Melatonin for Neuroprotection Following Perinatal Asphyxia

Study Overview
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Brief Summary
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The aim of this study is to examine the effect of combining melatonin to whole body cooling on the brain injury and outcome of neonates following perinatal asphyxia.

Detailed Description
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This is a prospective study on 30 neonates with moderate to moderately to severe hypoxic ischemic encephalopathy (HIE) . HIE infants are randomized into two groups: Whole body cooling group (N = 15; receive 72 hours of whole body hypothermia) and melatonin/ hypothermia group (N = 15; receive hypothermia and 5 daily enteral doses of melatonin 10 mg/kg). Serum melatonin, plasma superoxide dismutase (SOD),and serum nitric oxide (NO) are measured at enrollment and after 2 weeks for the two HIE groups. The HIE groups underwent electroencephalography at enrollment and at 2 to 3 weeks. Brain MRI was performed after 2 weeks of life. Neurologic evaluations and Denver Developmental Screening Test II assessments were performed at 6 months. A group of healthy newborns will be used as a control for baseline labs.

Official Title
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Melatonin for Neuroprotection Following Perinatal Asphyxia

Conditions
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Perinatal Asphyxia

Intervention / Treatment
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* Drug: Melatonin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Inborn infants at term gestation (38-42 weeks) Apgar scores ≤ 3 at 5 minutes and/or delayed first breath (>5 minutes after birth) Profound metabolic or mixed acidosis with serum bicarbonate levels of <12 mmol/L in initial blood gas analyses Evidence of moderate or moderate to severe encephalopathy, such as lethargy, seizures, abnormal reflexes, or hypotonia, in the immediate neonatal period Exclusion Criteria: Twin gestation Maternal neuro-endocrinal disturbances including diabetes mellitus Chorioamnionitis or congenital infections Low birth weight less than 2.5 kg Congenital malformations of the central nervous system or gastrointestinal anomalies Chromosomal abnormalities After 6 hours of birth. Patients in extremis such as: (1) hypoxemia requiring supplemental oxygen 100% FiO2, (2) life threatening coagulopathy, or (3) deep coma.

Ages Eligible for Study
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Maximum Age: 6 Hours

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Healthy Control<br>A group of healthy control without any history suggestive of perinatal asphyxia or other diseases, are enrolled to compare different laboratory measurements | |
| No Intervention: Hypothermia Group<br>HIE infants who will not receive melatonin and only receive routine cooling protocol. | |
| Experimental: Melatonin/ hypothermia group<br>HIE infants who will receive melatonin in addition to the routine cooling protocol | Drug: Melatonin<br>* Melatonin is administered to the melatonin/hypothermia group (n=15) in a dose of 10 mg/kg daily for a total of 5 doses starting immediately at enrollment. Melatonin tablets (1 or 3 mg/tablet) (Puritan's Pride,Oakdale, NY, USA) are crushed, then dissolved in 5-10 ml of distilled water , then administered via an orogastric tube.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Serum melatonin concentration (pg/ ml) |  | 5 days | 
| Plasma superoxide dismutase (SOD) activity (U/ml) |  | 5 days | 
| Serum nitric oxide (NO) concentrations (µmol/L) |  | 5 days | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Incidence of EEG abnormalities |  | 2 weeks | 
| Incidence of MRI abnormalities |  | 2 weeks | 
| Incidence of abnormal neurological examination |  | 6 months | 
| Incidence of abnormal Denver Developmental Screening Test II |  | 6 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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MRI, HIE, hypothermia, encephalopathy, anti oxidants