Melatonin Levels in Preterm and Term Newborn Infants (MELIP)

This study has been completed.
Sponsor:
Information provided by (Responsible Party):
Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier:
NCT01340417
First received: March 30, 2011
Last updated: September 17, 2013
Last verified: September 2013
  Purpose

The general goal of the present study is to examine the developmental changes caused by melatonin in preterm and term newborns.

The major brain lesions associated with cerebral palsy and cognitive impairment in preterm infants are periventricular white matter damage (WMD). At the present time, despite major improvements in neonatal care, there are no established therapeutic regimens for the treatment of brain lesions in preterms. Melatonin is secreted by the pineal gland; melatonin's neuroprotective action has been well documented in animal experimental models. Neuroprotection is believed to stem from its direct free radical scavenging, indirect antioxidant activities.

Originality Several reports have described melatonin secretion in older children, but only a few have observed melatonin concentrations during the first year of life. Very little is known about the fetal pineal melatonin synthesis and nothing at what prenatal age melatonin synthesis starts. Premature infants have a 3 months delay in the development of melatonin rhythmicity compared to full-term infants. One study found discordant data with decreasing melatonin value around term. The absence of longitudinal study and the low number of children included make the interpretation difficult of the secretion of melatonin at the newborn.

Hypothesis: Infants born before 28 weeks gestation have melatonin deficiency (50pg/ml), compared to newborns at term (100pg/ml).

Study design: prospective, longitudinal, multicenter trial in 3 Neonatal Intensive Care Units in Ile de France. Specific aim is to compare the developmental changes of melatonin in preterm and term newborns (200 infants and their mothers: 4 groups of 50 infants: 24-27GA +6d ; 28-32 GA +6d ; 33-36 GA +6d ; 37-41 GA +6d). Secondary aims are the following:

  • determine Melatonin creatinin excretion in preterm infants
  • correlate between serum melatonin secretion and urinary melatonin and 6-sulfatoxymelatonin excretion
  • determine endogenous melatonin production in the human pineal
  • correlate genetic variations between different levels of melatonin in premature infants
  • assess clinical and neurological outcomes at term Clinical impact The present clinical project is part of a translational approach, expected data for infants born before 28 weeks gestation is melatonin deficiency which should participate in determining the potential use of melatonin as a neuroprotectant in human preterm neonates.

Condition Intervention
Pregnancy Preterm
Other: Measurements of melatonin levels in urine, blood, milk.

Study Type: Interventional
Study Design: Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Screening
Official Title: Melatonin Levels in Preterm and Term Newborn Infants

Resource links provided by NLM:


Further study details as provided by Assistance Publique - Hôpitaux de Paris:

Primary Outcome Measures:
  • Measurements of melatonin levels by radioimmunology [ Time Frame: 3 days if delivery between 34 and 41+6d weeks of gestation ] [ Designated as safety issue: Yes ]
    Primary outcomes are measurements of melatonin levels in urine, blood, milk. These procedures will be made by radioimmunology, to limit data variability. The reasoning will be made in coefficient of variation intra-test for a patient.

  • Measurements of melatonin levels by radioimmunology [ Time Frame: 15 days to 3 months if delivery between 24 and 33+6d weeks of gestation ] [ Designated as safety issue: Yes ]
    Primary outcomes are measurements of melatonin levels in urine, blood, milk. These procedures will be made by radioimmunology, to limit data variability. The reasoning will be made in coefficient of variation intra-test for a patient.


Secondary Outcome Measures:
  • Serum Cortisol concentrations and urinary excretion [ Time Frame: 3 days if delivery between 34 and 41+6d weeks of gestation ] [ Designated as safety issue: Yes ]

    Serum Cortisol concentrations and urinary excretion

    • Assay will use a volume of 20µl
    • Sensitivity is of 15nmol/l

  • Serum Cortisol concentrations and urinary excretion [ Time Frame: 15 days to 3 months if delivery between 24 and 33+6d weeks of gestation ] [ Designated as safety issue: Yes ]

    Serum Cortisol concentrations and urinary excretion

    • Assay will use a volume of 20µl
    • Sensitivity is of 15nmol/l

  • Serum Serotonin level [ Time Frame: 3 days if delivery between 34 and 41+6d weeks of gestation ] [ Designated as safety issue: Yes ]

    Serum Serotonin level:

    Liquid chromatography methods will be used to measure the serotonin rates (5-hydroxytryptamine, 5 HT) blood. The radioenzymatic techniques of reference will be implemented for the measurement of the enzymatic activities of the way of the melatonin (N-acetyl transferase [NAT or AANAT, EC. 2.3.1.5] and hydroxyindole O-methyltransferase [HIOMT or ASMT, EC. 2.1.1.4]) to the level of the blood plates.


  • Serum Serotonin level [ Time Frame: 15 days to 3 months if delivery between 24 and 33+6d weeks of gestation ] [ Designated as safety issue: Yes ]

    Serum Serotonin level:

    Liquid chromatography methods will be used to measure the serotonin rates (5-hydroxytryptamine, 5 HT) blood. The radioenzymatic techniques of reference will be implemented for the measurement of the enzymatic activities of the way of the melatonin (N-acetyl transferase [NAT or AANAT, EC. 2.3.1.5] and hydroxyindole O-methyltransferase [HIOMT or ASMT, EC. 2.1.1.4]) to the level of the blood plates.



Enrollment: 380
Study Start Date: April 2011
Study Completion Date: June 2013
Primary Completion Date: January 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: one label
Measurements of melatonin levels in urine, blood, milk.
Other: Measurements of melatonin levels in urine, blood, milk.
Measurements of melatonin levels in urine, blood, milk.
Other Name: Measurements of melatonin levels in urine, blood, milk.

  Show Detailed Description

  Eligibility

Ages Eligible for Study:   24 Weeks to 41 Weeks
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Mother:

    • Consent forms from mother or guardian
    • Age ≥ 18 years
    • Mother Heath insurance
  • Newborn:

    • Infants born between 24+0 et 41+6 weeks of gestation
    • Infants with informed consent from mother or guardian and mother's social insurance

Exclusion Criteria:

  • Mother:

    • Chronic pathology
    • Treatment: Carbamazepine, betablockers, rifampicin, quinolones, cimetidine, 5-Methoxypsoralen or bergapten, 8- methoxypsoralen (or Methoxsalen), CIRCADIN®
  • Newborn :

    • Congenital malformations
    • Dermatosis
    • Treatment: cimetidine
  Contacts and Locations
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Please refer to this study by its ClinicalTrials.gov identifier: NCT01340417

Locations
France
Hôpital Robert DEBRE
Paris, France, 75019
Sponsors and Collaborators
Assistance Publique - Hôpitaux de Paris
Investigators
Principal Investigator: Valérie BIRAN, MD, PhD Assistance Publique - Hôpitaux de Paris
  More Information

No publications provided

Responsible Party: Assistance Publique - Hôpitaux de Paris
ClinicalTrials.gov Identifier: NCT01340417     History of Changes
Other Study ID Numbers: P091108, 2010-A01024-35
Study First Received: March 30, 2011
Last Updated: September 17, 2013
Health Authority: France: Ministry of Health

Keywords provided by Assistance Publique - Hôpitaux de Paris:
melatonin
preterm
deficiency
neuroprotection

Additional relevant MeSH terms:
Melatonin
Antioxidants
Central Nervous System Agents
Central Nervous System Depressants
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Physiological Effects of Drugs
Protective Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on October 22, 2014