treatment drug (EPO) |
| Healthy Controls | Other | Biological: Nitric oxide measurement in the bloodHealthy newborn without hypoxic ischemic encephalopathy |
Who may qualify
- Ages
- Up to 24 hours
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child
Key inclusion criteria (4 listed)
- 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
Key exclusion criteria (6 listed)
- Twin gestation
- Maternal diabetes
- Congenital malformations of the central nervous system
- Chromosomal abnormalities
- Chorioamnionitis and congenital infections
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Human recombinant erythropoietinEpo dse is 2500 IU/kg subcutaneous daily for 5 days. | Drug | EPO HIE Group |
| EEG and Brain MRIEEG to be done twice in hte first 48 hours and at 2-3 weeks. MRI to be done at 3 weeks of age. | Procedure or surgery | Control HIE, EPO HIE Group |
| Nitric oxide measurement in the bloodConcentration of nitric oxide is measured in the blood at enrollment. For the 2 groups with asphyxia, measurement to be repeated in 2 weeks. | Biological | Control HIE, EPO HIE Group, Healthy Controls |
Primary outcome
Neurodevelopmental outcomes
Time frame: 6 months
EEG changes
Time frame: 2-3 weeks
MRI of the brain
Time frame: 3 weeks
1 secondary outcome
Nitric oxide concentrations in the plasma
Time frame: 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Sep 2009.
- Derived from this study: PubMed 20385632Elmahdy 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.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing Human recombinant erythropoietin, EEG and Brain MRI and Nitric oxide measurement in the blood in people with Hypoxic Ischemic Encephalopathy, run by Tanta University at 1 site in Egypt.
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 4 inclusion and 6 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: finished, as of the sponsor's last update on 28 Sep 2009. 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 Egypt. 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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
Neurodevelopmental outcomes (time frame: 6 months). The study lists 3 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 NCT00945789, which also lists 1 linked publication.
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 28 Sep 2009.