Melatonin as a Neuroprotective Therapy in Neonates With HIE Undergoing Hypothermia

NCT ID: NCT02621944

Last Updated: 2025-10-02

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

EARLY_PHASE1

Total Enrollment

70 participants

Study Classification

INTERVENTIONAL

Study Start Date

2016-11-30

Study Completion Date

2026-03-31

Brief Summary

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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

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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

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Hypoxic Ischemic Encephalopathy

Study Design

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Allocation Method

NON_RANDOMIZED

Intervention Model

SINGLE_GROUP

Primary Study Purpose

TREATMENT

Blinding Strategy

NONE

Study Groups

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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.

Group Type EXPERIMENTAL

Melatonin

Intervention Type 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

Intervention Type OTHER

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

Pharmacokinetics

Intervention Type OTHER

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

Neurological Outcome Assessment

Intervention Type BEHAVIORAL

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

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.

Group Type EXPERIMENTAL

Melatonin

Intervention Type 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

Intervention Type OTHER

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

Pharmacokinetics

Intervention Type OTHER

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

Neurological Outcome Assessment

Intervention Type BEHAVIORAL

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

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.

Group Type EXPERIMENTAL

Melatonin

Intervention Type 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

Intervention Type OTHER

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

Pharmacokinetics

Intervention Type OTHER

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

Neurological Outcome Assessment

Intervention Type BEHAVIORAL

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

Interventions

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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.

Intervention Type DRUG

Magnetic Resonance Imaging

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

Intervention Type OTHER

Pharmacokinetics

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

Intervention Type OTHER

Neurological Outcome Assessment

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

Intervention Type BEHAVIORAL

Other Intervention Names

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MRI

Eligibility Criteria

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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.
Maximum Eligible Age

6 Hours

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Thrasher Research Fund

OTHER

Sponsor Role collaborator

University of Florida

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael D Weiss, MD

Role: PRINCIPAL_INVESTIGATOR

University of Florida

Locations

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University of Florida

Gainesville, Florida, United States

Site Status RECRUITING

Florida Hospital for Children

Orlando, Florida, United States

Site Status RECRUITING

Countries

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United States

Central Contacts

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

Role: CONTACT

3526275016

Kristine Boykin, BSN

Role: CONTACT

3522738706

Facility Contacts

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

Role: primary

352-627-5016

Michael Weiss, MD

Role: backup

3522738985

Rajan Wadhawan, M.D.

Role: primary

407-303-2528

Other Identifiers

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IRB201500886

Identifier Type: -

Identifier Source: org_study_id

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