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Trial registered on ANZCTR


Registration number
ACTRN12616000053426
Ethics application status
Approved
Date submitted
15/01/2016
Date registered
20/01/2016
Date last updated
6/06/2019
Date data sharing statement initially provided
6/06/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Can omega-3 fatty acids reduce cardiovascular risk in children born with poor fetal growth: the Small baby Omega-3 (SO3) trial
Scientific title
Effects of omega-3 fatty acid supplementation to improve cardiovascular risk markers in children born small-for-gestational-age.
Secondary ID [1] 288328 0
None
Universal Trial Number (UTN)
U1111-1178-5213
Trial acronym
SO3 trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Small-for-gestational-age 297297 0
Increased aortic intima-media thickness 297300 0
Hypertension 297301 0
Condition category
Condition code
Cardiovascular 297494 297494 0 0
Hypertension
Reproductive Health and Childbirth 297495 297495 0 0
Childbirth and postnatal care
Cardiovascular 297518 297518 0 0
Other cardiovascular diseases

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomized into groups to either the fish oil supplement (intervention) or no supplement (control) group from 6 months to 18 months of age.
The fish oil supplement will be provided to participants when infants are 6 months old in an encapsulated form containing 300 mg of omega-3 marine triglycerides (EPA 45mg, DHA 150mg), at a dose designed to achieve an omega-3 index of 8%, the optimum level for cardiovascular health. Parents/guardians will cleave the tail end of the capsule to dispense the liquid content into the infant's food or beverage.
Compliance will be measured by assessing blood fatty acid status and empty supplement bottle return.
Intervention code [1] 293625 0
Prevention
Comparator / control treatment
The control group will not receive a supplement.
Control group
Uncontrolled

Outcomes
Primary outcome [1] 297057 0
Aortic intima-media thickness using an ultrasound machine
Timepoint [1] 297057 0
Aortic intima-media thickness will be measured at birth (enrolment), 6, 12, 18 months of age. The primary timepoint will be at 18 months of age.
Secondary outcome [1] 319928 0
Systolic blood pressure using an automated device (CARESCAPE v100)
Timepoint [1] 319928 0
Systolic blood pressure will be measured at birth (enrolment), 6, 12 and 18 months of age. The primary timepoint will be at 18 months of age.
Secondary outcome [2] 319929 0
Infant weight will be measured as an exploratory outcome. Birth weight will be recorded from the patient medical records. Infant weight at 6, 12 and 18 months will be measured using digital scales (Seca 385 Infant Scales, Hamburg, Germany) from children wearing light clothes, no nappies and no shoes.
Timepoint [2] 319929 0
Weight will be measured at birth (enrolment), 6, 12 and months of age as an exploratory outcome.
Secondary outcome [3] 324009 0
Infant height will be measured as an exploratory outcome
Timepoint [3] 324009 0
Infant's height will be measured at enrolment, 6, 12 and 18 months of age. Two length measurements will be taken supine (Seca 217 Infant Measuring Board, Hamburg, Germany) on a level floor and recorded to the nearest 0.1 cm.
Secondary outcome [4] 330699 0
Autonomic control (heart rate variability) will be measured as an exploratory outcome where heart rate will be recorded using a 3-lead ECG over a total of 15 minutes. Heart rate variability will be determined using the Lab Chart software (version 8, AD Instruments, Australia).
Timepoint [4] 330699 0
Autonomic control will be measured at enrolment, 6, 12 and 18 months of age.
Secondary outcome [5] 330700 0
Cardiac structure and function will be measured as an exploratory outcome using an ultra sound machine
Timepoint [5] 330700 0
Cardiac structure and function will be assessed at enrolment, 6 and 18 months of age

Eligibility
Key inclusion criteria
Infants born at term (>37 weeks gestation) that are small-for-gestational-age (birth weight<10th percentile for sex and gestational age).
Minimum age
No limit
Maximum age
2 Weeks
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Multiple births, infants requiring surgery, illness in infant requiring hospitalization for more than 2 weeks, infants with significant neonatal disease, infants with chromosomal abnormalities or congenital malformations, fish oil contraindicated in mother.

Study design
Purpose of the study
Prevention
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Central computerized randomization system
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Intervention assignment will be via a central computerized system using minimization to balance treatment allocation with respect to hospital, newborn gender, ethnicity (Caucasian; non-Caucasian), gestational age (37-39 weeks; <40 weeks), and birth weight percentile (<3rd percentile; 3rd-10th percentile).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?

The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Given a sample size of 252 participants in each randomized group, and type I error probability of 0.05, this study will have: 88% power to detect a clinically relevant relative reduction in aortic IMT of 0.021 mm; 80% power to detect a population relevant 2.5 mm Hg reduction in systolic blood pressure in the omega-3 intervention group; and greater than 95% power to detect a clinically relevant 3.8 mm Hg reduction in systolic blood pressure. Based on our previous experience, we assume a 12.5% loss to follow-up at age 2 years. Thus, we need to randomize 288 participants per group (576 total).

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
NSW
Recruitment hospital [1] 5045 0
Royal Prince Alfred Hospital - Camperdown
Recruitment hospital [2] 5046 0
The Children's Hospital at Westmead - Westmead
Recruitment postcode(s) [1] 12533 0
2006 - The University Of Sydney
Recruitment postcode(s) [2] 12534 0
2145 - Westmead

Funding & Sponsors
Funding source category [1] 292694 0
Government body
Name [1] 292694 0
National Health and Medical Research Council
Address [1] 292694 0
Level 1
16 Marcus Clarke Street
Canberra ACT 2601
Country [1] 292694 0
Australia
Primary sponsor type
University
Name
The University of Sydney
Address
Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders
D17 The Hub, Charles Perkins Centre
The University of Sydney, Camperdown,
NSW, 2006
Country
Australia
Secondary sponsor category [1] 291433 0
Hospital
Name [1] 291433 0
The Children's Hospital at Westmead
Address [1] 291433 0
The Children's Hospital at Westmead
Cnr Hawkesbury Rd and Hainsworth St Westmead,
NSW 2145
Country [1] 291433 0
Australia
Other collaborator category [1] 278777 0
University
Name [1] 278777 0
University of Turku
Address [1] 278777 0
Research Centre of Applied and Preventative Cardiovascular Medicine,
University of Turku
Kiinamyllynkatu 10
20520 Turku
Country [1] 278777 0
Finland

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294167 0
Sydney Lower Health District Ethics Commirttee (Royal Prince Alfred Hospital Zone)
Ethics committee address [1] 294167 0
Research Development Office
Royal Prince Alfred Hospital
Missenden Road
Camperdown NSW 2050
Ethics committee country [1] 294167 0
Australia
Date submitted for ethics approval [1] 294167 0
10/02/2015
Approval date [1] 294167 0
24/09/2015
Ethics approval number [1] 294167 0

Summary
Brief summary
Low birth weight is an important risk factor for adult ischemic heart disease. Those born small-for-gestational-age (<10th percentile for gestational age and gender) are at the highest risk for adult cardiovascular disease. Children and adults born small for gestational age have increased arterial intima-media thickness – a noninvasive marker of subclinical atherosclerosis, the underlying disease process responsible for the majority of cardiovascular events. Birth weight is inversely associated with blood pressure – a major cardiovascular risk factor, in both children and adults.
Published data from populations of children and young adults suggest that omega-3 fatty acid supplementation will have beneficial effects in reducing arterial intima-medial thickness and systolic blood pressure in children who were born small for gestational age. This hypothesis has not been tested in a randomized controlled trial.
This study is designed to test the effectiveness of omega-3 fatty acid supplementation from 6 to 18 months of age in reducing aortic intima-media thickness and systolic blood pressure in children born small-for-gestational-age. The study will be conducted as an open label randomized controlled trial over a 1 year intervention (when the infant is 6-18 months old) where aortic intima media thickness and systolic blood pressure will be measured at recruitment, 6, 12 and 18 months of age.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 41690 0
A/Prof Michael Skilton
Address 41690 0
Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders
D17 The Hub, Charles Perkins Centre
The University of Sydney, Camperdown,
NSW, 2006
Country 41690 0
Australia
Phone 41690 0
+61 2 8627 1916
Fax 41690 0
Email 41690 0
michael.skilton@sydney.edu.au
Contact person for public queries
Name 41691 0
Dr Jovana Mijatovic
Address 41691 0
Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders
D17 The Hub, Charles Perkins Centre
The University of Sydney, Camperdown,
NSW, 2006
Country 41691 0
Australia
Phone 41691 0
+61 286271341
Fax 41691 0
Email 41691 0
jovana.mijatovic@sydney.edu.au
Contact person for scientific queries
Name 41692 0
A/Prof Michael Skilton
Address 41692 0
Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders
D17 The Hub, Charles Perkins Centre
The University of Sydney, Camperdown,
NSW, 2006
Country 41692 0
Australia
Phone 41692 0
+61 2 8627 1916
Fax 41692 0
Email 41692 0
michael.skilton@sydney.edu.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
When the study was initially conceptualised, participants were informed that "only the (listed) researchers....., the research assistants and research midwives working on this study will have access" to participant data.
What supporting documents are/will be available?
No other documents available
Summary results
No Results