NCT02621944 · University of Florida
Melatonin as a Neuroprotective Therapy in Neonates With HIE Undergoing Hypothermia
What this study is about
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.
View original scientific description
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.
Interventions
DRUG
Melatonin
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.
OTHER
Magnetic Resonance Imaging
All participants will receive an MRI between 7-12 days of age.
OTHER
Pharmacokinetics
All participants will receive pharmacokinetics to test the amount of melatonin in the blood.
BEHAVIORAL
Neurological Outcome Assessment
All participants will receive the Bayley-III Scores and Subsets for neurological outcome assessments.
Primary outcome measures
To identify the maximum tolerated dose of Melatonin
Time frame: Changes in Baseline to day 3
The maximum tolerated dose (MTD) is defined as the highest dose level without adverse events in no more than 1 out of 6 patients
Bayley-III Index Scores (Cognitive, Language, and Motor) will be used for neurological outcome assessment
Time frame: Approximately 18 - 20 Months
All raw scores will be transformed into norm-referenced standard scores (scale mean = 100 with s.d. = 15) using the Bayley-III scoring software published with the test. To dichotomize "good" and "poor" outcomes for statistical analysis, standardized scores that are at or greater than one standard deviation below the normative sample mean published with the test (i.e., standard scores \< 85) will be classified as "poor outcome" while higher scores will be classified as "good outcome".
Peak Plasma Concentration (Cmax) of Melatonin 0.5 mg/kg.
Time frame: 0 (baseline), 3, 5, 6, 12, 24, 48, 96 hours and day 14 (one sample)
HPLC-ESI/MS/MS will be used to measure melatonin concentrations in the serum samples. The two-way ANOVA (treatments are dose level and timepoint) framework for testing. Testing will be done using a likelihood ratio test, either using large-sample theory approximation or using bootstrap.
Number of participants with treatment-related adverse events as assessed by MedDRA ??? This is something the PI/Team needs to agree on which one to use.
Time frame: Baseline ongoing to Day 14
Incidence/Grade of Treatment Emergent Adverse Events (TEAEs), Serious Adverse Events (SAEs), laboratory abnormalities Percentage and number of subjects who discontinued for adverse event
Peak Plasma Concentration (Cmax) of Melatonin 3 mg/kg.
Time frame: 0 (baseline), 3, 5, 6, 12, 24, 48, 96 hours and day 14 (one sample)
HPLC-ESI/MS/MS will be used to measure melatonin concentrations in the serum. The two-way ANOVA (treatments are dose level and timepoint) framework for testing. Testing will be done using a likelihood ratio test, either using large-sample theory approximation or using bootstrap.
Peak Plasma Concentration (Cmax) of Melatonin 5 mg/kg.
Time frame: 0 (baseline), 3, 5, 6, 12, 24, 48, 96 hours and day 14 (one sample)
HPLC-ESI/MS/MS will be used to measure melatonin concentrations in the serum samples. The two-way ANOVA (treatments are dose level and timepoint) framework for testing. Testing will be done using a likelihood ratio test, either using large-sample theory approximation or using bootstrap.
Who can participate
This study lists these criteria on ClinicalTrials.gov. A study coordinator reviews eligibility during screening — this page does not determine whether you qualify.
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.
Where
- Gainesville, Florida
- Orlando, Florida
Collaborators
Thrasher Research Fund
Related conditions & keywords
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Data: ClinicalTrials.gov · synced Jun 29, 2026 · Source of record for eligibility and locations