Melatonin for Neuroprotection Following Perinatal Asphyxia

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.

Study Overview

• Status: Completed
• Conditions: Perinatal Asphyxia
• Intervention / Treatment: Drug: Melatonin

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.

• Study Type: Interventional
• Enrollment (Actual): 45
• Phase: Phase 2; Phase 1

Contacts and Locations

Study Locations

• Egypt
  • Gharbeya
    • Tanta, Gharbeya, Egypt
      • Tanta University Children's Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: No older than 3 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
No Intervention: Healthy Control; 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; HIE infants who will not receive melatonin and only receive routine cooling protocol.
Experimental: Melatonin/ hypothermia group; HIE infants who will receive melatonin in addition to the routine cooling protocol	Drug: Melatonin; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	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	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

Collaborators and Investigators

• Sponsor: Tanta University
• Investigators: Principal Investigator: Heba Mahdy, MD, Tanta University

Publications and helpful links

General Publications

• 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.
• 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.
• 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.

Study record dates

Study Major Dates

• Study Start: January 1, 2012
• Primary Completion (Actual): December 1, 2013
• Study Completion (Actual): December 1, 2013

Study Registration Dates

• First Submitted: February 23, 2014
• First Submitted That Met QC Criteria: February 23, 2014
• First Posted (Estimate): February 25, 2014

Study Record Updates

• Last Update Posted (Estimate): February 25, 2014
• Last Update Submitted That Met QC Criteria: February 23, 2014
• Last Verified: February 1, 2014

More Information

Terms related to this study

• Keywords: MRI; HIE; hypothermia; encephalopathy; anti oxidants
• Additional Relevant MeSH Terms: Pathologic Processes; Wounds and Injuries; Infant, Newborn, Diseases; Death; Asphyxia; Asphyxia Neonatorum; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Protective Agents; Antioxidants; Melatonin
• Other Study ID Numbers: 01012012