Melatonin for Neuroprotection Following Perinatal Asphyxia

NCT ID: NCT02071160

Last Updated: 2014-02-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE1/PHASE2
• Total Enrollment: 45 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2012-01-31
• Study Completion Date: 2013-12-31

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.

Conditions

Perinatal Asphyxia

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

Healthy Control

A group of healthy control without any history suggestive of perinatal asphyxia or other diseases, are enrolled to compare different laboratory measurements

Group Type: NO_INTERVENTION

No interventions assigned to this group

Hypothermia Group

HIE infants who will not receive melatonin and only receive routine cooling protocol.

Group Type: NO_INTERVENTION

No interventions assigned to this group

Melatonin/ hypothermia group

HIE infants who will receive melatonin in addition to the routine cooling protocol

Group Type: EXPERIMENTAL

Melatonin

Intervention Type: DRUG

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.

Interventions

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.

Intervention Type: DRUG

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.

• Maximum Eligible Age: 6 Hours
• Eligible Sex: ALL
• Accepts Healthy Volunteers: Yes

Sponsors

Tanta University

OTHER

Sponsor Role: lead

Responsible Party

Heba Mahdy

Assistant Professor of Pediatrics

Responsibility Role: PRINCIPAL_INVESTIGATOR

Principal Investigators

Heba Mahdy, MD

Role: PRINCIPAL_INVESTIGATOR

Tanta University

Locations

Tanta University Children's Hospital

Tanta, Gharbia Governorate, Egypt

Countries

Egypt

References

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.

Reference Type: BACKGROUND

PMID: 15168319 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 14966737 (View on PubMed)

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.

Reference Type: BACKGROUND

PMID: 22370283 (View on PubMed)

Other Identifiers

01012012

Identifier Type: -

Identifier Source: org_study_id