Oral Melatonin as Neuroprotectant in Preterm Infants

NCT04235673 | Completed DMC

• 1 other identifier: 20180004210 17/01/2018
• Study Type: interventional
• Target: 60
• Locations: 1 country
• Sites: 4

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.

Conditions

Malondialdehyde; Melatonin

Keywords

Preterm neonate; Neuroprotection; Malondialdehyde; Melatonin

Outcome Measures

Primary Outcomes (2)

• Malondialdehyde

  plasmatic concentration pg/ml

  15 days

• Melatonin

  plasmatic concentration pg/ml

  15 days

Secondary Outcomes (3)

• Cranial ultrasound (cUS) Assessment

  up to 40 weeks

• Brain Magnetic Resonance Immaging (cMRI) Assessment

  up to 40 weeks

• Auditory brain stem evoked response (ABR) Assessments

  up to 40 weeks

Other Outcomes (3)

• Fagan Test of Infant Intelligence (FTII)

  up to 24 months

• Griffiths Mental Developmental Scales'Revised (GMDS-R)

  up to 24 months

• Child Behavior Checklist (CBCL) scales.

  up to 24 months

Study Arms (2)

melatonin

EXPERIMENTAL

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

Dietary Supplement: melatonin

placebo

PLACEBO COMPARATOR

oral drops manufactured to mimic melatonin

Drug: placebo

Interventions

melatonin DIETARY_SUPPLEMENT

orally administered drops

Also known as: not reported

melatonin

placebo DRUG

orally administered drops

Also known as: not reported

placebo

Eligibility Criteria

• Age: 25 Weeks - 30 Weeks
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Francesca Garofoli: lead
• IRCCS National Neurological Institute "C. Mondino" Foundation: collaborator
• Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia: collaborator

Study Sites (4)

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

Brescia, BS, 25123, Italy

Location

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

Brescia, BS, 25123, Italy

Location

Fondazione IRCCS Mondino

Pavia, PV, 27100, Italy

Location

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

Pavia, PV, 27100, Italy

Location

Related Publications (1)

• 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.

  PMID: 33482894 DERIVED

MeSH Terms

Interventions

Melatonin

Intervention Hierarchy (Ancestors)

Tryptamines; Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists

Study Officials

• Chryssoula Tzialla, MD

  Fondazione IRCCS Policlinico San Matteo di Pavia

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: SUPPORTIVE CARE
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: PhD, Researcher, Co-PI,

Study Record Dates

• First Submitted: May 23, 2019
• First Posted: January 22, 2020
• Study Start: May 25, 2020
• Primary Completion: October 1, 2022
• Study Completion: October 11, 2022
• Last Updated: July 25, 2024

Record last verified: 2022-10

Data Sharing

• IPD Sharing: Will not share

Locations

IT (4)