Trial Review

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been endorsed by the ANZCTR. Before participating in a study, talk to your health care provider and refer to this information for consumers
Trial registered on ANZCTR


Registration number
ACTRN12606000327583
Ethics application status
Approved
Date submitted
27/03/2003
Date registered
27/03/2003
Date last updated
12/05/2023
Date data sharing statement initially provided
23/11/2022
Date results information initially provided
23/11/2022
Type of registration
Retrospectively registered

Titles & IDs
Public title
The DINO Trial
Scientific title
Docosahexaenoic Acid (DHA) for the Improvement of Neurodevelopmental Outcome in Preterm Infants.
Secondary ID [1] 32 0
Perinatal Trials Registry: PTR424
Universal Trial Number (UTN)
Trial acronym
DINO
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Preterm Infants < or = 32 weeks 33 0
Condition category
Condition code
Reproductive Health and Childbirth 39 39 0 0
Childbirth and postnatal care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1. High - DHA feeding practice: mothers diet supplemented with tuna oil capsules 6x 500mg DHA rich tuna oil capsules per day to increase DHA in breast milk. If formula is required a high DHA commercial preterm formula is used.
The intervention will commence within 5 days of the preterm infant commencing enteral feeds and continue until the expected term date (40 weeks post menstrual age).
Follow up will occur at 4, 12 and 18 months corrected age.
Intervention code [1] 1172 0
Other interventions
Comparator / control treatment
2. Standard infant feeding practice. Mothers take 6x500mg placebo soy oil capsules or standard preterm infant formula.
Control group
Placebo

Outcomes
Primary outcome [1] 68 0
Neurodevelopment assessed with the Bayleys Scales of Infant Development (II).
Timepoint [1] 68 0
At 18 months corrected age
Primary outcome [2] 288530 0
The primary outcome for the follow-up study at seven years' corrected age is general intellectual ability (Full Scale IQ) as estimated with the Wechsler Abbreviated Scale of Intelligence (WASI).
Timepoint [2] 288530 0
Seven years' corrected age
Secondary outcome [1] 123 0
Growth
Timepoint [1] 123 0
Will be measured weekly from enrolment until estimated date of delivery (EDD) and then at 4, 12 and 18 months corrected age.
Secondary outcome [2] 124 0
Safety
Timepoint [2] 124 0
Markers of safety, such as episodes of necrotising enterocolitis and days to reach full enteral feeds will be collected and assessed.
Secondary outcome [3] 300397 0
Secondary outcomes include cognitive function, educational progress, behaviour, quality of life, symptoms of asthma and allergy, anthropometrics and blood pressure.
Timepoint [3] 300397 0
Seven years' corrected age

Eligibility
Key inclusion criteria
1. Infants born < or = 32 weeks gestation 2. Signed written informed consent 3. Family/guardians who speak English
Minimum age
No limit
Maximum age
32 Weeks
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
1. Infants with major congenital or chromosomal abnormalities 2. More than 5 days after commencing enteral feeds 3. Lactating mother with blood clotting disorder where tuna oil is contraindicated or regularly taking anticoagulant therapy 4. Participation in other clinical trials involving fatty acid intervention 5. Geographic location 6. Multiple births where not all live born infants are eligible.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Centralised telephone randomisation service
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer generated randomisation schedule with balanced variable blocks, stratified by study site, gender and birthweight.
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Phase 3
Type of endpoint/s
Efficacy
Statistical methods / analysis

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
23/12/2003
Actual
4/04/2001
Date of last participant enrolment
Anticipated
Actual
28/10/2005
Date of last data collection
Anticipated
Actual
10/07/2013
Sample size
Target
640
Accrual to date
Final
657
Recruitment in Australia
Recruitment state(s)
QLD,SA,WA,VIC

Funding & Sponsors
Funding source category [1] 56 0
Government body
Name [1] 56 0
National Health & Medical Research Council
Country [1] 56 0
Australia
Primary sponsor type
Government body
Name
National Health and Medical Research Council
Address
GPO Box 1421 Canberra ACT 2601
Country
Australia
Secondary sponsor category [1] 41 0
None
Name [1] 41 0
Nil
Address [1] 41 0
Country [1] 41 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 361 0
Children Yout and Women's Health Service
Ethics committee address [1] 361 0
72 King William Rd, North Adelaide South Australia 5006
Ethics committee country [1] 361 0
Australia
Date submitted for ethics approval [1] 361 0
Approval date [1] 361 0
09/05/2002
Ethics approval number [1] 361 0
REC973/4/2005
Ethics committee name [2] 362 0
Flinders Medical Centre
Ethics committee address [2] 362 0
Flinders Dr, Bedford Park South Australia 5042
Ethics committee country [2] 362 0
Australia
Date submitted for ethics approval [2] 362 0
Approval date [2] 362 0
09/05/2002
Ethics approval number [2] 362 0
122/023
Ethics committee name [3] 363 0
King Edward Memorial Hospital
Ethics committee address [3] 363 0
374 Bagot Rd, Subiaco Western Australia 6008
Ethics committee country [3] 363 0
Australia
Date submitted for ethics approval [3] 363 0
Approval date [3] 363 0
30/05/2003
Ethics approval number [3] 363 0
EC03-21.4
Ethics committee name [4] 364 0
Royal Women's Hospital
Ethics committee address [4] 364 0
20 Flemington Rd, Parkville Victoria 3052
Ethics committee country [4] 364 0
Australia
Date submitted for ethics approval [4] 364 0
Approval date [4] 364 0
10/06/2003
Ethics approval number [4] 364 0
03/16
Ethics committee name [5] 365 0
Royal Brisbane and Women's Hospita
Ethics committee address [5] 365 0
Butterfield St, Herston Queensland 4029
Ethics committee country [5] 365 0
Australia
Date submitted for ethics approval [5] 365 0
Approval date [5] 365 0
22/09/2003
Ethics approval number [5] 365 0
RWH03/16

Summary
Brief summary
Docosahexaenoic Acid (DHA) is a long chain omega 3 polyunsaturated fatty acid which is important for growth and development. DHA also plays an essential role in the development of the central nervous system and retinal function in infants. Preterm infants are denied the large amount of DHA which is normally delivered via the placenta in the last trimester of pregnancy. The DINO trial is a multi-centre, randomized controlled trial to determine whether increasing the level of DHA in breast milk will improve the developmental outcome of preterm infants who are born less than 32 weeks gestation. Study participants, clinicians and trial personnel will be blinded to treatment allocation.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 35135 0
Prof Maria Makrides
Address 35135 0
Women's and Children's Health Research Institute
72 King William Road
North Adelaide SA 5006
Country 35135 0
Australia
Phone 35135 0
+61 8 8161 6179
Fax 35135 0
+61 8 8239 0267
Email 35135 0
[email protected]
Contact person for public queries
Name 10361 0
Dr Thomas Sullivan
Address 10361 0
South Australian Health & Medical Research Institute,
72 King William St, Adelaide SA 5000
Country 10361 0
Australia
Phone 10361 0
+61 8 8128 4419
Fax 10361 0
Email 10361 0
[email protected]
Contact person for scientific queries
Name 1289 0
Dr Thomas Sullivan
Address 1289 0
South Australian Health & Medical Research Institute,
72 King William St, Adelaide SA 5000
Country 1289 0
Australia
Phone 1289 0
+61 8 8128 4419
Fax 1289 0
Email 1289 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
De-identified, individual participant data (IPD) that underlie the results reported in the primary paper (text, tables, figures and appendices) will be available. Dataset(s) will be limited to those participants and variables that are necessary for completion of the approved research proposal
When will data be available (start and end dates)?
Available after publication with no end date determined
Available to whom?
Data will be available to researchers who provide a methodologically sound research proposal following review and approval by the trial steering committee and completion of a signed data access agreement
Available for what types of analyses?
Data may be shared with researchers who provide a methodologically sound research proposal following review and approval by the trial steering committee and completion of a signed data access agreement
How or where can data be obtained?
All data requests should be made to [email protected]


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
17687Study protocol  [email protected]
17688Statistical analysis plan  [email protected]
17689Other  [email protected] Case report form



Results publications and other study-related documents

Documents added manually
TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
Study results articleYes Makrides M, Gibson RA, McPhee AJ, et al. Neurodeve... [More Details]
Study results articleYes Collins CT, Gibson RA, Anderson PJ, et al. Neurode... [More Details]

Documents added automatically
SourceTitleYear of PublicationDOI
EmbaseSubgroup analyses of a randomized trial of DHA supplementation for infants born preterm with assessments of cognitive development up to 7-years of age: What happens in infants born <29 weeks' gestation?.2023https://dx.doi.org/10.1016/j.plefa.2023.102593
EmbaseConsequences of using chronological age versus corrected age when testing cognitive and motor development in infancy and intelligence quotient at school age for children born preterm.2021https://dx.doi.org/10.1371/journal.pone.0256824
EmbaseDocosahexaenoic acid supplementation of preterm infants and parent-reported symptoms of allergic disease at 7 years corrected age: Follow-up of a randomized controlled trial.2019https://dx.doi.org/10.1093/ajcn/nqz010
EmbaseNeurodevelopmental outcomes at 7 years' corrected age in preterm infants who were fed high-dose docosahexaenoic acid to term equivalent: A follow-up of a randomised controlled trial.2015https://dx.doi.org/10.1136/bmjopen-2014-007314
EmbaseLong-term effect of high-dose supplementation with DHA on visual function at school age in children born at < 33 wk gestational age: Results from a follow-up of a randomized controlled trial.2016https://dx.doi.org/10.3945/ajcn.115.114710
Dimensions AIMaternal supplementation with docosahexaenoic acid during pregnancy does not affect early visual development in the infant: a randomized controlled trial2011https://doi.org/10.3945/ajcn.110.009647
N.B. These documents automatically identified may not have been verified by the study sponsor.