Optimising nutrition to improve growth and reduce neurodisabilities in neonates at risk of neurological impairment

ISRCTN	ISRCTN39264076
DOI	https://doi.org/10.1186/ISRCTN39264076
Secondary identifying numbers	9348

Submission date: 08/10/2012
Registration date: 09/11/2012
Last edited: 04/01/2019

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Nervous System Diseases

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English summary of protocol

Background and study aims
Docosahexaenoic acid (DHA), choline and uridine-5-monophosphate are dietary factors known to support healthy brain growth and development. These 'neurotrophic' factors are passed from a mother to her baby during pregnancy, with the highest levels being passed to the baby in the third trimester of pregnancy. Many people have diets lacking in these factors. In addition, babies born prematurely will not receive enough of these factors. Babies at risk of brain impairment may not have enough neurotrophic factors to allow the brain to perform natural repair processes, and to help support healthy brain growth and development. Children with brain impairment can also grow less well than children without brain impairment. The aim of this study is to assess whether or not providing adequate amounts of neurotrophic factors can improve growth and developmental outcome in babies at risk of brain impairment.

Who can participate?
Babies at risk of brain impairment.

What does the study involve?
Newborn babies eligible to join the study will be randomly allocated to receive either an active supplement containing the neurotrophic factors or a placebo (dummy) that does not contain the neurotrophic factors. This supplement will be taken every day for 2 years. Neither the parents nor the research team will know whether the baby is on the active or placebo supplement. All babies in the study will also receive support from the study dietician to make sure that they receive a healthy balanced diet and to provide help and advice with supplement administration. During the 2-year study the growth and developmental progress of each baby will be followed by the research team. Participants will also have a blood test measuring DHA levels at the beginning and end of the study. A magnetic resonance imaging (MRI) and magnetic resonance spectroscopy (MRS) scan assessing brain choline levels will be performed at the beginning of the study and at 3 months of age. A further MRI and MRS scan will also be performed at the end of the study in those children who need a scan for clinical reasons.

What are the possible benefits and risks of participating?
Babies who participate in the study may have improved growth and developmental outcome. The disadvantages of taking part are that the assessments and tests involved will require more time spent in hospital.

Where is the study run from?
Department of Paediatrics, University of Oxford (UK).

When is the study starting and how long is it expected to run for?
The study opened in September 2009 and will recruit participants until December 2012. The study will close in December 2014 when the last children taking part have completed their involvement with the study.

Who is funding the study?
The Castang Foundation (UK).

Who is the main contact?
Bonny Baker

Contact information

Dr Peter Sullivan
Scientific

University of Oxford
Department of Paediatrics
Children's Hospital
John Radcliffe
Headley Way
Oxford
OX3 9DU
United Kingdom

ORCID ID	0000-0002-7085-9879
Email	peter.sullivan@paediatrics.ox.ac.uk

Study information

Study design	Double-blind randomised interventional treatment trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Hospital
Study type	Treatment
Participant information sheet	Not available in web format, please use the contact details to request a patient information sheet
Scientific title	Optimising nutrition to improve growth and reduce neurodisabilities in neonates at risk of neurological impairment: a randomised interventional treatment trial
Study objectives	Dietetic and nutritional intervention that optimises macro and micro-nutrient intake will improve growth and neurodevelopmental outcomes in neonates who are at risk of neurological impairment.
Ethics approval(s)	Oxford Research Ethics Committee, 13/08/2008, ref: 08/H0605/70
Health condition(s) or problem(s) studied	Neurodisabilities in neonates
Intervention	The intervention is in the form of a neurotrophic supplement containing docosahexanoic acid (DHA), uridine mono-phosphate (UMP) and choline, along with supportive vitamins and minerals. The control being used is an iso-caloric, iso-nitrogenous placebo substance. The active supplement or control will be taken daily and added to feed or food. This can be taken orally or via a feeding tube and supplementation will continue for the whole 2 years of the study. Follow Up Length: 24 month(s)
Intervention type	Drug
Pharmaceutical study type(s)
Phase	Not Applicable
Drug / device / biological / vaccine name(s)	Docosahexanoic acid (DHA), uridine mono-phosphate (UMP) and choline
Primary outcome measure	1. Neurodevelopmental outcome as assessed by using the Bayley Scale of Infant Development. A clinically significant improvement translates as ~10 points on the Bayley Scale (assuming Standard Deviation (SD) of ~12) 2. Growth measure as assessed using anthropometry (weight, height, skinfold measurements and head circumference)
Secondary outcome measures	1. Electrophysiology: Visual Evoked Potential and behavioural vision testing - tested at baseline, term (if applicable), 6, 12 and 24 months post entry into study 2. Neuroimaging: changes of brain biochemistry and choline uptake as estimated by Magnetic Resonance Spectroscopy (MRS) at baseline and 3 month follow-up
Overall study start date	01/08/2008
Completion date	04/03/2015

Eligibility

Participant type(s)	Patient
Age group	Neonate
Sex	Both
Target number of participants	Planned Sample Size: 60
Key inclusion criteria	Inclusion will depend on the presence of one or more of the following criteria: Birth ≤30+6 weeks gestation: 1. Small for gestational age - weight <9th centile 2. Grade II, III or IV Germinal Matrix Haemorrhage (GMH) - Intra Ventricular Haemorrhage (IVH) Birth 31-40+28 weeks gestation: 1. Grade II, III or IV Germinal Matrix Haemorrhage (GMH) - Intra Ventricular Haemorrhage (IVH) 2. Magnetic resonance imaging (MRI) scan abnormalities in posterior limb of the internal capsule (PLIC), Basal Ganglia or Thalami, White Matter and Cortex Encephalopathy supported by either: 1. Moderately abnormal amplitude-integrated electroencephalography (aEEG) 2. Sarnat Grade II or III
Key exclusion criteria	Exclusion will depend on the presence of one or more of the following criteria: Birth ≤30+6 weeks gestation: 1. Weight >9th centile 2. Grade I Germinal Matrix Haemorrhage (GMH) - Intra Ventricular Haemorrhage (IVH) 3. Profound hearing loss such that Bayley Assessment cannot be completed 4. Progressive neurological degenerative conditions 5. Gastrointestinal disease which significantly impairs absorption 6. Multiple congenital abnormalities or syndromic associations 7. Parents considered by clinicians to be unable to follow the study protocoL Birth 31-40+28 weeks gestation: 1. Grade I Germinal Matrix Haemorrhage (GMH) - Intra Ventricular Haemorrhage (IVH) 2. Profound hearing loss such that Bayley Assessment cannot be completed 3. Progressive neurological degenerative conditions 4. Gastrointestinal disease which significantly impairs absorption 5. Multiple congenital abnormalities or syndromic associations 6. Parents considered by clinicians to be unable to follow the study protocol
Date of first enrolment	27/10/2010
Date of final enrolment	01/09/2013

Locations

Countries of recruitment

England
United Kingdom

Study participating centres

Oxford University Hospitals NHS Foundation Trust

OX3 9DU
United Kingdom

Royal Berkshire NHS Foundation Trust

RG1 5AN
United Kingdom

Wexham Park (now Frimley Health NHS Foundation Trust)

GU16 7UJ
United Kingdom

Sponsor information

Oxford University Hospital Trust (UK)
Hospital/treatment centre

c/o Heather House
Research and Development Lead
Research and Development Department
Joint Research Office
Block 60
Churchill Hospital
Headington
Oxford
OX3 7LE
England
United Kingdom

Phone	+44 (0)1865 572245
Email	heather.house@ouh.nhs.uk
Website	http://www.ox.ac.uk/
"ROR"	https://ror.org/052gg0110

Funders

Funder type

Charity

Castang Foundation (UK)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	Yes
IPD sharing plan summary	Other
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	The datasets generated and/or analysed during this study will be included in the subsequent results publication

Study outputs

Output type	Details	Date created	Date added	Peer reviewed?	Patient-facing?
Protocol article	protocol	17/03/2015		Yes	No
Results article	results	01/09/2018		Yes	No

Editorial Notes

04/01/2019: The following changes were made to the trial record:
1. Publication reference added.
2. Trial participating centres added.
3. IPD sharing statement added.
4. Recruitment dates added.
5. Overall trial end date changed from 31/12/2014 to 04/03/2015.