Therapeutic Effects of Maternal Melatonin Administration on Brain Injury and White Matter Disease (PREMELIP)

A

Assistance Publique - Hôpitaux de Paris

Status and phase

Terminated

Phase 3

Phase 2

Conditions

Premature Birth

Treatments

Drug: Melatonin 20 µg

Other: Placebo

Drug: Melatonin 10 µg

Study type

Interventional

Funder types

Other

Identifiers

NCT02395783

P120113

Details and patient eligibility

About

Neurocognitive sequelae observed in preterm represent a major health problem for which there is no preventive treatment approved to date. These effects are the result of a multifactorial brain damage occurring in developing prenatal and perinatal period. Melatonin, the principal hormone secreted by the pineal gland has neuroprotective properties in various experimental animal models of perinatal brain damage level. This hormone readily crosses the placental barrier, its antenatal administration would have a neuroprotective effect in the case of preventive preterm birth before 28 weeks of amenorrhea.

The objective of this study determine the dose of melatonin administered parenterally in prenatal maternal in preterm labor to reduce brain damage in the white matter detected by diffusion tensor imaging (DTI) with statistical spatial analysis (TBSS) to the theoretical term of 40 weeks in children born prematurely.

Full description

Neurocognitive sequelae observed in preterm represent a major health problem for which there is no preventive treatment approved to date. These effects are the result of a multifactorial brain damage occurring in developing prenatal and perinatal period. Melatonin, the principal hormone secreted by the pineal gland has neuroprotective properties in various experimental animal models of perinatal brain damage level. This hormone readily crosses the placental barrier, its antenatal administration would have a neuroprotective effect in the case of preventive preterm birth before 28 weeks of gestation.

The objective of this study determine the dose of melatonin administered parenterally in prenatal maternal in preterm labor to reduce brain damage in the white matter detected by diffusion tensor imaging (DTI) with statistical spatial analysis (TBSS) to the theoretical term of 40 weeks in children born prematurely.

Secondary objectives:

Determine the pharmacokinetics of melatonin administered intravenously in two dosage regimens and after randomization in pregnant women under 28 weeks
Assess the contribution of antenatal injection of melatonin on the incidence of white matter injury detected by conventional brain MRI
Assess the contribution of antenatal injection of melatonin on the rate of neurological sequelae at 2 years corrected age, mortality at 28 days of life and at the end of hospitalization.
Evaluate the adverse effects of melatonin injection
- Selection criteria (inclusion and non-inclusion)

Inclusion criteria:

gestational age between 24 weeks + 0 and 27 weeks + 6 days
Delivery imminent spontaneous defined by cervical dilation greater than or equal to 3 cm and regular contractions, painful (greater than or equal to 2 every 10 minutes) or elective caesarean section.
maternal age ≥18 years at baseline
written consent and
Joining a social security scheme mother and holders of parental authority

Criteria for non-inclusion

Related to the parent criteria:

Delivery Outborn
Magnesium Sulphate injection in mother
Chronic renal and hepatic impairment before pregnancy
Circumstances of maternal or fetal distress requiring emergency cesarean eclampsia, placental abruption, placenta previa bleeding.

Criteria related to the fetus:

diagnosis of antenatal malformation Number of subjects required 60 pregnant women between 24 weeks + 0 and 27 weeks + 6 days
- Search time, duration of participation of each patient Total study duration: 36 months Inclusion period: 12months Duration of participation for a patient 24 months Number of participating centers: 3 Average number of inclusions per month per center: 3
- Methodology Clinical phase Iib, 3-arms, double-blind randomised controlled trial, multicenter
- Exams required specifically for research (blood, biopsy ...)
Treatment: antenatal injection of melatonin ((maximum of 2 doses of 10 mcg or 20 mcg)) against placebo in the delivery room
Reviews:
- Determination of plasma melatonin before, after the injection of melatonin (5 minutes, 1 hour, 3 hours, 4 hours after birth) in the mother
- Determination of plasma melatonin and serotonin in umbilical cord
- Brain MRI with diffusion tensor sequence (spatial analysis statistiqueTBSS) at 40 weeks • Primary endpoint and secondary endpoints

Primary endpoint:

MRI with diffusion tensor sequence (TBSS analysis).

Standard (s) Secondary Outcome (s):

Pharmacokinetics of melatonin in the mother
Determination of plasma melatonin and serotonin in umbilical cord f
Brain lesions by conventional MRI
Neurological Evaluation at the age of 2 years by the revised Brunet-test skimped
Mortality at 28 days of life and at discharge
Tolerance of melatonin in pregnant women

Trial design

Primary purpose

Treatment

Allocation

Randomized

Interventional model

Parallel Assignment

Masking

Double Blind

14 participants in 3 patient groups, including a placebo group

Melatonin dose1

Active Comparator group

Description:

Melatonin 10 µg

Treatment:

Drug: Melatonin 10 µg

Melatonin dose2

Active Comparator group

Description:

Melatonin 20 µg

Treatment:

Drug: Melatonin 20 µg

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Other: Placebo

Trial contacts and locations

1

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