Melatonin As A Novel Neuroprotectant In Preterm Infants- Dosage Study (MIND)

• ClinicalTrials.gov Identifier: NCT00649961
• Recruitment Status: Completed
• First Posted: April 1, 2008
• Results First Posted: February 28, 2014
• Last Update Posted: August 20, 2019
• Sponsor: Imperial College London
• Collaborator: British Medical Research Council
• Information provided by (Responsible Party): Imperial College London

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Premature Birth; Brain Injury	Drug: Melatonin injection	Phase 2

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.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 18 participants
• Allocation: N/A
• Intervention Model: Single Group Assignment
• Masking: None (Open Label)
• Primary Purpose: Other
• Official Title: Melatonin As A Novel Neuroprotectant In Preterm Infants- Dosage Study
• Study Start Date: May 2010
• Actual Primary Completion Date: February 2011
• Actual Study Completion Date: February 2011

Arms and Interventions

Arm

Intervention/treatment

Experimental: Melatonin Open Label Single Arm; Infants born less than 31 weeks gestation who are less than 7 days old

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.; Other Name: CAS-73314

Outcome Measures

Primary Outcome Measures :

1. 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 ]

Eligibility Criteria

• Ages Eligible for Study: 23 Weeks to 31 Weeks (Child)
• Sexes Eligible for Study: All
• 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

Locations

United Kingdom

Royal Bolton Hospital

Bolton, 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 

Neonatal Research at Imperial College - Website for parents 

UK Medical Research Council- funder for the study 

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.

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 London
• ClinicalTrials.gov Identifier: NCT00649961
• Other Study ID Numbers: CR0970 (MIND); 2007-007156-33 ( EudraCT Number )
• First Posted: April 1, 2008
• Results First Posted: February 28, 2014
• Last Update Posted: August 20, 2019
• Last Verified: August 2019

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Imperial College London:

Premature Birth; Brain injury; Neuroprotection; Melatonin; Pharmacokinetics

Additional relevant MeSH terms:

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