Melatonin As A Novel Neuroprotectant In Preterm Infants- Dosage Study - Full Text View

Sponsor:	Imperial College London
Collaborator:	British Medical Research Council
Information provided by:	Imperial College London
ClinicalTrials.gov Identifier:	NCT00649961

Purpose

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.

Condition	Intervention	Phase
Premature Birth Brain Injury	Drug: Melatonin injection	Phase I

Study Type:	Interventional
Study Design:	Open Label, Uncontrolled, Single Group Assignment, Pharmacokinetics Study
Official Title:	Melatonin As A Novel Neuroprotectant In Preterm Infants- Dosage Study

Resource links provided by NLM:

MedlinePlus related topics: Traumatic Brain Injury

Drug Information available for: Melatonin

U.S. FDA Resources

Further study details as provided by Imperial College London:

Primary Outcome 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 ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:

To define the pharmacokinetic profile of melatonin in preterm infants. [ Time Frame: 6 months ] [ Designated as safety issue: Yes ]

Estimated Enrollment:	24
Study Start Date:	September 2009
Estimated Study Completion Date:	January 2010
Estimated Primary Completion Date:	January 2010 (Final data collection date for primary outcome measure)

Intervention Details:

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.

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 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.

Eligibility

Ages Eligible for Study:	23 Weeks to 31 Weeks
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

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.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00649961

Contacts

Contact: David Edwards, FRCPCH	02083833326	david.edwards@imperial.ac.uk
Contact: Nazakat M Merchant, MRCPCH	07931231506	nazakat.merchant@imperial.ac.uk

Locations

United Kingdom
Imperial College Healthcare NHS Trust
London, United Kingdom, W12 0HS

Sponsors and Collaborators

Imperial College London

British Medical Research Council

Investigators

Principal Investigator:	David Edwards, FRCPCH	Imperial College London
Principal Investigator:	Denis Azzopardi, FRCPCH	Imperial College London
Principal Investigator:	Nazakat Merchant, MRCPCH	Imperial College London

More Information

Additional Information:

Medicines for Children Regulatory Network- adopted study This link exits the ClinicalTrials.gov site

Neonatal Research at Imperial College - Website for parents This link exits the ClinicalTrials.gov site

UK Medical Research Council- funder for the study This link exits the ClinicalTrials.gov site

Publications:

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. Review.

Volpe JJ. Cerebral white matter injury of the premature infant-more common than you think. Pediatrics. 2003 Jul;112(1 Pt 1):176-80. No abstract available.

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.

Responsible Party:	Imperial College ( Professor David Edwards )
Study ID Numbers:	CR0970 (MIND), EUDRA CT No-2007-007156-33
Study First Received:	March 27, 2008
Last Updated:	March 9, 2009
ClinicalTrials.gov Identifier:	NCT00649961 History of Changes
Health Authority:	United Kingdom: Medicines and Healthcare Products Regulatory Agency; United Kingdom: National Health Service; United Kingdom: Research Ethics Committee

Keywords provided by Imperial College London:

Premature Birth
Brain injury
Neuroprotection
Melatonin
Pharmacokinetics

Additional relevant MeSH terms:

Craniocerebral Trauma
Antioxidants
Pregnancy Complications
Molecular Mechanisms of Pharmacological Action
Obstetric Labor, Premature
Physiological Effects of Drugs
Nervous System Diseases
Obstetric Labor Complications
Wounds and Injuries
Central Nervous System Depressants
Central Nervous System Diseases

Disorders of Environmental Origin
Trauma, Nervous System
Brain Diseases
Protective Agents
Neuroprotective Agents
Pharmacologic Actions
Therapeutic Uses
Melatonin
Brain Injuries
Central Nervous System Agents
Premature Birth

ClinicalTrials.gov processed this record on November 30, 2009