Melatonin as a Neuroprotective Therapy in Neonates With HIE Undergoing Hypothermia

Conditions

• Hypoxic Ischemic Encephalopathy

Eligibility Criteria

Sex

ALL

Age

N/A - 6 Hours

Healthy Volunteers

Not accepted

Interventions

• Melatonin — DRUG
  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.
• Magnetic Resonance Imaging — OTHER
  All participants will receive an MRI between 7-12 days of age.
• Pharmacokinetics — OTHER
  All participants will receive pharmacokinetics to test the amount of melatonin in the blood.
• Neurological Outcome Assessment — BEHAVIORAL
  All participants will receive the Bayley-III Scores and Subsets for neurological outcome assessments.

Study Details

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.

Key Dates

Start date

Nov 30, 2016

Status verified

Sep 2025

Primary completion

Mar 31, 2026

Completion

Mar 31, 2026

Study Design

Enrollment

70 participants (estimated)

Allocation

NON_RANDOMIZED

Intervention model

SINGLE_GROUP

Primary purpose

TREATMENT

Arms

• Experimental: Participants 1-10
  This group will receive a 0.5 mg/kg enteral dose of Melatonin. The first dose will be administered via enteral route within 12 hours of life with a target of 6 hours of life. The melatonin will be administered as a single dose for the first 5 participants in allowing the investigators to determine if the dosing frequency has the potential to decrease in the elimination with hypothermia. The next 5 subjects who will receive multiple doses if there are not any safety concerns. Additionally, the participants will have the following test performed: Magnetic Resonance Imaging (MRI), Neurological Outcome Assessment, Pharmacokinetics, and safety monitoring.
• Experimental: Participants 11-20
  This group will the Melatonin dose of 3 mg/kg enteral, only if the group Participants 1-10 has meet the safety goals. The first dose will be administered via enteral route within 12 hours of life with a target of 6 hours of life. The melatonin will be administered as a single dose for the first 5 participants in allowing the investigators to determine if the dosing frequency has the potential to decrease in the elimination with hypothermia. The next 5 subjects who will receive multiple doses if there are not any safety concerns. Additionally, the participants will have the following test performed: Magnetic Resonance Imaging (MRI), Neurological Outcome Assessment, Pharmacokinetics, and safety monitoring.
• Experimental: Participants 21-30
  This group will receive Melatonin dose of 5 mg/kg enterally, only if the group Participants 11-20 has meet the safety goals. The first dose will be administered via enteral route within 12 hours of life with a target of 6 hours of life. The melatonin will be administered as a single dose for the first 5 participants in allowing the investigators to determine if the dosing frequency has the potential to decrease in the elimination with hypothermia. The next 5 subjects who will receive multiple doses if there are not any safety concerns. Additionally, the participants will have the following test performed: Magnetic Resonance Imaging (MRI), Neurological Outcome Assessment, Pharmacokinetics, and safety monitoring.

Primary Outcome Measure

To identify the maximum tolerated dose of Melatonin [ Time Frame: Changes in Baseline to day 3 ]

Central Contacts

• Alison A McMurray, M.A.M.C.
  3526275016
  [email protected]
• Kristine Boykin, BSN
  3522738706
  [email protected]

Locations (2)

Find similar trials in Gainesville, FL

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