Melatonin for Neuroprotection Following Perinatal Asphyxia

Perinatal Asphyxia Clinical Trial

Official title:

Melatonin for Neuroprotection Following Perinatal Asphyxia

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02071160
• Other study ID #: 01012012
• Status: Completed
• Phase: Phase 1/Phase 2
• First received: February 23, 2014
• Last updated: February 23, 2014
• Start date: January 2012
• Est. completion date: December 2013

Study information

• Verified date: February 2014
• Source: Tanta University
• Contact: n/a
• Is FDA regulated: No
• Health authority: Egypt: Ministry of Higher Education
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 45
• Est. completion date: December 2013
• Est. primary completion date: December 2013
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: N/A to 6 Hours

Eligibility

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 Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Treatment

Related Conditions & MeSH terms

• Asphyxia
• Asphyxia Neonatorum
• Perinatal Asphyxia

Intervention

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.

Locations

Country	Name	City	State
Egypt	Tanta University Children's Hospital	Tanta	Gharbeya

Sponsors (1)

Lead Sponsor	Collaborator
Tanta University

Country where clinical trial is conducted

Egypt, 

References & Publications (3)

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. Review. — View Citation

Gitto E, Reiter RJ, Cordaro SP, La Rosa M, Chiurazzi P, Trimarchi G, Gitto P, Calabrò 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. — View 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. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Serum melatonin concentration (pg/ ml)		5 days	No
Primary	Plasma superoxide dismutase (SOD) activity (U/ml)		5 days	No
Primary	Serum nitric oxide (NO) concentrations (µmol/L)		5 days	No
Secondary	Incidence of EEG abnormalities		2 weeks	No
Secondary	Incidence of MRI abnormalities		2 weeks	No
Secondary	Incidence of abnormal neurological examination		6 months	No
Secondary	Incidence of abnormal Denver Developmental Screening Test II		6 months	No