Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12616001447448
Ethics application status
Approved
Date submitted
13/10/2016
Date registered
17/10/2016
Date last updated
17/10/2016
Type of registration
Prospectively registered

Titles & IDs
Public title
The TUMMY Trial - The study of omega-3 supplementation in breast-feeding mums on gut health of their baby
Scientific title
The study of omega-3 supplementation in breast-feeding mums on gut health of their baby
Secondary ID [1] 290321 0
Nil known
Universal Trial Number (UTN)
Trial acronym
The TUMMY Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Microbiome health 300585 0
Condition category
Condition code
Oral and Gastrointestinal 300438 300438 0 0
Normal oral and gastrointestinal development and function
Diet and Nutrition 300439 300439 0 0
Other diet and nutrition disorders
Reproductive Health and Childbirth 300458 300458 0 0
Breast feeding

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Intervention capsule (High omega-3 oil blend)
500mg capsule - 75mg of Eicosapentaenoic acid (EPA) and 250mg of docosahexaenoic acid (DHA) in the form of triglyceride
- each participant will be randomly assigned to either the control or intervention group
- participants will be asked to consume 4 oral capsules (500mg per capsule, 2000mg total/day) per day from randomisation to 12 weeks post-partum
Women will be asked to return unused supplements at 12 weeks post-partum when a spot blood sample is taken. The proportion of capsules returned will serve as a measure of adherence. DHA concentration at the end of intervention will be used as an independent biomarker of adherence.
Intervention code [1] 296134 0
Treatment: Other
Comparator / control treatment
Control capsule (vegetable oil blend) with a small amount (0.05% volume) of fish-oil for masking.
500mg capsule - 40% palmitic acid, 40% oleic acids and 20% linoleic acid (obtained from blending canola (rapeseed), sunflower and palm oil)
- each participant will be radomly assigned to either the control or intervention group
- participants will be asked to consume 4 oral capsules (500mg per capsule, 2000mg total/day) per day from randomisation to 12 weeks post-partum
Women will be asked to return unused supplements at 12 weeks post-partum. The proportion of capsules returned will serve as a measure of adherence.
Control group
Placebo

Outcomes
Primary outcome [1] 299876 0
The primary outcome of the study is to determine whether increasing the supply of omega-3 LCPUFA, chiefly as DHA, to breast-fed term infants in the first 12 weeks after birth alters the composition of their gut microbiome, as indicated by an increase in species diversity and numbers of commensal bacteria (a composite outcome) in stool samples collected from the infants.
Timepoint [1] 299876 0
The composition of the microbiome will be assessed at 12 weeks after birth. Stool samples will also be collected within the first 7 days after birth (before the mother starts taking capsules) for the assessment of the microbiome at baseline.
Secondary outcome [1] 328366 0
To determine the effect of increasing the supply of omega-3 LCPUFA, chiefly as DHA, to breast feeding women on the composition of the maternal gut microbiome (species diversity and numbers as a composition outcome) assessed using stool samples.
Timepoint [1] 328366 0
The composition of the maternal microbiome will be assessed at 12 weeks post-partum. Stool samples will also be collected within the first 7 days post-partum (before the mother starts taking capsules) for the assessment of the maternal microbiome at baseline.
Secondary outcome [2] 328375 0
The study will also establish if DHA supplementation in breast feeding women can improve gut maturation/immune profile (a composite outcome as determined by gene expression profile in epithelial cells isolated from stool samples) in the infants during the first 12 weeks after birth.
Timepoint [2] 328375 0
Gut maturation/immune profile will be assessed at 12 weeks after birth. Stool samples will also be collected within the first 7 days after birth (before the mother starts taking capsules) for the assessment of the gut maturation/immune profile (composite outcome) at baseline.
Secondary outcome [3] 328415 0
The effect of increasing the supply of omega-3 LCPUFA, chiefly as DHA, to breast feeding women on the composition of the breast milk microbiome (species diversity and numbers as a composition outcome) assessed in breast milk samples.
Timepoint [3] 328415 0
The composition of the breastmilk microbiome will be at 12 weeks post-partum. Breast milk samples will also be collected within the first 7 days post-partum (before the mother starts taking capsules) for the assessment of the breast milk microbiome at baseline.

Eligibility
Key inclusion criteria
- Singleton pregnancy
- Intending to exclusively breastfeed for at least 12 weeks post-partum
- Willing to take capsules containing fish-oil
- Willing to attend a follow-up appointment at Flinders Medical Centre at 12 weeks post-partum (end of the intervention)
Minimum age
16 Years
Maximum age
No limit
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
- Known major fetal abnormalities
- Infants birth weight less than 2500 grams
- Caesarean section delivery
- Pre-term delivery (less than 37 completed weeks gestation)
- Taking high dose fish-oil supplements (providing equal to or more than 250mg DHA/day)
- Taking fish-oil supplements (providing less than 250mg DHA/day) and not willing to stop
- Bleeding disorder in which fish-oil is contraindicated
- Participation in other RCTs involving omega-3 LCPUFA supplementation during pregnancy

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)
Women will be approached antenatally and provided with a brief outline of the study. Women who indicate an interest will be screened for eligibility by asking them as series of yes/no questions related to the inclusion/exclusion criteria for this study. Interested women who are eligible to participate based on the information provided will be asked to sign a Screening Consent form, providing consent for us to contact them once they have given birth. The women will be provided with a study card that they can hand to either their midwife/nurse or a family member/friend after giving birth. This card will contain the name of the study and contact details of study staff, so that study staff can be informed when she has given birth.

Women who sign the Screening Consent form will be contacted after delivery and their eligibility to participate will be reconfirmed at this time. Eligible women who are still interested in participating will be provided with further details of the study and given the opportunity to discuss the study with family/friends and ask the research staff any questions they may have about the study. The information sheet will describe the purpose of the study, the procedures to be followed, and the risks and benefits of participation. The research staff will conduct the informed consent discussion and will check that information provided is understood and answer any questions about the study. Consent will be voluntary and free from coercion. .

After randomisation to either the control or intervention group (based on the randomisation schedule), the study staff will collect the allocated study product (from the FMC pharmacy), 3 bottles of 126 x 500mg capsules, and provide this to the mother along with detailed instructions on the number of capsules to be taken, and importance of adherence to the study protocol.

Baseline clinical and demographic data including contact details, age, height, weight, highest level of education, alcohol intake, smoking status, antibiotic administration, use of dietary supplements, and dietary intake will be collected by trial research staff in the Case Report Form.

A dried blood spot and dried breast milk spot (for assessment of baseline fatty acid status) will be collected from the women at this time. Women will also be provided with a hygienic collection kit for collection of a stool sample (for analysis of the gastrointestinal microbiome). Additionally they will be provided with a sterile pot and asked to provide ~10-20 mls of breast milk (for analysis of the breast milk microbiome). A soiled infant nappy will be collected to obtain infant stool for microbiome analysis and intestinal epithelial cell isolation (mother will be provided with a zip-lock bag to place the nappy in before collection by study staff).


Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Women will be assigned to study packs labelled with a unique study number assigned through a computer generated randomisation schedule which is prepared by an independent consultant.

Each study pack will contain either treatment or control capsules, pre-packed according to the randomisation schedule. Participants and their family, care providers, outcome assessors and data analysts will be blinded to randomisation group.
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
This will be a pilot study which includes 45 women/infants pairs in each treatment arm (n=90 women with vaginal deliveries). Women will be screened antenatally and following confirmation of vaginal birth will be consented to the study after delivery of their infant. A total of 90 women will be enrolled to allow for a 33% cessation of breastfeeding or other reasons for non-completion of the study per protocol. Due to the limited number of previous studies which have examined the infant microbiome, it is not possible to conduct a meaningful power calculation for this study. However, this study will be one of the largest studies of the infant microbiome which has been conducted to date, and the data we obtain will make it possible to undertake power calculations for future studies in this area.

All analyses will be performed on an intention-to-treat basis. Principal coordinate analysis (PCoA) using the Bray-Curtis similarity measure will be performed to assess divergence in microbiota in the maternal and infant gut and breast milk between groups using data based on operational taxonomic units defined by a 97% sequence similarity threshold. The significance of the distributions of microbiota in treatment and control groups will be assessed by ANalysis Of SIMilarities (ANOSIM) tests. Following PCoA assessments, SIMPER analysis will be used to determine the contribution of specific taxa to the variance observed and identify taxa whose levels diverge between treatment and control groups. The significance of differences in the relative abundance of these taxa will then be assessed by Mann Whitney tests. A p value of <0.05 will be considered as the level of statistical significance in all analyses. All analyses will follow a pre-specified statistical analysis plan.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
1/11/2016
Actual
Date of last participant enrolment
Anticipated
1/11/2017
Actual
Date of last data collection
Anticipated
1/03/2018
Actual
Sample size
Target
90
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment hospital [1] 6826 0
Flinders Medical Centre - Bedford Park
Recruitment postcode(s) [1] 14488 0
5042 - Bedford Park

Funding & Sponsors
Funding source category [1] 294705 0
Commercial sector/Industry
Name [1] 294705 0
BASF
Country [1] 294705 0
Singapore
Primary sponsor type
University
Name
University of Adelaide
Address
North Terrace
Adelaide
South Australia 5005
Country
Australia
Secondary sponsor category [1] 293549 0
None
Name [1] 293549 0
Address [1] 293549 0
Country [1] 293549 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296126 0
Southern Adelaide Clinical Human Research Ethics Committee
Ethics committee address [1] 296126 0
Ward 6C, Room 6A219
Flinders Medical Centre
Flinders Drive, Bedford Park SA 5042
Ethics committee country [1] 296126 0
Australia
Date submitted for ethics approval [1] 296126 0
28/06/2016
Approval date [1] 296126 0
13/09/2016
Ethics approval number [1] 296126 0
301.16

Summary
Brief summary
The gastrointestinal tract is host to a vast number of bacterial species outnumbering the cells of the organism by around 100 fold. The importance of the gut flora (or microbiota) is increasingly being recognised. There is now compelling evidence that the composition of the microbiota in the human gastrointestinal tract (the microbiome) plays an integral role in human health and disease and that altering its composition can have a profound impact on an individual’s metabolic and immune profile.
The first few weeks and months of life are known to be critical for the establishment of the gut microbiome, however there is currently limited knowledge of the factors which regulate this development. The omega-3 LCPUFA, DHA, has been shown to promote the colonisation of the gut by beneficial bacteria, and promote gut development, in adult humans, older infants and in animal studies. While breast milk contains some DHA, the amount it contains is directly related to the amount consumed by the mother, and most breastfeeding women in Australia have a low dietary DHA intakes. Therefore, this study aims to determine whether increasing the amount of DHA in breast milk, by providing DHA supplements to breastfeeding women, will promote the colonisation of the infant gut with beneficial bacterial species over the first 3 months of life. The results have the potential to identify a safe and effective approach for promoting the establishment of the healthiest possible gut microbiome in breast-fed infants, something which is known to have both short- and long-term health benefits.
Trial website
Trial related presentations / publications
Public notes
Attachments [1] 1167 1167 0 0
/AnzctrAttachments/371649-The Tummy Trial Antenatal Screening & Eligibility Checklist .docx (Participant information/consent)
Attachments [2] 1168 1168 0 0
/AnzctrAttachments/371649-The Tummy Trial PICF - UPDATED.doc (Participant information/consent)
Attachments [3] 1169 1169 0 0
/AnzctrAttachments/371649-301.16 General Research Approval Letter.pdf (Ethics approval)

Contacts
Principal investigator
Name 69654 0
A/Prof Beverly Muhlhausler
Address 69654 0
School of Agriculture, Food and Wine
University of Adelaide, Waite Campus
GS 20 Waite Building
Urrbrae SA 5064
Country 69654 0
Australia
Phone 69654 0
+61 (08) 8313 0848
Fax 69654 0
+61 (08) 8313 7135
Email 69654 0
[email protected]
Contact person for public queries
Name 69655 0
Ms Chloe Douglas
Address 69655 0
Child Nutrition Research Centre
Level 4, Flinders Medical Centre
Flinders Drive
Bedford Park SA 5042
Country 69655 0
Australia
Phone 69655 0
+61 404 313 322
Fax 69655 0
Email 69655 0
[email protected]
Contact person for scientific queries
Name 69656 0
Ms Chloe Douglas
Address 69656 0
Child Nutrition Research Centre
Level 4, Flinders Medical Centre
Flinders Drive
Bedford Park SA 5042
Country 69656 0
Australia
Phone 69656 0
+61 404 313 322
Fax 69656 0
Email 69656 0
[email protected]

No information has been provided regarding IPD availability


What supporting documents are/will be available?

Current supporting documents:


Updated to:
Doc. No.TypeCitationLinkEmailOther DetailsAttachment
23462Study protocol-999999  
23463Informed consent form-999999  

Results publications and other study-related documents

Documents added manually
Current Study Results
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Update to Study Results
Doc. No.TypeIs Peer Reviewed?DOICitations or Other DetailsAttachment
4033Plain language summaryNo Context: Establishment of the infant gut microbiom... [More Details]

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