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Trial registered on ANZCTR


Registration number
ACTRN12616001571460
Ethics application status
Approved
Date submitted
2/02/2016
Date registered
14/11/2016
Date last updated
22/11/2017
Type of registration
Retrospectively registered

Titles & IDs
Public title
Effect of cow’s milk infant formula on neurodevelopment and growth in infants
Scientific title
Effect of 12-month supplementation of infant and follow-on formula with complex milk lipids on neurodevelopment and growth in healthy term infants
Secondary ID [1] 288195 0
Nil
Universal Trial Number (UTN)
U1111-1177-9120
Trial acronym
CLING
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Infant nutrition

297504 0
Brain Development in term infants 297505 0
Condition category
Condition code
Neurological 297695 297695 0 0
Studies of the normal brain and nervous system
Diet and Nutrition 297721 297721 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The intervention products are infant formula for 0-6 month-old infants and follow-on formula for 6-12 month-old infants. All products comply with GB standard for nutritional composition. Healthy term infants in group 1 receive a infant formula and follow-on formula enriched in complex milk lipids to match the upper end of breast milk levels.
Composition of the infant formula products for group 1 per 100 mL of reconstituted powder formula (67 kcal/100 mL):
Protein 1.7 g, fat 3.4 g, carbohydrate (lactose) 7.4 g, linoleic acid 400 mg, a-linolenic acid 45 mg, prebiotic, probiotic, vitamins and minerals.
Composition of the follow-on formula products for group 1 per 100 kcal of reconstituted powder formula (68 kcal/100 mL):
Protein 2.2 g, fat 3.2 g, carbohydrate (lactose) 7.8 g, linoleic acid 360 mg, prebiotic, probiotic, vitamins and minerals.
Up to 2 weeks of age, infants will be fed 7-8 times 60 mL of formula by their parent or caregiver at home.
Up to 4 weeks of age, infants will be fed 7-8 times 90 mL of formula by their parent or caregiver at home.
Up to 2 months of age, infants will be fed 6-7 times 120 mL of formula by their parent or caregiver at home.
Up to 4 months of age, infants will be fed 5-6 times 150 mL of formula by their parent or caregiver at home.
Up to 6 months of age, infants will be fed 5-6 times 180 mL of formula by their parent or caregiver at home.
Between 6 and 12 months of age, infants will be fed 3-4 times 210 mL of formula by their parent or caregiver at home.
It is expected that weaning foods will be introduced from 6 months.
All infant feeding will be monitored by every scheduled visit, we also will collect and record number of empty cans of formula milk from each infant’s parent throughout the trial.


Intervention code [1] 293806 0
Treatment: Other
Comparator / control treatment
Healthy term infants in group 2 receive an infant formula and follow-on formula with the same volume, energy level, macronutrients and micronutrients as in group 1 but not enriched in complex milk lipids to match lower end of breast milk levels .This formula is on on par with China formulas currently on the market. Recommended volume consumption of formula in group 2 are identical. Similarly, it is expected that weaning foods will be introduced from 6 months.
Group 1 infants will receive an infant formula and follow-on formula containing rich complex milk lipids. Group 2 infants will receive an infant formula and follow on formula with the same volume, energy levels, macronutrients and micronutrients as in the group 1, but not enriched in complex milk lipids, but the complex milk lipids levels in group 2 infant formula and follow-on formula match the lower level of breast milk, e.g human mature milk 12 months.
Linoleic acid and a-linoleic acid are present in both infant formula and follow-on formula for both intervention and control products. All products meet FSANZ and GB standard requirements for infant and follow-on formula, including fatty acid profile.
All empty formula packaging will be returned to the sites. Feeding questionnaires are filled by parents.

Infants will be allocated to the breast-fed group if their mother is able or willing to breast feed exclusively. If the mother cannot or decide not to breast feed, then the infants will be randomly allocated to one of the 2 formula-fed groups to receive either the intervention formula product or the control formula product. The breast-fed group (breast-feeding exclusively for at least 4-6 months) will act as a reference standard group.
Therefore, there are three groups in total. 2 x control groups (1 breastfed group and 1 control formula group) plus 1 x experimental formula group
Control group
Active

Outcomes
Primary outcome [1] 297232 0
Neurodevelopment
The Bayley Scales of Infant and Toddler Development (Bayley II or III) will be used to test neurodeveloping and cognitive function ability of infants.
Timepoint [1] 297232 0
At 12 months of age
Secondary outcome [1] 320419 0
Neurodevelopment

The Bayley Scales of Infant and Toddler Development (Bayley II or III) will be used to test neurodeveloping and cognitive function ability of infants.
Timepoint [1] 320419 0
At 6 months of age
Secondary outcome [2] 320455 0
Growth assessed by anthropometry measurements
Timepoint [2] 320455 0
At birth, 42 days, 4 months, 6 months, 8 months and 12 months of age
Secondary outcome [3] 320456 0
Gut microbiota, assessed by faecal sample metagenomic sequencing.
Timepoint [3] 320456 0
at 42 days and 4 months of age
Secondary outcome [4] 326269 0
Short term memory (Chinese version)

The Bayley Scales of Infant and Toddler Development (Bayley II or III) will be used to test neurodeveloping and cognitive function ability of infants.
Timepoint [4] 326269 0
6 and 12 months of age
Secondary outcome [5] 328931 0
formula tolerance assessed by feeding survey. This survey was designed for this study.
Timepoint [5] 328931 0
42 days, 4 months, 6 months, 8 months and 12 months of age

Eligibility
Key inclusion criteria
Healthy full term infants, born at gestational age between 35 and 41 weeks and with a birth body weight between 2500 and 4000 g

Minimum age
1 Days
Maximum age
21 Days
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Neonates with Apgar score <7
Neonates with a major birth defect or evidence of genetic disease
Preterm infants (less than 35 weeks)
Term infants born less than 2500 g or more than 4000 g.

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)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation)
Infants exclusively breast-fed for at least 4-6 months will be the reference group. It is expected that weaning foods will be introduced from 6 months in this group.
The 1st group of infants will be allocated to the breast-fed group if their mother is able or willing to breast feed exclusively. If the mother cannot or decide not to breast feed, then the infants will be randomly allocated to one of the 2 formula-fed groups to receive either the intervention formula product or the control formula product.
This is a randomized, controlled, double blind clinical trial stratified for gender, of 2 parallel groups; one formula fed experimental group (n=120) and one formula fed control group (n=120). We do not know which group would be enriched in complex milk lipids until the end of study. Therefore we only know the infants who are breast-fed or formula-fed.

Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
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
Power calculation is included and is based on the design of a similar recent study by Timby et al 2014.. The power calculation assumes an effect-size of 4 points (increase) and a standard deviation of 9 points on the Bayley's III test with a power of 90% and significance of 5%, and a dropout rate of 25%.

Recruitment
Recruitment status
Completed
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 outside Australia
Country [1] 7569 0
China
State/province [1] 7569 0
Fujian Province

Funding & Sponsors
Funding source category [1] 292813 0
University
Name [1] 292813 0
Charles Sturt University
Address [1] 292813 0
Boorooma Street,
North Wagga Wagga
NSW
2650
Country [1] 292813 0
Australia
Funding source category [2] 294926 0
Commercial sector/Industry
Name [2] 294926 0
Fonterra
Address [2] 294926 0
Private Bag 11029, Palmerston North 4442, Dairy Farm Road, Fitzherbert, Palmerston North, New Zealand
Country [2] 294926 0
New Zealand
Primary sponsor type
University
Name
Charles Sturt University
Address
Boorooma Street,
North Wagga Wagga
NSW
2650
Country
Australia
Secondary sponsor category [1] 291554 0
None
Name [1] 291554 0
N/A
Address [1] 291554 0
N/A
Country [1] 291554 0
Other collaborator category [1] 278802 0
University
Name [1] 278802 0
Xiamen University
Address [1] 278802 0
No 422, Siming South Road, Xiamen, Fujian, China. 361005
Country [1] 278802 0
China

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 294316 0
Human Ethic Committee, Xiamen University
Ethics committee address [1] 294316 0
No 422, Siming South Road, Xiamen, Fujian, China. 361005
Ethics committee country [1] 294316 0
China
Date submitted for ethics approval [1] 294316 0
03/08/2015
Approval date [1] 294316 0
25/08/2015
Ethics approval number [1] 294316 0

Summary
Brief summary
Complex milk lipids are present in human breast milk and are thought to play an important role in neonatal development. Infant formula based on vegetable oils has lower complex lipid content than breast milk. The proposed study will test if enrichment of infant formula and follow-on formula using dairy ingredients with enhanced levels of complex milk lipids to match the upper end of breast milk levels will have a positive impact on neonatal growth and development.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 62330 0
Prof Bing Wang
Address 62330 0
Charles Sturt University
Locked Bag 588
Boorooma Street
NSW 2678
Australia
Country 62330 0
Australia
Phone 62330 0
+61 2 69334549
Fax 62330 0
+61 2 69332991
Email 62330 0
biwang@csu.edu.au
Contact person for public queries
Name 62331 0
Prof Bing Wang
Address 62331 0
Charles Sturt University
Locked Bag 588
Boorooma Street
NSW 2678
Australia
Country 62331 0
Australia
Phone 62331 0
+61 2 69334549
Fax 62331 0
Email 62331 0
biwang@csu.edu.au
Contact person for scientific queries
Name 62332 0
Prof Bing Wang
Address 62332 0
Charles Sturt University
Locked Bag 588
Boorooma Street
NSW 2678
Australia
Country 62332 0
Australia
Phone 62332 0
+61 2 69334549
Fax 62332 0
+61 2 69332991
Email 62332 0
biwang@csu.edu.au

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary