Oral Melatonin as Neuroprotectant in Preterm Infants

NCT ID: NCT04235673

Last Updated: 2024-07-25

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 60 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-05-25
• Study Completion Date: 2022-10-11

Brief Summary

Preterm newborns survival rates are improved, but long-term disabilities are still common. Major destructive focal lesions became less common, the most predominant lesion at present is diffuse white matter (WM damage). Melatonin (ME) serves as a neuroprotectant cerebral ischemia through its potent anti-oxidant/-inflammatory effect. Preclinical studies demonstrated that protects the developing brain by preventing abnormal myelination and inflammatory glial reaction. Clinical studies demonstrated ME ability in reducing brain damage after neonatal Hypoxic Ischemic Encephalopathy (HIE) or preventing neonatal impairments due to antenatal/ post-natal injuries: preeclampsia, IntraUterineGrowthRestriction (IUGR), ventilation, Bronchopulmonary Dysplasia (BPD). ME has a good safety profile with no known adverse effects. This study aims to highlight that ME can prevent brain impairment due to premature birth. ME will be administered orally (3 mg/kg/die for 15 days to neonates born before 29+6 week gestation, in a prospective double blind, randomized vs placebo study, 2 parallel arms. ME and malondialdehyde (MDA), a lipid peroxidation product) levels before and at the end of treatment will be measured . Other outcomes: Cerebral ultrasounds (cUS); cerebral magnetic resonance imaging (cMRI), " Fagan test " eye tracking, ophthalmological, auditory, neurological/cognitive child assessments. Monitoring parental distress, which can influence the neurodevelopmental outcome in preterms.

Detailed Description

About 552.000 infants are born in Italy each year, 1% of them with gestational age under 30 weeks. Survival rates are improved, but long-term disabilities are still common. Major destructive focal lesions became less common, the most predominant lesion at present is diffuse white matter (WM damage). The prevention of neurodevelopmental impairment is a major public health challenge and efforts are needed to test neuroprotective strategies. Melatonin (ME) serves as a neuroprotectant cerebral ischemia through its potent anti-oxidant/-inflammatory effect. Preclinical studies demonstrated that protects the developing brain by preventing abnormal myelination and inflammatory glial reaction. Clinical studies demonstrated ME ability in reducing brain damage after neonatal Hypoxic Ischemic Encephalopathy (HIE) or preventing neonatal impairments due to antenatal/ post-natal injuries: preeclampsia, IntraUterineGrowthRestriction (IUGR), ventilation, Bronchopulmonary Dysplasia (BPD). Ongoing studies are testing in premature neonates and pregnant women its neuroprotective properties. ME has a good safety profile with no known adverse effects.

This study aims to highlight that ME can prevent brain impairment due to premature birth. ME will be administered orally (3 mg/kg/die for 15 days within 96 hours from birth) to neonates born before 29+6 week gestation age (GA), in a prospective double blind, randomized vs placebo study, 2 parallel arms (30 preterm infants each). ME and malondialdehyde (MDA, a lipid peroxidation product) levels will be measured before and at the end of treatment. At birth, within 40 weeks of neonatal age, at 4-6 and at 24 months of age the following examinations are performed: Cerebral ultrasounds (cUS); cerebral magnetic resonance imaging (cMRI), during natural sleep (i.e. adopting sleep deprivation and/or feeding protocols); "Fagan test"eye tracking, ophthalmological, auditory brain stem evoked response (ABR), neurological/cognitive child assessments. Monitoring parental distress, which can influence the neurodevelopmental outcome in preterms.

Conditions

Malondialdehyde; Melatonin

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: SUPPORTIVE_CARE
• Blinding Strategy: DOUBLE

Study Groups

melatonin

melatonin oral drops; 3 mg/kg/day for 15 days

Group Type: EXPERIMENTAL

melatonin

Intervention Type: DIETARY_SUPPLEMENT

orally administered drops

placebo

oral drops manufactured to mimic melatonin

Group Type: PLACEBO_COMPARATOR

placebo

Intervention Type: DRUG

orally administered drops

Interventions

melatonin

orally administered drops

Intervention Type: DIETARY_SUPPLEMENT

placebo

orally administered drops

Intervention Type: DRUG

Other Intervention Names

not reported; not reported

Eligibility Criteria

Inclusion Criteria

• preterm newborns gestational age GA < 29+6 weeks + day
• able to receive min 20ml/kg/day enteral nutrition, within 96 hours from birth
• written informed consent by both the parents.

Exclusion Criteria

• preterm newborns GA > 29+6 weeks + days
• not able to receive enteral nutrition (min 20 ml/kg/die) within 96 hours of life
• infants with genetic and/or congenital metabolic or chronic diseases
• intraventricular hemorrhage (IVH) ≥ III,
• parents refusing to sign a written informed consent

• Minimum Eligible Age: 25 Weeks
• Maximum Eligible Age: 30 Weeks
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

IRCCS National Neurological Institute "C. Mondino" Foundation

OTHER

Sponsor Role: collaborator

Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia

OTHER

Sponsor Role: collaborator

Francesca Garofoli

OTHER

Sponsor Role: lead

Responsible Party

Francesca Garofoli

PhD, Researcher, Co-PI,

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Chryssoula Tzialla, MD

Role: PRINCIPAL_INVESTIGATOR

Fondazione IRCCS Policlinico San Matteo di Pavia

Locations

Child and Adolescence Neuropsychiatry Unit, Children's Hospital "Spedali Civili" of Brescia, 25123 Brescia, Italy.

Brescia, BS, Italy

Neonatal Intensive Care Unit, Children's Hospital, University Hospital "Spedali Civili" Brescia, 25123 Brescia, Italy.

Brescia, BS, Italy

Fondazione IRCCS Mondino

Pavia, PV, Italy

Neonatal Unit and NICU, Radiology, Clinical Chemistry Lab., Fondazione IRCCS Policlinico S. Matteo.

Pavia, PV, Italy

Countries

Italy

References

Garofoli F, Longo S, Pisoni C, Accorsi P, Angelini M, Aversa S, Caporali C, Cociglio S, De Silvestri A, Fazzi E, Rizzo V, Tzialla C, Zecca M, Orcesi S. Oral melatonin as a new tool for neuroprotection in preterm newborns: study protocol for a randomized controlled trial. Trials. 2021 Jan 22;22(1):82. doi: 10.1186/s13063-021-05034-w.

Reference Type: DERIVED

PMID: 33482894 (View on PubMed)

Other Identifiers

20180004210 17/01/2018

Identifier Type: -

Identifier Source: org_study_id