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Trial registered on ANZCTR


Registration number
ACTRN12615001075572
Ethics application status
Approved
Date submitted
18/09/2015
Date registered
13/10/2015
Date last updated
11/03/2019
Date data sharing statement initially provided
11/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Investigating the effect of maternal prebiotic fibre supplementation during pregnancy and breastfeeding on the prevention of early childhood allergies.
Scientific title
A randomised, double-blind, placebo-controlled trial to investigate the effects of maternal dietary prebiotic fibre supplementation, from early pregnancy to 6 months lactation, on infant outcomes of immune function and eczema diagnosis.
Secondary ID [1] 287216 0
Nil
Universal Trial Number (UTN)
Trial acronym
SYMBA Study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Allergic Disease 295810 0
Condition category
Condition code
Inflammatory and Immune System 296072 296072 0 0
Allergies
Oral and Gastrointestinal 296527 296527 0 0
Normal oral and gastrointestinal development and function

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
2 scoops of study powder containing 9g prebiotics (scGOS/IcFOS 9:1 ratio) will be mixed with food or beverage and consumed orally once daily by the participating pregnant women from study entry (18-20 weeks gestation) until 6 months of lactation. Compliance with the intervention will be assessed by questions asked at regular phone calls and appointment visits during the intervention period. The participating women will also be asked to return any unused study powder tins for reweighing as another measure of compliance at the end of the intervention period.
Intervention code [1] 292502 0
Prevention
Comparator / control treatment
2 scoops of study powder containing 8g of maltodextrin powder will be mixed with food or beverage and consumed orally once daily by the participating pregnant women from study entry (18-20 weeks gestation) until 6 months of lactation. Compliance with the intervention will be assessed by questions asked at regular phone calls and appointment visits during the intervention period. The participating women will also be asked to return any unused study powder tins for reweighing as another measure of compliance at the end of the intervention period.
Control group
Placebo

Outcomes
Primary outcome [1] 295748 0
Immune studies will be performed using mononuclear cells from a blood sample on 120 infants at 6 months of age. We will assess the effect of the intervention on a composite outcome incorporating: innate immune responses to microbial products, including inflammatory cytokine (IL-6, TNF alpha, IL-1 beta, IL-12 and IL-10) responses to a range of toll-like receptor ligands; effector T cell responses to mitogens and allergens including Th2 (IL-13, IL-5), Th1 (IFN-gamma) and IL-10 responses in the supernatants; regulatory T cell responses including the numbers and function of CD4+C25+CD127 cells and expression of regulatory marker FOXP3+.

Timepoint [1] 295748 0
At 6 months of age in the infant.
Primary outcome [2] 295749 0
In this composite primary outcome, infant stool samples will be analysed for eosinophilic cationic protein (ECP) and secretory immunoglobulin A (sIgA), as measures of local gut inflammation and immune function.
Timepoint [2] 295749 0
At 6 months of age in the infant.
Secondary outcome [1] 316400 0
In this composite secondary outcome, the development of allergic disease (eczema and/or food allergy) in the infant, will be determined by completion of interview-administered questions and the infant will be examined for signs of allergic disease.
Timepoint [1] 316400 0
At 3, 6 and 12 months of age of the infant.
Secondary outcome [2] 316401 0
In this composite secondary outcome, the child's sensitisation to food and/or aeroallergens will be assessed by allergy skin prick testing (SPT) with histamine and control solutions in accordance with standard clinical methods as outlined in the 2009 ASCIA Skin Prick Testing for the Diagnosis of Allergic Disease: A manual for practitioners.
Timepoint [2] 316401 0
At 12 months of age of the infant.

Eligibility
Key inclusion criteria
Pregnant women less than 21 weeks of gestation, whose infants have a first-degree relative (mother, father or sibling) with a history of medically diagnosed allergic disease (asthma, allergic rhinitis, eczema and/or food allergy). Eligibility is not dependent on intent to breastfeed for a given length of time.
Minimum age
18 Years
Maximum age
50 Years
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Maternal smoking during pregnancy.
Women already regularly consuming prebiotic supplement (more than twice a week).
Current maternal diagnosis of lactose intolerance or cows milk allergy or other significant chronic gastrointestinal condition.

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)
Written informed consent will be obtained before participating in an enrolment appointment. Each participating pregnant woman will be assigned a unique study number and randomly allocated (computer generated) into one of two intervention groups.
The allocation will be concealed be central randomisation using a computer system.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The randomisation schedule will be computer-generated (varying size of permuted blocks), and stratified by maternal allergy status and body mass index (BMI). The randomisation schedule will be produced by an independent party.
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
We can detect differences in aspects of immune function in studies of this size or smaller, including differences in cytokine detection in our previous intervention studies using probiotics in pregnancy. Although no specific sample size calculations were done for the composite primary outcome for this trial, the subgroup of 120 (60 per group) infant blood samples at 6 months of age that will be selected for immunological studies will be sufficient to detect biologically relevant differences in proposed immune outcomes. This is based on our extensive experience with similar populations.
All analyses will be on an intention-to-treat basis.
For the biological analysis: continuous variables (e.g. cytokines) will be compared between groups with linear regression models (transformation of the outcome variable will be employed as required to meet the assumptions of the linear regression model) to allow for adjustment of confounders. Binary variables will be compared using logistic regression to allow for adjustment of relevant prognostic baseline variables and confounding post-randomisation interactions.

For the clinical analysis, the proportion of children with diagnosed allergic disease at 12 months of age will be compared between treatment groups using an identity binomial generalized linear model, adjusting for the pre-specified prognostic stratification variables. Differences in secondary clinical outcomes will be examined in the same way.

Recruitment
Recruitment status
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 in Australia
Recruitment state(s)
WA
Recruitment hospital [1] 4134 0
Joondalup Health Campus - Joondalup
Recruitment postcode(s) [1] 10065 0
6027 - Joondalup

Funding & Sponsors
Funding source category [1] 291791 0
Government body
Name [1] 291791 0
Telethon-Perth Children’s Hospital Research Fund Department of Health of Western Australia
Address [1] 291791 0
Department of Health of Western Australia
PO Box 8172
Perth Business Centre
WA 6849
Country [1] 291791 0
Australia
Funding source category [2] 293652 0
Government body
Name [2] 293652 0
National Health and Medical Research Council
Address [2] 293652 0
GPO Box 9848 Canberra ACT 2601
Country [2] 293652 0
Australia
Primary sponsor type
Other
Name
Telethon Kids Institute
Address
100 Roberts Road
Subiaco, 6008
Western Australia

Country
Australia
Secondary sponsor category [1] 290627 0
None
Name [1] 290627 0
Address [1] 290627 0
Country [1] 290627 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 293459 0
Joondalup Health Campus Human Research Ethics Committee
Ethics committee address [1] 293459 0
Grand Blvd & Shenton Avenue
Joondalup, 6026
WA
Ethics committee country [1] 293459 0
Australia
Date submitted for ethics approval [1] 293459 0
05/11/2014
Approval date [1] 293459 0
02/02/2016
Ethics approval number [1] 293459 0
1541r

Summary
Brief summary
This project will recruit pregnant women to receive either a prebiotic supplement or a placebo supplement. They will be asked to take the supplement from 18-20 weeks gestation until their baby is 6 months of age. We will then examine whether supplementing the mother’s diet during pregnancy and breastfeeding with the prebiotic powder will reduce the development of allergies in her child. Both study groups will include children deemed to be at high risk of allergic disease (based on family allergy history).
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 59314 0
Prof Susan Prescott
Address 59314 0
Telethon Kids Institute
100 Roberts Road
Subiaco WA 6008
Country 59314 0
Australia
Phone 59314 0
+61 8 9489 7714
Fax 59314 0
Email 59314 0
susan.prescott@telethonkids.org.au
Contact person for public queries
Name 59315 0
Dr Debra Palmer
Address 59315 0
Childhood Allergy and Immunology Research, Level 7, Telethon Kids Institute, Perth Children's Hospital, 15 Hospital Ave, Nedlands WA 6009
Country 59315 0
Australia
Phone 59315 0
+61 8 6319 1750
Fax 59315 0
Email 59315 0
debbie.palmer@telethonkids.org.au
Contact person for scientific queries
Name 59316 0
Dr Debra Palmer
Address 59316 0
Childhood Allergy and Immunology Research, Level 7, Telethon Kids Institute, Perth Children's Hospital, 15 Hospital Ave, Nedlands WA 6009
Country 59316 0
Australia
Phone 59316 0
+61 8 6319 1750
Fax 59316 0
Email 59316 0
debbie.palmer@telethonkids.org.au

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
Yes
What data in particular will be shared?
After de-identification, individual participant data underlying published results only.
When will data be available (start and end dates)?
Beginning 6 months and ending 5 years following main results publication.
Available to whom?
Case-by-case basis at the discretion of CIs Susan Prescott and Debra Palmer
Available for what types of analyses?
For IPD meta-analyses
How or where can data be obtained?
Access subject to approvals by CIs Susan Prescott and Debra Palmer
What supporting documents are/will be available?
No other documents available
Summary results
No Results