MIND: Melatonin As A Novel Neuroprotectant In Preterm Infants- Dosage Study
Study Details
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 |
|---|---|---|
|
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
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 Names:
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Outcome Measures
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. [6 months]
Eligibility Criteria
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
| Site | City | State | Country | Postal Code | |
|---|---|---|---|---|---|
| 1 | Royal Bolton Hospital | Bolton | United Kingdom | ||
| 2 | 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
Study Documents (Full-Text)
None provided.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.
- CR0970 (MIND)
- 2007-007156-33
Study Results
Participant Flow
| Recruitment Details | We conducted an open label dose ranging study between May 2010 and December 2010 in 3 neonatal intensive care units in the UK. |
|---|---|
| Pre-assignment Detail | Infants born less than 31 weeks gestation and less than 7 days old were eligible for the study, although those with: major congenital malformation; or cystic periventricular leucomalacia or haemorrhagic parenchymal infarcts on cranial enrolment were excluded. |
| Arm/Group Title | Melatonin Open Label Single Arm |
|---|---|
| Arm/Group Description | Open label single arm study, infant born less than 31 weeks gestation and less than 7 days old |
| Period Title: Overall Study | |
| STARTED | 18 |
| COMPLETED | 18 |
| NOT COMPLETED | 0 |
Baseline Characteristics
| Arm/Group Title | Single Arm |
|---|---|
| Arm/Group Description | Open label dose finding study in infants born before 31 weeks gestation and less than 7 days of age |
| Overall Participants | 18 |
| Age, Customized (weeks) [Median (Full Range) ] | |
| Gestation at birth |
26.63
|
| Sex: Female, Male (Count of Participants) | |
| Female |
9
50%
|
| Male |
9
50%
|
| Region of Enrollment (participants) [Number] | |
| United Kingdom |
18
100%
|
Outcome Measures
| Title | To Find the Dose of Melatonin Required to Achieve Physiological Blood Levels in the Preterm Infants Similar to That of the Mother. |
|---|---|
| Description | |
| Time Frame | 6 months |
Outcome Measure Data
| Analysis Population Description |
|---|
| [Not Specified] |
| Arm/Group Title | Single Arm |
|---|---|
| Arm/Group Description | open label dose finding study |
| Measure Participants | 18 |
| Median (Full Range) [pg/ml] |
203.3
|
Adverse Events
| Time Frame | 6 month | |
|---|---|---|
| Adverse Event Reporting Description | ||
| Arm/Group Title | Single Arm | |
| Arm/Group Description | open label dose finding study | |
All Cause Mortality |
||
| Single Arm | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/18 (0%) | |
Serious Adverse Events |
||
| Single Arm | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/18 (0%) | |
Other (Not Including Serious) Adverse Events |
||
| Single Arm | ||
| Affected / at Risk (%) | # Events | |
| Total | 0/18 (0%) | |
Limitations/Caveats
More Information
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
The only disclosure restriction on the PI is that the sponsor can review results communications prior to public release and can embargo communications regarding trial results for a period that is less than or equal to 60 days. The sponsor cannot require changes to the communication and cannot extend the embargo.
Results Point of Contact
| Name/Title | Dr Nazakat Merchant |
|---|---|
| Organization | Imperial College London |
| Phone | 00447825881907 |
| nazakat.merchant@kcl.ac.uk |
- CR0970 (MIND)
- 2007-007156-33