COVID-19 studies are our top priority. For all other trials, there is a 4-week delay in processing a trial submitted/resubmitted to the ANZCTR and additional delays for updates of registered trials. We appreciate your patience.

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
ACTRN12620000026921p
Ethics application status
Submitted, not yet approved
Date submitted
27/11/2019
Date registered
17/01/2020
Date last updated
17/01/2020
Date data sharing statement initially provided
17/01/2020
Type of registration
Prospectively registered

Titles & IDs
Public title
Seeding throUgh FeediNg: nourishing the infant microbiome to support immune health
Scientific title
Seeding throUgh FeediNg: nourishing the infant microbiome to support immune health 'The SUN' randomised controlled trial
Secondary ID [1] 299683 0
None
Universal Trial Number (UTN)
U1111-1244-9285
Trial acronym
SUN Study
Linked study record
ACTRN12618000157279 is the identifier for the feasibility study that preceded this present study and gave guidance on how to conduct this larger RCT.
The study design and prebiotic intervention for the present study have been modeled on findings from the feasibility study, where the prebiotic intervention proved to be an acceptable food to be introduced to infants at around 6 months of age.

Health condition
Health condition(s) or problem(s) studied:
Immune health 315035 0
Gut microbiome 315036 0
Condition category
Condition code
Diet and Nutrition 313365 313365 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is a double-blind, randomised controlled, parallel design that randomises 300 infants, that have not yet started complementary feeding to one of two experimental groups receiving a daily prebiotic food intervention with different levels of resistant starch (RS); intervention (RS2) and a comparator control (RS1) (n=150 per group). The prebiotic intervention will be a freeze-dried kumara powder, where the starch component has been retrograded through cooking and cooling processes to increase the amount of resistant starch.

The allocated prebiotic food intervention is intended to commence as soon as parents /caregivers introduce the first complementary food to their child (i.e. around 6 months of age), according to The New Zealand Ministry of Health and World Health Organisation recommended age for introducing complementary foods, and is to be consumed daily (approx. 5 g kumara powder/day, reconstituted to an age-appropriate consistency with water) for a period of 6 months, until the child is approximately 12-months-of-age. The prebiotic intervention can be eaten alone or mixed into foods and is provided in a form that is safe for infants to consume ad libitum, where the required daily amount will not displace other foods of important nutrient composition in the infant’s diet. Parents/caregivers will be supplied with all the prebiotic intervention food for participation in this research for a total of 6 months.

Adherence to the intervention will be measured using a prospective daily record completed by parents/caregivers and information from a monthly questionnaire on the average amount of the prebiotic intervention food consumed per day in the previous month.
Intervention code [1] 315949 0
Prevention
Comparator / control treatment
One hundred (n=150) children will be randomised into the comparator control (RS1), to be consumed daily for a period of 6 months, until the child is approximately 12-months-of-age. The comparator control is standard freeze-dried kumara powder, as was used in the feasibility study (ACTRN12618000157279). Participants are to consume approx. 5 g kumara powder/day (reconstituted to an age-appropriate consistency with water. for a period of 6 months, until the child is approximately 12-months-of-age. The kumara paste can be eaten alone or mixed into foods. Parents/caregivers will be supplied with all the comparator control prebiotic for participation in this research for a total of 6 months and will be supplied in 3 monthly allocations.

The comparator control prebiotic is provided in a form that is safe for infants to consume ad libitum, where the required daily amount will not displace other foods of important nutrient composition in the infant’s diet.

As for the intervention, adherence to the comparator prebiotic control will be measured using a daily record completed by parents/caregivers prospectively and information from a monthly questionnaire on the average amount of the prebiotic intervention food consumed per day in the previous month.
Control group
Active

Outcomes
Primary outcome [1] 321847 0
Infant stool samples to assess the extent to which the complementary feeding has modulated the infant microbiota. Samples obtained using standard collection methods for safe collection and storage of samples
Timepoint [1] 321847 0
Measured when the infant is 4-6 months of age, 9 months of age, and 12 months of age
Secondary outcome [1] 376459 0
Infant health status using daily records of illness (reporting incidence, severity and duration) and medical records from GP/health practitioners will be obtained for infection-related medical visits, medication use, and hospitalisation events between the ages of 6 and 12 months.
Timepoint [1] 376459 0
Measured when the infant is 4 to 6 months of age, 9 months of age, and 12 months of age
Secondary outcome [2] 376576 0
Height assessed by measuring mat
Timepoint [2] 376576 0
Measured when the infant is 4 to 6 months of age, 9 months of age, and 12 months of age
Secondary outcome [3] 376577 0
Weight assessed by infant scales
Timepoint [3] 376577 0
Measured when the infant is 4 to 6 months of age, 9 months of age, and 12 months of age
Secondary outcome [4] 376578 0
Venepuncture blood sample collected by a trained paediatric phlebotomist to measure protective antibody responses to the oral rota virus
Timepoint [4] 376578 0
Measured with the infant is < 4 months of age, and around 12 months of age
Secondary outcome [5] 376579 0
Breast milk samples from mothers who are breastfeeding during the study (optional). Samples will be used to assess vaccine-specific titre quantification and the role of secretory IgA (sIgA) factors in shaping the gut microbiota. Samples will be collected using standard collection methods for obtaining and safe storage of expressed breast milk samples.
Timepoint [5] 376579 0
Measured with the infant is < 4 months of age, around 9 months of age, and around 12 months of age
Secondary outcome [6] 376580 0
Infant dietary intake using a food frequency questionnaire and 3 day weighed food records
Timepoint [6] 376580 0
Measured with the infant is around 9 months of age, and around 12 months of age
Secondary outcome [7] 376581 0
Maternal dietary intake using a food frequency questionnaire and 24 hour recalls
Timepoint [7] 376581 0
Measured at baseline
Secondary outcome [8] 376582 0
Maternal stool samples to assess the relationship between maternal microbiota and infant microbiota
Timepoint [8] 376582 0
Measured at baseline
Secondary outcome [9] 377892 0
Venepuncture blood sample collected by a trained paediatric phlebotomist to measure protective antibody responses to the intramuscular pneumococcal vaccinations.
Timepoint [9] 377892 0
Measured with the infant is < 4 months of age, and around 12 months of age

Eligibility
Key inclusion criteria
Healthy infants under 4 months of age and their mothers are able to enroll with the expectation that the infants will be introduced to their first complimentary foods before 6 months of age, as per the New Zealand Ministry of Health Food and Nutrition Guidelines.
Minimum age
2 Months
Maximum age
6 Months
Gender
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Infants will be ineligible for enrollment if they:
Were born <32 weeks’ gestation;
Have a developmental disability (i.e.,autism, intellectual disability);
An illness likely to influence their nutritional status (e.g., a chronic illness known to cause malabsorption, digestive or metabolic disorders);
Have health conditions that affect feeding;
Are undergoing treatment with antibiotics;
Are receiving a supplement with a pre and/or probiotic;
Or whose parents written or spoken English comprehension is likely to make participation difficult for them.

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)
The randomisation list will be prepared by a statistician working independently of the study team. The numbers will be supplied to the food manufacturer, where an independent person not involved in the research will place labels on the prebiotic intervention. The researchers will be blinded to this process and the allocation sequence will be concealed throughout the trial.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Approximately 100 infants will be randomised into each of experimental groups (RS2, RS3) and comparator control (RS1) at a 1:1:1 ratio, using computer-generated randomisation sequences.
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
Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Comparisons of differences in the main trial outcomes between the intervention groups and comparator control will be the focus of the statistical analyses. Analysis will be by intention-to-treat (where participants are analysed according to their allocated treatment arm). This will include all participants where a valid outcome is obtained at follow up. Population demographic and baseline characteristics will be summarised according to treatment allocation using descriptive statistics. Categorical variables will be described as frequencies and percentages and continuous variables describes as mean and standard deviation (SD). Both parametric and non-parametric tests will be performed, depending on the distribution of the data.

A secondary analysis of outcomes will be conducted using a per-protocol (PP) population. Inclusion in the PP population and analysis will be based on degree of intervention compliance, define as the total number of days where less than the pre-defined amount of intervention food was consumed per day within the last study month. This information will be determined using a monthly intervention adherence record completed by parents or caregivers. Adherence will be defined as consumption of 1 tsp of the intervention food per day on 80% of the days within the monitored interval.

A random-effects mixed model will be used to account for repeated measured on the same participants and take into account any missing data in maximum likelihood estimates. Adjusted regression analysis will be conducted on all valid data collected at CF3 and CF6, controlling for baseline outcome value.. Model-adjusted treatment effect will be estimated at CF3 and CF6 separately using an interaction term between groups and months. The consistency of the short and long-term effects of the dietary intervention will be assessed using the interaction p-value. All statistical tests will be 2-sided at the 5% significant level. A detailed statistical analysis plan will be written prior to study completion and final analysis. This will include the planned analysis for the primary outcome and all proposed secondary outcomes and subgroup analyses.

We will analyse the full CT data by both classical group comparisons and longitudinally, with every child being analysed individually, before and after the prebiotic complementary feeding. This latter analysis is expected to deliver microbial, immune and health trajectories across the weaning period. Integrated analysis of the multi-omics data from multiple platforms will be performed to visualize and interpret changes according to biological pathways and networks. This will be performed using software tools such as Ingenuity Pathway Analysis (IPA), mixOmics [Le Cao 2009], and metaCyc [Caspi 2014]. In additional to classical case/control analyses (RCT), every infant will not only be sampled but also analysed before and after the “prebiotic” feeding, i.e. being assessed as a case/control pair. [Lillie 2011].

Recruitment
Recruitment status
Not yet 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 outside Australia
Country [1] 21977 0
New Zealand
State/province [1] 21977 0
Auckland

Funding & Sponsors
Funding source category [1] 304160 0
Government body
Name [1] 304160 0
Ministry of Business, Innovation and Employment Science Challenge
Address [1] 304160 0
15 Stout Street, Wellington 6011
PO Box 1473, Wellington 6140
Country [1] 304160 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland, Faculty of Medical and Health Science
Address
85 Park Road
Grafton
Auckland 1023
Country
New Zealand
Secondary sponsor category [1] 304647 0
None
Name [1] 304647 0
Address [1] 304647 0
Country [1] 304647 0

Ethics approval
Ethics application status
Submitted, not yet approved
Ethics committee name [1] 304637 0
Health and Disabilities ethics Committee
Ethics committee address [1] 304637 0
Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington 6145
Ethics committee country [1] 304637 0
New Zealand
Date submitted for ethics approval [1] 304637 0
05/12/2019
Approval date [1] 304637 0
Ethics approval number [1] 304637 0

Summary
Brief summary
The SUN Study is a double-blind, randomised, comparator controlled trial. Three hundred healthy infants < 4-months-of-age will be recruited and randomised into one of two experimental groups or a comparator control. Participants will receive a daily prebiotic food intervention with varying levels of resistant starch, introduced with their first complementary food for 6 months, as part of a whole diet. The aim of the SUN Study is to determine the associations, and possible causality between prebiotic feeding, growth of immune health-beneficial microbes in the infant gut, with reduced number of respiratory infections and improved vaccination responses. This study will be conducted in Auckland, New Zealand.
Trial website
www.nourishtoflourish.auckland.ac.nz
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97674 0
Prof Clare R Wall
Address 97674 0
Academic Director Nutrition and Dietetics
Discipline of Nutrition,
School of Medical Science
Medical School Campus
University of Auckland
Private Bag 92019
Auckland 1142
Country 97674 0
New Zealand
Phone 97674 0
+64 9 923 9875
Fax 97674 0
Email 97674 0
c.wall@auckland.ac.nz
Contact person for public queries
Name 97675 0
Ms Hannah Eriksen
Address 97675 0
Project Manager
Discipline of Nutrition
School of Medical Science
Medical School Campus
University of Auckland
Private Bag 92019
Auckland 1142
Country 97675 0
New Zealand
Phone 97675 0
+64 9 923 9875
Fax 97675 0
Email 97675 0
a.lovell@auckland.ac.nz
Contact person for scientific queries
Name 97676 0
Prof Clare R Wall
Address 97676 0
Academic Director Nutrition and Dietetics
Discipline of Nutrition,
School of Medical Science
Medical School Campus
University of Auckland
Private Bag 92019
Auckland 1142
Country 97676 0
New Zealand
Phone 97676 0
+64 9 923 9875
Fax 97676 0
Email 97676 0
c.wall@auckland.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
No IPD sharing has been approved under the ethics approval for this study.
What supporting documents are/will be available?
No other documents available
Summary results
No Results