Melatonin as a Neuroprotective Therapy in Neonates With HIE Undergoing Hypothermia
University of Florida
Summary
Hypoxic-Ischemic Encephalopathy (HIE) occurs in 20 per 1000 births. Only 47% of neonates treated with the state of the art therapy (induced systemic hypothermia) have normal outcomes. Therefore, other promising therapies that potentially work in synergy with hypothermia to improve neurologic outcomes need to be tested. One potential agent is melatonin. Melatonin is a naturally occurring substance produced mainly from the pineal gland. Melatonin is widely known for its role in regulating the circadian rhythm, but it has many other effects that may benefit infants with HI injury. Melatonin serves as a free radical scavenger, decreases inflammatory cytokines, and stimulates anti-oxidant enzymes. Therefore, melatonin may interrupt several key components in the pathophysiology of HIE, in turn minimizing cell death and improving outcomes. The research study will evaluate the neuroprotective properties and appropriate dose of Melatonin to give to infants undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy.
Description
Thirty subjects will be enrolled in a dose escalation study. Subjects 1-10 will receive melatonin (0.5 mg/kg). If that dose proves to be safe, subjects 11-20 will receive an increased dose of melatonin (3 mg/kg). Subjects 21-30 will receive a dose increased to the targeted projected therapeutic dose (5 mg/kg). The serum concentration of melatonin and capture adverse event reports during this dose escalation study in neonates undergoing hypothermia and the long-term safety and potential efficacy via developmental follow-up performed at 18-22 months of age. In addition, this study will determin…
Eligibility
- Age range
- Up to 6 years
- Sex
- All
- Healthy volunteers
- No
Inclusion Criteria: * Eligible infants are \>36 0/7th weeks gestation, * pH (cord or neonatal) \<7.0, * base deficit \>16 mEq/L, * no available blood gas, * a cord blood/first hour of life blood gas with pH \> 7.0 and \< 7.15, * base deficit between 10 and 15.9 mEq/L, * infants must have a history of an acute perinatal event, * either a 10-minute Apgar \< 5 or a continued need for ventilation, * All infants must have signs of encephalopathy within 6 hours of age using the modified Sarnat scoring system, * neonates cooled within 6 hours of birth will be included in the study. Exclusion Criter…
Interventions
- DrugMelatonin
Participants 1-10 will receive a 0.5 mg/kg enteral dose of Melatonin. Participants 11-20 will receive Melatonin dose of 3 mg/kg enteral. Participants 21-30 will receive Melatonin dose of 5 mg/kg enterally.
- OtherMagnetic Resonance Imaging
All participants will receive an MRI between 7-12 days of age.
- OtherPharmacokinetics
All participants will receive pharmacokinetics to test the amount of melatonin in the blood.
- BehavioralNeurological Outcome Assessment
All participants will receive the Bayley-III Scores and Subsets for neurological outcome assessments.
Locations (2)
- University of FloridaGainesville, Florida
- Florida Hospital for ChildrenOrlando, Florida