Use of Melatonin for Neuroprotection in Term Infants With Hypoxic-ischaemic Encephalopathy
试验速览
- 阶段
- 不适用
- 发起方
- 入组人数
- 100
- 试验地点
- 8
- 主要终点
- Bayley III scale
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Single (Outcomes Assessor)
入排标准
- 年龄范围
- 1 Hour 至 6 Hours（Child）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •suspected inborn errors of metabolism
- •major chromosomal congenital defects
研究组 & 干预措施
HYPOTHERMIA / PLACEBO group
HIE infants who will not receive melatonin in addition to the routine cooling treatment
干预措施: PLACEBO group (Other)
HYPOTHERMIA / MELATONIN group
HIE infants who will receive melatonin in addition to the routine cooling treatment
干预措施: Melatonin (Dietary Supplement)
结局指标
主要结局
Bayley III scale
时间窗: 12 months
Bayley scale of infant and toddler development. It measures developmental skills reached by infant and young children between 1 month and 42 months The scale is subdivided into 5 subscales Cognitive,Receptive communication,Expressive communication,Fine motor ,Gross motor.Receptive and expressive communication have a composite in language score So as fine and gross motor in motor score For all subtests raw scores correspond to scaled scores ranging from 1 to 19 with a mean of 10 and SD of 3 The composite scores are given by the sum of the corresponding subtests scaled scores. Two parent-reported scales (Social-Emotional and Adaptive Behavior) will be collected.
次要结局
- brain MRI(between the 5th and 7th days of life)
- continuous aEEG(Continuous monitoring for the first 72 hours and for the rewarmed)
- Plasma Concentration of Melatonin(at birth, 24 hours, 48 hours, 72 hours, 5 days, 7 days of life)
- ATG5 Plasma concentration(at birth, 24 hours, 48 hours, 72 hours, 5 days, 7 days of life)
研究者
Anna Tarocco
Medical Doctor, Principal Investigator
University Hospital of Ferrara