MIND - Melatonin Neuroprotection Dosage Study

Melatonin as a Novel Neuroprotectant in Preterm Infants - Dosage Study

Purpose of study and objectives

The overall purpose is to investigate whether melatonin, on achieving adult maternal peak blood levels in preterm infants, will reduce brain injury and white matter disease as defined by specialised magnetic resonance (MR) imaging at term. Before testing this hypothesis in a clinical trial, the dose of melatonin required to achieve the desired concentration in preterm infants needs to be determined. This data will be used in the clinical double blinded randomised trial for which a separate application will be made to the ethics committee.

The principal research objective in this study is to determine the dose required to achieve physiological melatonin blood levels in the preterm infants similar to that of the mother. Secondary objective is to define the pharmacokinetic profile of melatonin in preterm infants.

Study design and methodology

The proposed clinical trial is a single dose, open label, dose escalation pharmacokinetic study in preterm infants less than 31 weeks gestation to achieve adult peak blood concentrations of melatonin (200-250 pmol/L).

The trial will be a multi centre study based in the Neonatal Intensive Care Units of United Kingdom.

Treatment

A single intravenous infusion of melatonin will be given to each infant maximum over 6 hours once in the first 7 days of life. The starting dose is 0.1 microgram/kg/hr which will be increased or decreased incrementally in subsequent groups of infants until the desired melatonin concentration is achieved.

Duration

The duration of treatment will be 6 hours maximum only.

Investigations

Pharmacokinetic assessment will be performed on the blood and urine samples collected at various timepoints appropriate.

Statistical Analysis

Pharmacokinetic assessment will be done using appropriate software.