Oral Melatonin as Neuroprotectant in Preterm Infants

Melatonin Clinical Trial

Official title:

Oral Melatonin as Neuroprotectant in Preterm Infants .A Prospective, Double Blind vs Placebo, Parallel Arms Study

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04235673
• Other study ID #: 20180004210 17/01/2018
• Status: Completed
• Phase: N/A
• Start date: May 25, 2020
• Est. completion date: October 11, 2022

Study information

• Verified date: October 2022
• Source: IRCCS Policlinico S. Matteo
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 60
• Est. completion date: October 11, 2022
• Est. primary completion date: October 1, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 25 Weeks to 30 Weeks

Eligibility

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

Related Conditions & MeSH terms

• Malondialdehyde
• Melatonin
• Premature Birth

Intervention

Dietary Supplement:
• melatonin
orally administered drops

Drug:
• placebo
orally administered drops

Locations

Country	Name	City	State
Italy	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

Sponsors (3)

Lead Sponsor	Collaborator
Francesca Garofoli	Azienda Socio Sanitaria Territoriale degli Spedali Civili di Brescia, IRCCS National Neurological Institute "C. Mondino" Foundation

Country where clinical trial is conducted

Italy, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Other	Fagan Test of Infant Intelligence (FTII)	Measure the time ( minutes) to recognize unfamiliar versus familiar human faces to gauge visual-spatial encoding, attention, and working memory in infants.	up to 24 months
Other	Griffiths Mental Developmental Scales'Revised (GMDS-R)	The scales rate infant development across 5 main areas (locomotor, personal and social skills, hearing and language, eye and hand co-ordination, and performance), providing a general developmental quotient (DQ) of infants' abilities and 5 subscale quotients (SQ).	up to 24 months
Other	Child Behavior Checklist (CBCL) scales.	A self-rating scale to evaluate emotional, social, and behavioral problems in infants, according to the parents' evaluation.	up to 24 months
Primary	Malondialdehyde	plasmatic concentration pg/ml	15 days
Primary	Melatonin	plasmatic concentration pg/ml	15 days
Secondary	Cranial ultrasound (cUS) Assessment	to identify and score White Matter injuries	up to 40 weeks
Secondary	Brain Magnetic Resonance Immaging (cMRI) Assessment	Identify and score White Matter injuries	up to 40 weeks
Secondary	Auditory brain stem evoked response (ABR) Assessments	Identify and score auditory diseases	up to 40 weeks