Clinical trial NCT02071160: Melatonin for Neuroprotection Following Perinatal Asphyxia
Official title: Melatonin for Neuroprotection Following Perinatal Asphyxia
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Perinatal Asphyxia
Keywords: HIE
hypothermia
encephalopathy
anti oxidants
MRI
Lead sponsor: Tanta University
Sponsor class: OTHER
First posted: 2014-02-25
Enrollment: 45
Sex: ALL
Maximum age (years): 6
Standard ages: CHILD
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Serum melatonin concentration (pg/ ml)
timeFrame: 5 days
measure: Plasma superoxide dismutase (SOD) activity (U/ml)
timeFrame: 5 days
measure: Serum nitric oxide (NO) concentrations (µmol/L)
timeFrame: 5 days
Secondary outcomes:
measure: Incidence of EEG abnormalities
timeFrame: 2 weeks
measure: Incidence of MRI abnormalities
timeFrame: 2 weeks
measure: Incidence of abnormal neurological examination
timeFrame: 6 months
measure: Incidence of abnormal Denver Developmental Screening Test II
timeFrame: 6 months
Other outcomes:
Locations:
city: Tanta
country: Egypt
facility: Tanta University Children's Hospital
state: Gharbeya
Study officials:
affiliation: Tanta University
name: Heba Mahdy, MD
role: PRINCIPAL_INVESTIGATOR
References:
citation: Gitto E, Reiter RJ, Cordaro SP, La Rosa M, Chiurazzi P, Trimarchi G, Gitto P, Calabro MP, Barberi I. Oxidative and inflammatory parameters in respiratory distress syndrome of preterm newborns: beneficial effects of melatonin. Am J Perinatol. 2004 May;21(4):209-16. doi: 10.1055/s-2004-828610.
citation: Gitto E, Romeo C, Reiter RJ, Impellizzeri P, Pesce S, Basile M, Antonuccio P, Trimarchi G, Gentile C, Barberi I, Zuccarello B. Melatonin reduces oxidative stress in surgical neonates. J Pediatr Surg. 2004 Feb;39(2):184-9; discussion 184-9. doi: 10.1016/j.jpedsurg.2003.10.003.
citation: Chen YC, Tain YL, Sheen JM, Huang LT. Melatonin utility in neonates and children. J Formos Med Assoc. 2012 Feb;111(2):57-66. doi: 10.1016/j.jfma.2011.11.024. Epub 2012 Feb 15.