Use of Melatonin for Neuroprotection in Asphyxiated Newborns (MELPRO)

University Hospital of Ferrara

Status: Unknown

Conditions: Asphyxia Perinatal; Cell Damage; Hypoxic-Ischemic Encephalopathy

Treatments: Other: PLACEBO group; Dietary Supplement: Melatonin

Study type: Interventional

Funder types: Other

Identifiers

NCT03806816

23/2018/SPER/AOUFE

Details and patient eligibility

About

Protection of brain development is a major aim in the Neonatal Intensive Care Unit. Hypoxic-Ischemic Encephalopathy (HIE) occurs in 3-5 per 1000 births. Only 47% of neonates have normal outcomes. The neurodevelopmental consequences of brain injury for asphyxiated term infants include cerebral palsy, severe intellectual disabilities and also a number of minor behavioural and cognitive deficits. However, there are very few therapeutic strategies for the prevention or treatment of brain damage. The gold standard is hypothermic treatment but, according to the literature, melatonin potentially acts in synergy with hypothermia for neuroprotection and to improve neurologic outcomes. Melatonin appears to be a good candidate because of its different protective effects including reactive oxygen species scavenging, excitotoxic cascade blockade, modulation of neuroinflammatory pathways.

The research study will evaluate the neuroprotective properties and the effects of Melatonin in association with therapeutic hypothermia for hypoxic ischemic encephalopathy.

Full description

It is a randomized double blind, placebo controlled trial on 100 neonates with moderate to moderately to severe hypoxic ischemic encephalopathy (HIE) . HIE infants are randomized into two groups: Whole body cooling group (N = 50 receive 72 hours of whole body hypothermia) and melatonin/ hypothermia group (N = 50; receive hypothermia and 5 daily enteral doses of melatonin 10 mg/kg). Serum melatonin and autophagy levels are measured at enrollment, daily during the hypothermic treatment, at day 5 and 7 for the two HIE groups.

aEEG will be performed for 72 hrs during the hypothermic treatment and the re-warming. MRI and Spectroscopy analysis will be performed between day 5 and 7 of. After hospital discharge the infants will enter a follow-up program consisting in periodic clinical and developmental assessments until 2 years of age corrected for prematurity. An expert psychologist and a neonatologist will assess neurodevelopmental outcome using the Bayley Scales III at 6-12-24 months of corrected age.

Enrollment: 100 estimated patients

Sex: All

Ages: 1 to 6 hours old

Volunteers: No Healthy Volunteers

Inclusion criteria

• gestational age > 35 weeks and weight > 1800 gr
• Apgar score < 5 at 10 minutes o need for cardiopulmonary resuscitation at 10 minutes or evidence of base excess > 12 mmol/L or pH < 7,0 at initial blood gas analyses
• evidence of moderate or severa encephalopathy graded according to Sarnat&Sarnat neurological evaluation
• abnormal amplitude integrated electroencephalography

Exclusion criteria

• suspected inborn errors of metabolism
• major chromosomal congenital defects

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Single Blind

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100 participants in 2 patient groups

HYPOTHERMIA / MELATONIN group

Experimental group

Description:

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

Treatment:

Dietary Supplement: Melatonin

HYPOTHERMIA / PLACEBO group

Experimental group

Description:

HIE infants who will not receive melatonin in addition to the routine cooling treatment

Treatment:

Other: PLACEBO group