NCT02621944

Melatonin as a Neuroprotective Therapy in Neonates With HIE Undergoing Hypothermia

• Status: Recruiting
• Phase: EARLY_Phase 1
• Study type: Interventional
• Enrollment: 70 (estimated)
• Sponsor: University of Florida · Academic / Other
• Sex: All
• Age: 6 Hours
• Healthy volunteers: Not accepted

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.

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

Conditions

• Hypoxic Ischemic Encephalopathy

Interventions

Type	Name	Description
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.

Timeline

• Start date: 2016-11-01
• Primary completion: 2026-03-01
• Completion: 2026-03-01
• First posted: 2015-12-04
• Last updated: 2025-10-02

Locations

2 sites across 1 country: United States

Regulatory

• FDA-regulated drug study