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Trial registered on ANZCTR


Registration number
ACTRN12618000157279
Ethics application status
Approved
Date submitted
5/11/2017
Date registered
1/02/2018
Date last updated
1/02/2018
Type of registration
Prospectively registered

Titles & IDs
Public title
Nourish to Flourish - testing the effect of a complementary food fed to infants on gut bacteria and immune health
Scientific title
Good bacteria for healthy babies - Complementary feeding to nourish the microbiome that supports gut health (Phase 1 Feasibility Study)
Secondary ID [1] 293211 0
None
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Immune Health 305211 0
Gut Microbiome 305212 0
Condition category
Condition code
Diet and Nutrition 304524 304524 0 0
Other diet and nutrition disorders

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
This study is a non-randomised clinical pilot study with an active control involving the recruitment of 40 infants (and their mothers) with an aim to examine the feasibility of conducting a large scale randomised controlled clinical trial developed to support immune protection against infection.

Group 1 (10 babies): You must be willing to give your baby a commercially prepared probiotic control that is known to show immune benefit(s) in young children.

Group 2 (30 babies): You must be willing to gradually introduce your baby to the kumara powder over 3 months until they are consuming 5 g (1 tsp) per day.

Intervention: kumara powder or probiotic control

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

Dose: Parents and guardians will be requested to have their infant consume the supplied kumara powder each day for a total of 6 months (i.e. from when the child turns 6 months old until they turn 1 year of age).

Kumara powder: The kumara powder is prepared by mixing it with hot water to form a paste, and adding it to your baby’s food to be consumed at meal times according to your baby's routine. Begin by mixing 0.25 tsp kumara powder with 0.75 ml water (1:3 ratio) and gradually increase the amount of kumara powder mixed with water by 0.25 tsp every 2 weeks until the required 1 tsp (5g) per day is reached. After 3 months in the study (i.e. when you baby is 7 to 9 months of age, your baby should be consuming 5 g of kumara powder each day.

You will be supplied with all the kumara powder required for your participation in this research for the 6 month duration of the study at no cost to you. The kumara powder or probiotic will be supplied to you every 3 month.

The amount of food given to the infant will not displace other foods of important nutrient composition in the infant’s diet.

The infant will be introduced to the kumara powder or probiotic control with their first complementary foods between the ages of 4 to 6 months and will be consumed daily for the 6-month period of the intervention.

Adherence will be measured using information from a monthly questionnaire with parents or guardians on the average amount of kumara powder consumed per day in the previous month.
Intervention code [1] 299467 0
Treatment: Other
Comparator / control treatment
10 infants will receive a commercially available probiotic control (Bifodobacterium Lactis) known to show relevant immune benefit(s).

These 10 infants will serve as a positive control to ensure that our study design and methods in principle can detect probiotic-related immune benefit.

Dose administered: Bifodobacterium Lactis has shown good safety record for use in healthy children under 2 years of age. A daily dose of 1 x 10^9 CFU will be received

Mode of administration: 6 drops of Bifodobacterium Lactis will be mixed into your baby's food. The dose can be prepared and consumed at any meal time according to your baby's feeding routine

Frequency and duration of administration: infants will be required to consume one dose (6 drops) per day mixed into their food for the 6 month duration of the study

Adherence: measured in the same manner as the kumara powder using information from a monthly questionnaire with parents or guardians on the average amount of probiotic consumed per day in the previous month.
Control group
Active

Outcomes
Primary outcome [1] 303764 0
Adherence to recommended doses of kumara powder or probiotic control assessed by monthly questionnaires capturing the average amount of intervention consumed each day
Timepoint [1] 303764 0
Measured when the infant is 4 to 6 months of age, 9 months of age, and 12 months of age
Primary outcome [2] 304210 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 [2] 304210 0
Measured when the infant is 4 to 6 months of age, 9 months of age, and 12 months of age
Secondary outcome [1] 340108 0
Height assessed by measuring mat
Timepoint [1] 340108 0
Measured when the infant is 2 to 3 months of age, 4 to 6 months of age, 9 months of age, and 12 months of age
Secondary outcome [2] 341262 0
Weight assessed by infant scales
Timepoint [2] 341262 0
Measured when the infant is 2 to 3 months of age, 4 to 6 months of age, 9 months of age, and 12 months of age
Secondary outcome [3] 341263 0
Blood samples to measure protective antibody responses to the oral rota virus and intramuscular pneumococcal vaccinations. Samples will be obtained using finger prick collection methods. This is an exploratory outcome
Timepoint [3] 341263 0
Measured with the infant is 2 to 3 months of age, 4 months of age, and 12 months of age
Secondary outcome [4] 341264 0
Maternal dietary intake using a food frequency questionnaire and 3 day weighed food records
Timepoint [4] 341264 0
Measured with the infant is 2 to 3 months of age, 4 months of age, 9 months of age, and 12 months of age
Secondary outcome [5] 341265 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 [5] 341265 0
Measured with the infant is 2 to 3 months of age, 4 months of age, 9 months of age, and 12 months of age
Secondary outcome [6] 341266 0
Urine samples for global metabolic profiling using standard collection methods. This is an exploratory outcome.
Timepoint [6] 341266 0
Measured with the infant is 2 to 3 months of age, 4 months of age, 9 months of age, and 12 months of age
Secondary outcome [7] 341267 0
Breast milk samples from mothers who are breastfeeding during the study (optional). Samples will be used to assess vaccine-specific titre quantification and collected using standard collection methods for obtaining and safe storage of expressed breast milk samples. This is an exploratory outcome.
Timepoint [7] 341267 0
Measured with the infant is 2 to 3 months of age, 4 months of age, 9 months of age, and 12 months of age
Secondary outcome [8] 341268 0
Infant saliva to quantify vaccine-specific antibody responses. This is an exploratory outcome.
Timepoint [8] 341268 0
Measured with the infant is 2 to 3 months of age, 4 months of age, 9 months of age, and 12 months of age
Secondary outcome [9] 341827 0
Infant dietary intake using a food frequency questionnaire and 3 day weighed food records
Timepoint [9] 341827 0
Measured with the infant is 2 to 3 months of age, 4 months of age, 9 months of age, and 12 months of age
Secondary outcome [10] 342541 0
Blood samples to measure global metabolite profiling of responses to the oral rota virus and intramuscular pneumococcal vaccinations. Samples will be obtained using finger prick collection methods. This is an exploratory outcome
Timepoint [10] 342541 0
Measured with the infant is 2 to 3 months of age, 4 months of age, and 12 months of age

Eligibility
Key inclusion criteria
Eligible study participants for the feasibility study are:
Healthy infants 2 to 3 months of age are able to enroll with the expectation that they will be introduced to their first complimentary foods between 4 to 6 months of age, and not before 4 months of age, as per the 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
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
Change in microbiota over time with feeding of kumara powder or probiotic control and their association with health outcomes.

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] 9314 0
New Zealand
State/province [1] 9314 0
Auckland

Funding & Sponsors
Funding source category [1] 297656 0
Government body
Name [1] 297656 0
Ministry of Business, Innovation and Employment Science Challenge
Address [1] 297656 0
15 Stout Street, Wellington 6011
PO Box 1473, Wellington 6140
Country [1] 297656 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] 296678 0
None
Name [1] 296678 0
Address [1] 296678 0
Country [1] 296678 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298740 0
Health and Disabilities ethics Committee
Ethics committee address [1] 298740 0
Ministry of Health
No 1 The Terrace
PO Box 5013
Wellington 6145
Ethics committee country [1] 298740 0
New Zealand
Date submitted for ethics approval [1] 298740 0
09/11/2017
Approval date [1] 298740 0
04/12/2017
Ethics approval number [1] 298740 0
17/NTA/239

Summary
Brief summary
Nourish to Flourish is a non-randomised clinical pilot study with an active control involving 40 infants (and mothers) which will examine the feasibility of conducting a randomised controlled clinical trial (RCT) to support immune protection against infection. This study will be conducted in Auckland, New Zealand

Study Questions:
a) As solid food comprises a relatively small proportion of energy intake in infants during the first few months of complementary feeding, will young infants eat enough of the target whole food or components to potentially alter the GI microbiome and provide protection against infection?
b) What are feasible measures of protection against infection at this age that parents can comply with?
c) How many children would be required to undertake a fully powered clinical trial in Phase 2?
d) Which outcome variables are both relevant and feasible to demonstrate the chain of effects of whole food or food components on immune health benefits?

The primary objectives of this feasibility study are:
• To determine whether infants will consume the target food(s) in a dose estimated to alter immune function via modification of the microbiome and associated metabolite changes.
• To determine the feasibility of the outcome measurements (immune, microbiome, host/microbe metabolome), assess recruitment potential, and identify high prevalence adverse events.
• To determine the number of infants that would be required for an RCT of a complementary feeding intervention for improved immune protection from infection.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78074 0
A/Prof Clare Wall
Address 78074 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 78074 0
New Zealand
Phone 78074 0
+64 9 923 9875
Fax 78074 0
Email 78074 0
c.wall@auckland.ac.nz
Contact person for public queries
Name 78075 0
Miss Amy Lovell
Address 78075 0
Trial Project Manager
Medical School Campus
University of Auckland
Private Bag 92019
Auckland 1142
Country 78075 0
New Zealand
Phone 78075 0
+64 9 923 9875
Fax 78075 0
Email 78075 0
a.lovell@auckland.ac.nz
Contact person for scientific queries
Name 78076 0
Prof Martin Kussman
Address 78076 0
Systems Biology in Nutrition and Health
The Liggins Institute
Private bag 92019
Auckland 1142
Country 78076 0
New Zealand
Phone 78076 0
+64 9 923 3055
Fax 78076 0
Email 78076 0
m.kussmann@auckland.ac.nz

No data has been provided for results reporting
Summary results
Not applicable