Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12618000871246
Ethics application status
Approved
Date submitted
11/05/2018
Date registered
22/05/2018
Date last updated
10/05/2021
Date data sharing statement initially provided
23/08/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Understanding Creatine for Neurological Health in Babies
Scientific title
Circulating and Cerebral Creatine Levels of the Preterm Infant: Implications for Neurological Development.
Secondary ID [1] 294860 0
None
Universal Trial Number (UTN)
Trial acronym
UNICORN Babies
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Preterm Birth 307810 0
Condition category
Condition code
Neurological 306858 306858 0 0
Other neurological disorders
Diet and Nutrition 306859 306859 0 0
Other diet and nutrition disorders
Reproductive Health and Childbirth 306871 306871 0 0
Complications of newborn

Intervention/exposure
Study type
Observational
Patient registry
False
Target follow-up duration
Target follow-up type
Description of intervention(s) / exposure
Observations [1] Measurement of creatine and associated metabolites in plasma, urine and nutrition samples, collected from preterm babies across the duration of their stay within the NICU; [2] MRI/MRS scan at term equivalent age; [3] Developmental follow up assessment at three months term corrected age.
Intervention code [1] 301170 0
Diagnosis / Prognosis
Intervention code [2] 301171 0
Early Detection / Screening
Comparator / control treatment
healthy singleton babies born at term (39-40 weeks gestation)
Control group
Active

Outcomes
Primary outcome [1] 305850 0
Infant creatine levels (composite outcome of plasma, urinary and cerebral measures) at term corrected age. Plasma and urine creatine will be measured using LC-MS, and cerebral creatine measured from an MRI/MRS scan.
Timepoint [1] 305850 0
Term corrected age
Secondary outcome [1] 346773 0
Creatine content of diet (TPN, formula or breastmilk) received by infants during their stay in hospital, measured using LC-MS.
Timepoint [1] 346773 0
term corrected age.
Secondary outcome [2] 346823 0
Neurological outcomes of infants up to 3 month of age. Composite measures of MRI scans, general movements assessment and the DAYC-2 developmental assessment tool.
Timepoint [2] 346823 0
Term corrected age and 3 months of term corrected age.

Eligibility
Key inclusion criteria
1. Singleton babies
2. Provision of Signed and Dated Informed Consent from Parent/Guardian
3. Preterm infants of gestational post maternal age receiving care within the Neonatal Intensive Care Unit at CCDHB, or, healthy term infants at 39-40 weeks gestation from low risk pregnancies delivered at CCDHB.
Minimum age
23 Weeks
Maximum age
40 Weeks
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
1. Babies with major congenital, genetic or chromosomal abnormalities known to affect neurodevelopmental outcomes
2. Hypoxic ischaemic encephalopathy
3. Inborn (proven or suspected) errors of metabolism
4. Fetal growth restriction (birth weight <10th percentile on customised percentiles)

Study design
Purpose
Natural history
Duration
Longitudinal
Selection
Defined population
Timing
Prospective
Statistical methods / analysis

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
28/05/2018
Actual
13/08/2018
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
31/08/2021
Actual
Sample size
Target
100
Accrual to date
82
Final
Recruitment outside Australia
Country [1] 10394 0
New Zealand
State/province [1] 10394 0
Wellington

Funding & Sponsors
Funding source category [1] 299449 0
Charities/Societies/Foundations
Name [1] 299449 0
Cerebral Palsy Alliance
Country [1] 299449 0
Australia
Primary sponsor type
University
Name
Hudson Institute of Medical Research/Monash University
Address
27-31 Wright Street, Clayton, Victoria 3168
Country
Australia
Secondary sponsor category [1] 298745 0
None
Name [1] 298745 0
Address [1] 298745 0
Country [1] 298745 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 300355 0
Central Health and Disability Ethics Committee
Ethics committee address [1] 300355 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 300355 0
New Zealand
Date submitted for ethics approval [1] 300355 0
11/01/2018
Approval date [1] 300355 0
26/04/2018
Ethics approval number [1] 300355 0
18/CEN/17

Summary
Brief summary
Each year around 10% of all babies born in Australia and New Zealand are preterm. Over half of these babies will have acquired brain injury, increasing their risks of developing life-long conditions, such as cerebral palsy. Creatine and its phosphorylated derivative phosphocreatine (PCr) have long been established as having a critical role in neural development and brain metabolism, with creatine deficiency syndromes leading to significant neurological impairments, including mental retardation, expressive speech and language delay, autistic like behaviour and epilepsy. We have evidence from preclinical animal studies to suggest that preterm babies will be creatine deficient due to an immature renal-hepatic axis and inability to make creatine. Our preliminary data from a 26-week preterm infant shows a dramatic fall in plasma creatine concentration over the first week of life, suggesting this baby was unable to maintain creatine homeostasis. These observations taken together raise questions about whether creatine insufficiency predisposes or compounds neurological deficits in preterm infants?

We will utilise non-invasive imaging techniques to measure cerebral creatine levels in preterm infants, to determine any creatine deficiencies in this population. The innovation of this work is that early detection of cerebral creatine deficiency in preterm infants will provide the basis of early intervention with creatine supplementation to avoid cerebral energy deficiency and the ensuing development of poor neurological sequela associated with these deficiencies. If our hypothesis is proven, we stand to revolutinise the nutritional care of preterm infants, directly influence brain function and improve the short and long-term neurological outcomes for these babies.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 83378 0
Dr Max Berry
Address 83378 0
Department of Paediatrics and Child Health, University of Otago Wellington
23A Mein Street
Wellington, New Zealand 6242
Country 83378 0
New Zealand
Phone 83378 0
+64 212449929
Fax 83378 0
Email 83378 0
[email protected]
Contact person for public queries
Name 83379 0
Dr Max Berry
Address 83379 0
Department of Paediatrics and Child Health, University of Otago Wellington
23A Mein Street
Wellington, New Zealand 6242
Country 83379 0
New Zealand
Phone 83379 0
+64 212449929
Fax 83379 0
Email 83379 0
[email protected]
Contact person for scientific queries
Name 83380 0
Dr Stacey Ellery
Address 83380 0
Hudson Institute of Medical Research
27-31 Wright Street, Clayton, Victoria 3168
Country 83380 0
Australia
Phone 83380 0
+61 385722870
Fax 83380 0
Email 83380 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
4200Study protocolBerry, Mary J., et al. "UNICORN Babies: Understanding Circulating and Cerebral Creatine Levels of the Preterm Infant. An Observational Study Protocol." Frontiers in physiology 10 (2019).https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6417365/  375080-(Uploaded-20-08-2019-16-25-20)-Study-related document.pdf



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseUnicorn babies: Understanding circulating and cerebral creatine levels of the preterm infant. An observational study protocol.2019https://dx.doi.org/10.3389/fphys.2019.00142
N.B. These documents automatically identified may not have been verified by the study sponsor.