Clinical trial NCT00649961: Melatonin As A Novel Neuroprotectant In Preterm Infants- Dosage Study
Official title: Melatonin As A Novel Neuroprotectant In Preterm Infants- Dosage Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Premature Birth
Brain Injury
Keywords: Premature Birth
Brain injury
Neuroprotection
Melatonin
Pharmacokinetics
Lead sponsor: Imperial College London
Sponsor class: OTHER
Collaborators: name: British Medical Research Council
First posted: 2008-04-01
Enrollment: 18
Sex: ALL
Minimum age (years): 23
Maximum age (years): 31
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: OTHER

Brief 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.

Eligibility criteria: 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.

Primary outcomes:
measure: To Find the Dose of Melatonin Required to Achieve Physiological Blood Levels in the Preterm Infants Similar to That of the Mother.
timeFrame: 6 months
Secondary outcomes:
Other outcomes:
Locations:
city: Bolton
country: United Kingdom
facility: Royal Bolton Hospital
city: London
country: United Kingdom
facility: Imperial College Healthcare NHS Trust
Study officials:
affiliation: Imperial College London
name: David Edwards, FRCPCH
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London
name: Denis Azzopardi, FRCPCH
role: PRINCIPAL_INVESTIGATOR
affiliation: Imperial College London
name: Nazakat Merchant, MRCPCH
role: PRINCIPAL_INVESTIGATOR
References:
citation: Jan JE, Wasdell MB, Freeman RD, Bax M. Evidence supporting the use of melatonin in short gestation infants. J Pineal Res. 2007 Jan;42(1):22-7. doi: 10.1111/j.1600-079X.2006.00398.x.
citation: Volpe JJ. Cerebral white matter injury of the premature infant-more common than you think. Pediatrics. 2003 Jul;112(1 Pt 1):176-80. doi: 10.1542/peds.112.1.176. No abstract available.
citation: Wood NS, Marlow N, Costeloe K, Gibson AT, Wilkinson AR. Neurologic and developmental disability after extremely preterm birth. EPICure Study Group. N Engl J Med. 2000 Aug 10;343(6):378-84. doi: 10.1056/NEJM200008103430601.