Recruiting
Early Phase 1

Melatonin

Sponsor:

University of Florida

Code:

NCT02621944

Conditions

Hypoxic Ischemic Encephalopathy

Eligibility Criteria

Sex: All

Age: 0

Healthy Volunteers: Not accepted

Interventions

Melatonin

Magnetic Resonance Imaging

Pharmacokinetics

Neurological Outcome Assessment

Study Details

Brief 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.

Conditions

Hypoxic Ischemic Encephalopathy

Study ID

NCT02621944

Start date

Nov 9, 2016

Status verified date

Jun, 2026

Completion date

Mar, 2027

Anticipated

Primary completion date

Mar, 2027

Anticipated

Eligibility Criteria

Eligibility Criteria

Sex: All

Age: 0

Healthy Volunteers: Not accepted

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.

Study Design

Enrollment

70 participants

Anticipated

Allocation

Non randomized

Intervention Model

Single group

Primary purpose

Treatment

Interventions and Outcome Measures

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.

Interventions

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.

Magnetic Resonance Imaging

All participants will receive an MRI between 7-12 days of age.

Pharmacokinetics

All participants will receive pharmacokinetics to test the amount of melatonin in the blood.

Neurological Outcome Assessment

All participants will receive the Bayley-III Scores and Subsets for neurological outcome assessments.

Primary outcome measure

  • To identify the maximum tolerated dose of Melatonin [ Time Frame: Changes in Baseline to day 3 ]
  • Bayley-III Index Scores (Cognitive, Language, and Motor) will be used for neurological outcome assessment [ Time Frame: Approximately 18 - 20 Months ]
  • 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) ]
  • 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 ]
  • 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) ]
  • 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) ]

Central Contacts and Locations

Central contacts

Alison A McMurray, M.A.M.C.

3526275016amcmurra@ufl.edu

Kristine Boykin, BSN

3522738706kristineboykin@ufl.edu

Locations

University of Florida

Recruiting

Gainesville, Florida, United States, 32610

Contacts

Alison A McMurray, M.A.M.C.

352-627-5016amcmurra@ufl.edu

Michael Weiss, MD

3522738985weissmd@peds.ufl.edu

Principal Investigator:

Michael D Weiss, MD

Florida Hospital for Children

Recruiting

Orlando, Florida, United States, 32803

Contacts

Rajan Wadhawan, M.D.

407-303-2528Rajan.Wadhawan.MD@flhosp.org

Principal Investigator:

Rajan Wadhawan, MD

More Information

Sponsor

University of Florida

Last update posted

Jun 29, 2026

Last verified

Jun, 2026

Trial information was received from ClinicalTrials.gov and was last updated on 2026-09-10. This information was provided to ClinicalTrials.gov by University of Florida on 2026-06-29.