Melatonin As A Novel Neuroprotectant In Preterm Infants- Dosage Study
Condition: Premature Birth; Brain Injury
MeSH terms: Brain Injuries; Premature Birth
Study type: Interventional
Phase: Phase 2

Summary: 
      Preterm babies are at risk of brain injury. Melatonin, a naturally occurring hormone, may
      reduce this risk. The unborn baby receives melatonin from the mother but following premature
      delivery there maybe a period of prolonged melatonin deficiency. This deficiency may be
      harmful because studies suggest that melatonin is important in protecting the brain and
      reducing the risk of brain injury after preterm birth. The purpose of this study is to find
      the ideal dose of melatonin to give to preterm babies. We intend to study a total of 24
      babies less than 31 weeks gestation and who are less than 7 days old.
    

Detailed description: 
      PURPOSE OF THE 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 imaging (MRI) 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 31weeks 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 in UK.

      TREATMENT A single intravenous infusion of melatonin will be given to each infant 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 only.

      INVESTIGATIONS Pharmacokinetic assessment will be performed on the blood and urine samples
      will be collected 2 hourly at various timepoints.

      STATISTICAL ANALYSIS Pharmacokinetic assessment will be done using appropriate software.
    

Intervention name(s): Melatonin injection
Intervention type(s): Drug
Intervention description(s): A single intravenous infusion of melatonin will be given to each infant over 6 hours so that successive groups will receive increasing doses until the correct dose for age is found.
Based on the pharmacokinetics and clearance of melatonin in adults an approximate dose has been calculated. The starting dose of melatonin will be 0.1 microgram/kg/hr to be given over 6 hours intravenously. The range of expected dose is 0.1-0.5 microgram/kg/hr.
Other intervention name(s): CAS-73314
Intervention MeSH terms: Melatonin
Intervention model: Single Group Assignment
Masking: None (Open Label)
Primary purpose: Other
Keywords: Premature Birth; Brain injury; Neuroprotection; Melatonin; Pharmacokinetics