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Trial registered on ANZCTR


Registration number
ACTRN12623000988651
Ethics application status
Approved
Date submitted
17/07/2023
Date registered
11/09/2023
Date last updated
11/09/2023
Date data sharing statement initially provided
11/09/2023
Type of registration
Retrospectively registered

Titles & IDs
Public title
Sheep and Cow Milk Complementary Food Effects on Gut Microbial Diversity - The SMILEY Pilot Study
Scientific title
Sheep and Cow milk Complementary Food Effects on Gut Microbial Diversity in Healthy Infants - SMILEY Pilot Study
Secondary ID [1] 310120 0
None
Universal Trial Number (UTN)
Trial acronym
SMILEY
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Gut microbiota 330689 0
Condition category
Condition code
Diet and Nutrition 327510 327510 0 0
Other diet and nutrition disorders
Oral and Gastrointestinal 327744 327744 0 0
Normal oral and gastrointestinal development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Infants will be randomised 1:1:1 into one of two intervention groups or the control.
Treatment allocation to the two intervention groups will be blinded.

The intervention groups are either an ovine milk oat-based product (OMO) or bovine milk oat-based product (BMO). The intervention products will be packaged in identical sachets and provided as a 4-week supply at the baseline visit.

Dose: Participants will be asked to offer their baby the intervention product daily as per the preparation instructions (12 g powder mixed with 80 mL of cooled boiled water). The product must be prepared fresh each morning, and discard any unused at the end of the day. The intervention product should be stored in the fridge if not consumed in one sitting.

Both intervention products involve the use of accepted ingredients in infant nutrition. They are manufactured in registered facilities and comply with Food Standards Australia and New Zealand guidelines concerning manufacturing standards and compliance with food safety requirements, including allergy management.

The intervention products will be introduced in small amounts with the first signs of interest in food (i.e. around 6 months of age, as per the Dietary Guidelines). The intervention will be provided in a safe form 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. It is a commercially acceptable ingredient in infant food and is feasible for families to store and prepare for the duration of the study.

Parents/caregivers of infants randomised to the OMO or BMO groups will be supplied with all the intervention products for participation in this research (total of 4 weeks). Adherence to the intervention will be measured using a prospective daily record completed by parents/caregivers and information on a fortnightly questionnaire regarding the average amount consumed in the previous fortnight. Adherence will be defined as consumption of the required amount of intervention on 80% of the days within the monitored interval.
Intervention code [1] 326525 0
Prevention
Comparator / control treatment
Participants randomised into the control group will follow general feeding guidelines as per the Healthy Eating Guidelines for New Zealand Babies and Toddlers (0-2 years old) - Ministry of Health, 2021. Participants will receive gift vouchers after completion of the final interview to the value of the intervention products as a token of appreciation for their continued participation.

Participants in the control group do not have to complete an adherence record.
Control group
Active

Outcomes
Primary outcome [1] 335378 0
Exploratory analysis of the difference in change over time of the microbial alpha-diversity and relative abundance of specific microbial species (assessed as a composite primary outcome) at approximately 7 months of age, using shotgun sequencing of metagenetic DNA using Illumina HiSeq platform in conjunction with microbial profiling by pyrotag sequencing of bacteria 16S sRNA gene amplicons. [Follow-up of the infants will be performed at 2 weeks and 4 weeks of the intervention].
Timepoint [1] 335378 0
Baseline (pre-intervention at approximately 6 months of age), 2 weeks and 4 weeks (at approximately 7 months of age) post-commencement of intervention
Primary outcome [2] 335519 0
Exploratory analysis of the difference in change over time of the microbial beta-diversity and relative abundance of specific microbial species (assessed as a composite primary outcome) at approximately 7 months of age, assessed using shotgun sequencing of metagenetic DNA using Illumina HiSeq platform in conjunction with microbial profiling by pyrotag sequencing of bacteria 16S sRNA gene amplicons. [Follow-up of the infants will be performed at 2 weeks and 4 weeks of the intervention].
Timepoint [2] 335519 0
Baseline (pre-intervention at approximately 6 months of age), 2 weeks and 4 weeks (at approximately 7 months of age) post-commencement of intervention
Secondary outcome [1] 424133 0
Difference in change over time of faecal short-chain fatty acids at approximately 7 months of age.
Timepoint [1] 424133 0
Baseline (pre-intervention at approximately 6 months of age), 2 weeks and 4 weeks (at approximately 7 months of age) post-commencement of intervention.
Secondary outcome [2] 424134 0
Length assessed by measuring mat.
Timepoint [2] 424134 0
Baseline (pre-intervention at approximately 6 months of age), 2 weeks and 4 weeks (at approximately 7 months of age) post-commencement of intervention.
Secondary outcome [3] 424135 0
Weight assessed by infant scales.
Timepoint [3] 424135 0
Baseline (pre-intervention at approximately 6 months of age), 2 weeks and 4 weeks (at approximately 7 months of age) post-commencement of intervention.
Secondary outcome [4] 424136 0
The difference in infant sleep as a composite outcome encompassing night-time sleep, day-time sleep and activity, assessed using actigraphy and sleep diaries.
Timepoint [4] 424136 0
Baseline (pre-intervention at approximately 6 months of age), 2 weeks and 4 weeks (at approximately 7 months of age) post-commencement of intervention.
Secondary outcome [5] 424137 0
Differences in feeding tolerance assessed using the validated Infant Gastrointestinal Symptom Questionnaire.

Riley AW, Trabulsi J, Yao M, Bevans KB, DeRusso PA. Validation of a Parent Report Questionnaire: The Infant Gastrointestinal Symptom Questionnaire. Clinical Paediatrics. 2015;54(12):1167-1174.
Timepoint [5] 424137 0
Measured at 6.5 months of age, and 7 months of age.
Secondary outcome [6] 424138 0
Difference in infant dietary intake assessed using 3-day food records.
Timepoint [6] 424138 0
Measured at 6.5 months of age, and 7 months of age.

Eligibility
Key inclusion criteria
Infants will be eligible for participation in the study if they
- Are healthy
- Are between 3-6 months of age
- Were at least 32 weeks gestation at birth
- Are exclusively breastfed
- Will be introduced to their first complimentary foods at around 6 months of age, and not before 4 months of age, as per the New Zealand Ministry of Health Food and Nutrition Guidelines for Infants
- Have parents or legal guardians that can give written informed consent to participate in the study
Minimum age
3 Months
Maximum age
6 Months
Sex
Both males and females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Infants will not be eligible for participation if they:
- Were born <32 weeks gestation
- Were small for gestational age (as they may have special dietary requirements)
- Have a developmental disability (i.e., autism, intellectual disability)
- Have an illness likely to influence their nutritional status (e.g., a chronic illness known to cause malabsorption, any digestive or metabolic disorders)
- Have health conditions that affect feeding
- Are undergoing treatment with antibiotics
- Have had any complementary foods at recruitment
- Are receiving a supplement with a pre-and/or probiotic
- Are on infant formula
- Have parents or legal guardians whose written or spoken English comprehension is likely to make participation difficult.

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)
A statistician working independently of the study team will prepare the randomisation list. An independent person not involved in the research will label the intervention pouches. The researchers will be blinded to this process.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Computer-generated block randomisation with variable block sizes of 3 or 6.
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
Not applicable
Phase
Not Applicable
Type of endpoint/s
Efficacy
Statistical methods / analysis
Participants’ data will be stored in a secure study database (REDCap) and imported to SAS version 9.4 for data analysis at the end of the trial. The final results will be reported in concordance with the CONSORT 2010 statement extension to randomised pilot and feasibility trials (Eldridge SM., et al., 2016) and international good clinical practice (GCP). The trial statistician is Yannan Jiang (YJ).

Demographic and baseline characteristics of all randomised participants will be summarised for each group using descriptive statistics. Categorical variables will be described as frequencies and percentages. Continuous variables will be described as mean and standard deviation (SD) or median and interquartile range (IQR) as appropriate. No formal statistical tests will be conducted to compare the two groups at baseline, as recommended by the CONSORT guidelines.

Recruitment
Recruitment status
Recruiting
Date of first participant enrolment
Anticipated
Actual
23/08/2023
Date of last participant enrolment
Anticipated
31/10/2023
Actual
Date of last data collection
Anticipated
30/11/2023
Actual
Sample size
Target
105
Accrual to date
2
Final
Recruitment outside Australia
Country [1] 25645 0
New Zealand
State/province [1] 25645 0
North Island (excluding Auckland)

Funding & Sponsors
Funding source category [1] 314281 0
Government body
Name [1] 314281 0
Ministry of Business, Innovation and Employment (Science Challenge)
Country [1] 314281 0
New Zealand
Primary sponsor type
University
Name
The University of Auckland, Faculty of Medical and Health Science
Address
85 Park RoadGraftonAuckland 1023
Country
New Zealand
Secondary sponsor category [1] 316223 0
None
Name [1] 316223 0
Address [1] 316223 0
Country [1] 316223 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 313400 0
Northern B Health and Disability Ethics Committee
Ethics committee address [1] 313400 0
Ministry of Health 133 Molesworth Street Wellington 6011
Ethics committee country [1] 313400 0
New Zealand
Date submitted for ethics approval [1] 313400 0
Approval date [1] 313400 0
26/06/2023
Ethics approval number [1] 313400 0
2023 FULL 15547

Summary
Brief summary
The SMILEY RCT is a double-blind, parallel, randomised controlled trial involving 105 infants who have not yet started solids and their parent/caregiver. The food-based intervention (ovine or bovine milk oat-based products) will start around 6 months of age (the recommended age for introducing complementary foods, according to the NZ Ministry of Health and World Health Organisation). The SMILEY study aims to compare the impact of consuming an infant oat-sheep milk product with an infant oat-cow milk product on the infant gut bacteria. We are also interested in exploring how the changes in microbiota may impact digestive comfort and sleep.

Participants will be randomised into one of three groups (35 infants in each group), One group will receive an ovine-milk oat-based product (OMO), and another group will receive a bovine-milk oat-based product (BMO). A third group will be the control group. If randomised into the intervention groups, participants will be asked to gradually introduce the oat-based product until the infant consumes approximately 12 g of powder daily. The intervention product is prepared by mixing 12 g of the powder with cooled boiled water to form an age-and stage-appropriate consistency. Participants will be supplied with all the intervention products required for participation in this study at no cost.. Enough intervention products will be supplied for a fortnight. Gold Field Nutrition, Australia has developed the OMO and BMO intervention products and meets the Food Standards Code- 2.9.2 – Food for Infants. If randomised to the control group, participants will receive a gift voucher to the value of the provided intervention product.

The primary aim of the pilot randomised controlled trial is to determine if there are changes in microbial diversity in faecal samples of infants in response to consuming OMO or BMO in the early stages of weaning. This study will be conducted in Tauranga (Bay of Plenty) New Zealand.
Trial website
https://www.thesmileystudy.auckland.ac.nz/
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 128018 0
Prof Clare Wall
Address 128018 0
Head of DepartmentDepartment of Nutrition and DieteticsSchool of Medical ScienceMedical School CampusUniversity of AucklandPrivate Bag 92019Auckland 1142
Country 128018 0
New Zealand
Phone 128018 0
+64 9 923 9875
Fax 128018 0
Email 128018 0
[email protected]
Contact person for public queries
Name 128019 0
Clare Wall
Address 128019 0
Head of DepartmentDepartment of Nutrition and DieteticsSchool of Medical ScienceMedical School CampusUniversity of AucklandPrivate Bag 92019Auckland 1142
Country 128019 0
New Zealand
Phone 128019 0
+64 9 923 9875
Fax 128019 0
Email 128019 0
[email protected]
Contact person for scientific queries
Name 128020 0
Clare Wall
Address 128020 0
Head of DepartmentDepartment of Nutrition and DieteticsSchool of Medical ScienceMedical School CampusUniversity of AucklandPrivate Bag 92019Auckland 1142
Country 128020 0
New Zealand
Phone 128020 0
+64 9 923 9875
Fax 128020 0
Email 128020 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
No IPD sharing has been approved under the ethics approval for this study.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

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

Documents added automatically
No additional documents have been identified.