Melatonin as a Neuroprotective Therapy in Neonates With HIE Undergoing Hypothermia

Status:	Recruiting
Conditions:	Hospital, Neurology
Therapuetic Areas:	Neurology, Other
Healthy:	No
Age Range:	Any
Updated:	2/28/2019
Start Date:	November 2016
End Date:	January 2022
Contact:	Livia Sura, MPH, CPH
Email:	livia.sura@peds.ufl.edu
Phone:	3522738706

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.

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 determine the effect of melatonin on the inflammatory cascade, oxidative stress,
free radical production, and serum biomarkers of brain injury in neonates undergoing
hypothermia.

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 Criteria:

- suspected inborn errors of metabolism (elevated ammonia) and hypoglycemia,

- clinical signs and symptoms consistent with meningitis detected upon sepsis
evaluation,

- a diagnosis of congenital abdominal surgical problems along with multiple congenital
anomalies and/or chromosomal abnormalities.

We found this trial at

sites

University of Florida

Gainesville, Florida 32610

(352) 392-3261