Official Title: “Melatonin As A Novel Neuroprotectant In Preterm Infants- Dosage Study”

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.

Study Type: Interventional

Study Design: Other, Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics Study

Study Primary Completion Date: January 2009

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 single centre study based in the Neonatal Intensive Care Unit of Hammersmith Hospital.

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 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 during the 6 hour infusion.

STATISTICAL ANALYSIS Pharmacokinetic assessment will be done using appropriate software.

Intervention(s) in this Clinical Trial

• Drug: Melatonin injection
  • 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.

Primary Measures

• To find the dose of melatonin required to achieve physiological blood levels in the preterm infants similar to that of the mother.
  • Time Frame: 6 months
    Safety Issue?: Yes

Secondary Measures

• To define the pharmacokinetic profile of melatonin in preterm infants.
  • Time Frame: 6 months
    Safety Issue?: Yes

Inclusion Criteria:

• Infants born less than 31 weeks gestation who are less than 7 days old, after parental consent for participation will be included in the study.

Exclusion Criteria:

• Those with major congenital malformation, or cystic periventricular leucomalacia (cPVL) or haemorrhagic parenchymal infarcts (HPI) on cranial ultrasonography prior to enrolment will be excluded from the study.

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: 23 Weeks

Maximum Age for this Clinical Trial: 31 Weeks

Are Healthy Volunteers Accepted for this Clinical Trial?: No

Lead Sponsor: Imperial College London

Overall Clinical Trial Officials and Contacts

David Edwards, FRCPCH Principal Investigator Imperial College London  

Overall Contact: David Edwards, FRCPCH 02083833326 david.edwards@imperial.ac.uk

Information obtained from ClinicalTrials.gov on August 28, 2008

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00649961

Study ID Number: CR0970 (MIND)

ClinicalTrials.gov Identifier: NCT00649961

Health Authority: United Kingdom: Medicines and Healthcare Products Regulatory Agency

Medicines for Children Regulatory Network- adopted study

Neonatal Research at Imperial College - Website for parents

UK Medical Research Council- funder for the study