Condition category
Nervous System Diseases
Date applied
29/09/2014
Date assigned
24/10/2014
Last edited
28/10/2014
Prospective/Retrospective
Prospectively registered
Overall trial status
Ongoing
Recruitment status
Recruiting

Plain English Summary

Background and study aims
Therapeutic hypothermia is a medical treatment that lowers a patient’s body temperature in order to help prevent tissue damage due to a lack of oxygen. The reduction in body temperature leads to a slowing of normal metabolic, brain and muscle functions. Slowing down metabolism is known to allow at least partial recovery of body cells. Therapeutic hypothermia has been shown to reduce long-term brain damage (neurological sequelae) in infants who have been asphyxiated as they are being born, but it has to be applied within 6 hours of the baby’s birth to work. Melatonin is a drug most commonly used as a sleeping aid. However, it also has a number of other health benefits, including protecting against brain damage. It is a powerful antioxidant, mopping up free radicals that would otherwise damage body cells and it also reduces inflammation. Here, we want to test if giving asphyxiated newborn babies melatonin and therapeutic hypothermia together will protect the brain more against damage than if using the hypothermia on its own.

Who can participate?
Newborn babies that have had to be resuscitated for longer than 10 minutes and are showing signs of having been asphyxiated.

What does the study involve?
The newborns are randomly allocated into one of two groups. Those in group 1 are given three doses of melatonin within 6 hours of being born over a three-day period. Those in group 2 are given a placebo (dummy) drug. They all undergo therapeutic hypothermia. Blood and urine samples are taken to assess the effects of the asphyxia (measuring inflammatory biochemical markers). The extent of any brain damage is also measured using a number of tests.

What are the possible benefits and risks of participating?
The possible benefits are reduced brain damage and better scores on brain development tests in newborns treated with melatonin. The adverse effects of using melatonin are rare and include headache, irritability, dizziness or drowsiness. No serious adverse events have been described. In children side effects such as nausea, apathy, weight gain, headaches and bedwetting have been described. Treatment with melatonin can be used for long periods of time in children without disturbing development, quality of sleep, sexual development or mental health.

Where is the study run from?
San Cecilio University Hospital, Neonatal Unit (Spain).

When is the study starting and how long is it expected to run for?
November 2014 to November 2017.

Who is funding the study?
Health General Institute: Ministry of Health, Social Services and Equality (Ministerio de Sanidad y consumo) (Spain).

Who is the main contact?
Dr Antonio Jerez Calero

Trial website

Contact information

Type

Scientific

Primary contact

Dr Antonio Jerez Calero

ORCID ID

Contact details

c/Albeniz
11 bis
Cajar
Granada
18199
Spain

Additional identifiers

EudraCT number

2012-000184-24

ClinicalTrials.gov number

Protocol/serial number

2012-000184-24

Study information

Scientific title

Whole body hypothermia + melatonin vs whole body hypothermia + placebo in asphyctic newborns. A multicentric, randomized, controlled and double blind clinical trial

Acronym

WBH+ M or P

Study hypothesis

In asphyctic and cooled newborn we expect that melatonin administration will decrease neurolesive free radicals production and will prevent neurological damage derivated of their anti-inflammatory and oxidative effects.

Ethics approval

Granada Ethics Committee for Biomedical Research, 27/11/2012

Study design

Randomized, controlled, double blind, placebo vs treatment. Multicentric design

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Hospitals

Trial type

Treatment

Patient information sheet

Not available in web format, please use the contact details below to request a patient information sheet

Condition

Nervous System Disease

Intervention

Beginning within first 6 hours of life, newborns under treatment will receive a intravenous perfusion of melatonin. Dosis= 5 mg per Kilogram of weight per day. Duration of the substance treatment= 3 days (equal to hypothermia treatment period) (total doses= 3).

Other newborns will receive placebo. The neonatologist, nursing team or statistics don´t know which treatment have been administered because of a doubled blind design.

Follow up include intensive monitoring at the Neonatal Intensive Care Unit during the critical period of the illness. We´ll take blood and urine samples to determine inflammatory biochemical markers. We will also assess neurological sequelae (standardized tests of psychomotor development, testing, neuroimaging and sensory disturbances and / or refractory seizures)

Intervention type

Drug

Phase

Not Applicable

Drug names

Melatonin

Primary outcome measures

Better scores on neurodevelopment test in cooled newborns treated with melatonin vs placebo at 6 months and 18 months of age

Secondary outcome measures

1. Lower plasmatic concentrations of proinflamatory biomarkers derivated of oxidative stress and neuronal damage
2. Type and of brain damaged areas obtained by Magnetic Resonance Imaging
3. Poor prognosis electroencephalographic patterns at Function Cerebral Monitor
Measured at 3-6 hours, 24 hours, 72 hours and then 7-10 days after birth

Overall trial start date

01/11/2014

Overall trial end date

01/11/2017

Reason abandoned

Eligibility

Participant inclusion criteria

1. Newborns, Gestational age <36 weeks and at least ONE of the following:
1.1. Apgar test poor at 5 minutes from birth
1.2. Need for resuscitation longer than 10 minutes using positive pressure ventilation (bag and mask or endotraqueal tube)
1.3. Ph <7 or BD<16 mmol/L in the worse gasometric result at first 60 minutes from birth (cord, arterial, venous or capillary blood sample)
2. Moderate and severe hypoxic-ischemic encephalopathy:
2.1. Sarnat score >6 points

Participant type

Patient

Age group

Neonate

Gender

Both

Target number of participants

36

Participant exclusion criteria

1. Birth weight <1800 g
2. Gestational age < 36 weeks
3. Newborn older than 6 hours
4. Need for surgery during first 3 days of life
5. Severe congenital malformations
6. Severe multiorganic dysfunction and refractory to treatment

Recruitment start date

01/11/2014

Recruitment end date

01/11/2017

Locations

Countries of recruitment

Spain

Trial participating centre

c/Albeniz, 11 bis
Granada
18199
Spain

Sponsor information

Organisation

San Cecilio University Hospital, Neonatal Unit (Spain)

Sponsor details

Avda. Dr Oloriz
16
Granada
18012
Spain

Sponsor type

Hospital/treatment centre

Website

Funders

Funder type

Government

Funder name

Health General Institute: Ministry of Health, Social Services and Equality (Ministerio de Sanidad y consumo) (Spain)

Alternative name(s)

Funding Body Type

Funding Body Subtype

Location

Results and Publications

Publication and dissemination plan

Not provided at time of registration

Intention to publish date

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes