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Trial registered on ANZCTR


Registration number
ACTRN12617001465347
Ethics application status
Approved
Date submitted
5/10/2017
Date registered
17/10/2017
Date last updated
21/02/2020
Date data sharing statement initially provided
11/03/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Breastfeeding and Eating Nuts and Eggs For Infant Tolerance (BENEFIT) Trial
Scientific title
Breastfeeding and Eating Nuts and Eggs For Infant Tolerance (BENEFIT) Trial
Secondary ID [1] 293070 0
Nil known
Universal Trial Number (UTN)
Trial acronym
BENEFIT Trial
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Food Allergy 305004 0
Condition category
Condition code
Inflammatory and Immune System 304325 304325 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
The maternal diet rich in eggs and peanuts intervention group: Regular maternal consumption of 6 eggs and 60 peanuts (= 2 handfuls) per week from birth until 6 months infant age.
Participating women will be able to include all forms of egg and peanut, and egg and peanut containing foods, towards their weekly target of egg and peanut ingestion. They will be provided with a conversion table showing the amount present in common egg or peanut foods, for example peanut butter, or egg in quiche, or in baked goods.
Both groups of women will be provided with a supply of both peanuts and peanut butter to reduce costs of participation in this trial and to assist with intervention compliance. Due to the reduced shelf-life of eggs these will need to be purchased by the participants themselves.
Compliance: Participants will be in contact with the research team each month during the intervention period, either via a telephone call (at 1, 2 and 5 months of infant age) or in person at an appointment (at 3-4 and 6 months of infant age). During these contact time points the participants will be asked to recall their dietary intake of egg and peanut containing foods over the preceding week and this information will be used to assess intervention compliance. Comprehensive breastfeeding data will also be collected during these contact time points. The intervention group dietary advice will be given by the recruitment research assistant who will also collect dietary compliance data, but not collect any outcome assessment data. Our experience has found that monthly participant contact throughout the intervention period maximises compliance and follow-up.
Intervention code [1] 299312 0
Prevention
Comparator / control treatment
The maternal diet low in eggs and peanuts control group: Maternal consumption of up to 2 eggs and up to 20 peanuts per week from birth until 6 months infant age.
Participating women will be able to include all forms of egg and peanut, and egg and peanut containing foods, towards their weekly target of egg and peanut ingestion. They will be provided with a conversion table showing the amount present in common egg or peanut foods, for example peanut butter, or egg in quiche, or in baked goods.
Both groups of women will be provided with a supply of both peanuts and peanut butter to reduce costs of participation in this trial and to assist with intervention compliance. Due to the reduced shelf-life of eggs these will need to be purchased by the participants themselves.
Compliance: Participants will be in contact with the research team each month during the intervention period, either via a telephone call (at 1, 2 and 5 months of infant age) or in person at an appointment (at 3-4 and 6 months of infant age). During these contact time points the participants will be asked to recall their dietary intake of egg and peanut containing foods over the preceding week and this information will be used to assess intervention compliance. Comprehensive breastfeeding data will also be collected during these contact time points. The intervention group dietary advice will be given by the recruitment research assistant who will also collect dietary compliance data, but not collect any outcome assessment data. Our experience has found that monthly participant contact throughout the intervention period maximises compliance and follow-up.
Control group
Dose comparison

Outcomes
Primary outcome [1] 303588 0
Egg-specific IgG4 concentrations in infant blood. These will be measured using the ImmunoCAP 250 system (Phadia AB, Uppsala, Sweden).
Timepoint [1] 303588 0
When Infant is 6 months of age.
Primary outcome [2] 303653 0
Peanut-specific IgG4 concentrations in infant blood. These will be measured using the ImmunoCAP 250 system (Phadia AB, Uppsala, Sweden).
Timepoint [2] 303653 0
When infant is 6 months of age.
Secondary outcome [1] 339503 0
Sensitization to egg measured by egg-specific IgE concentrations levels in infant blood. These will be measured using the ImmunoCAP 250 system (Phadia AB, Uppsala, Sweden).
Timepoint [1] 339503 0
When infant is 3-4 months of age.
Secondary outcome [2] 339505 0
Medically diagnosed infant food allergy to egg after solids introduction of egg before 9 months of age via data linkage to patient medical records.
Timepoint [2] 339505 0
When Infant is 9 months of age.
Secondary outcome [3] 339506 0
Medically diagnosed infant eczema before 9 months of age via parent self-report.
Timepoint [3] 339506 0
When Infant is 9 months of age.
Secondary outcome [4] 339508 0
Egg-specific IgG4 concentrations in infant blood. These will be measured using the ImmunoCAP 250 system (Phadia AB, Uppsala, Sweden).
Timepoint [4] 339508 0
When the infant is 3-4 months of age.
Secondary outcome [5] 339756 0
Sensitization to peanut measured by peanut-specific IgE concentrations levels in infant blood. These will be measured using the ImmunoCAP 250 system (Phadia AB, Uppsala, Sweden).
Timepoint [5] 339756 0
When infant is 3-4 months of age.
Secondary outcome [6] 339757 0
Sensitization to peanut measured by peanut-specific IgE concentrations levels in infant blood. These will be measured using the ImmunoCAP 250 system (Phadia AB, Uppsala, Sweden).
Timepoint [6] 339757 0
When infant is 6 months of age.
Secondary outcome [7] 339758 0
Sensitization to egg measured by egg-specific IgE concentrations levels in infant blood. These will be measured using the ImmunoCAP 250 system (Phadia AB, Uppsala, Sweden).
Timepoint [7] 339758 0
When the infant is 6 months of age.
Secondary outcome [8] 339759 0
Medically diagnosed infant food allergy to peanut after solids introduction of peanut before 9 months of age via data linkage to patient medical records.
Timepoint [8] 339759 0
When infant is 9 months of age.
Secondary outcome [9] 339760 0
Medically diagnosed infant wheeze before 9 months of age via parent self-report.
Timepoint [9] 339760 0
When infant is 9 months of age.
Secondary outcome [10] 339761 0
Peanut-specific IgG4 concentrations in infant blood. These will be measured using the ImmunoCAP 250 system (Phadia AB, Uppsala, Sweden).
Timepoint [10] 339761 0
When the infant is 3-4 months of age.

Eligibility
Key inclusion criteria
Eligible participants will be women who are planning to breastfeed for at least 6 months. Infants to have at least two family members (mother, father or siblings) with medically diagnosed allergic disease (asthma, eczema, hay-fever or IgE mediated food allergy).
Minimum age
18 Years
Maximum age
No limit
Gender
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
Women with egg or peanut allergies (<1% of adult population) will be excluded, as they would be unable to safely follow the intervention without an allergic reaction.

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)
Allocation was concealed via a central randomisation by computer.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software (i.e. computerised sequence generation).
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?


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
Analysis Plan: For outcome measurements with detection thresholds, for example IgG4 concentrations, Tobit regression models will be used, with treatment effects described using ratios of means and 95% confidence intervals. The secondary binary outcomes food allergy, eczema and wheeze will be analysed using log binomial regression models, with treatment effects described using relative risks and 95% confidence intervals.
Sample size calculations: The primary outcome for this study will be egg and peanut-specific IgG4 antibody levels. The expected prevalence of detectable egg and peanut-specific IgG4 concentrations in the intervention group is 88% compared to the control group 22%. For 90% power and 95% confidence (alpha-value 0.05), we require 22 mother-infant pairs per group. To allow for up to 30% ceasing breastfeeding prior to 6 months of age and a blood collection rate of 50% on the infants, we will recruit a total of 108 participants (mother-infant pairs).

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] 9161 0
Joondalup Health Campus - Joondalup
Recruitment postcode(s) [1] 17674 0
6027 - Joondalup

Funding & Sponsors
Funding source category [1] 297691 0
Charities/Societies/Foundations
Name [1] 297691 0
Foundation for Children
Address [1] 297691 0
GPO Box 3655
Sydney NSW 2001
Country [1] 297691 0
Australia
Funding source category [2] 297694 0
Government body
Name [2] 297694 0
Telethon-Perth Children’s Hospital Research Fund
Address [2] 297694 0
Research Development Unit
Department of Health
PO Box 8172
Perth Business Centre
PERTH WA 6849
Country [2] 297694 0
Australia
Primary sponsor type
University
Name
University of Western Australia
Address
35 Stirling Highway
Crawley WA 6009
Country
Australia
Secondary sponsor category [1] 296714 0
None
Name [1] 296714 0
Address [1] 296714 0
Country [1] 296714 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298764 0
Joondalup Health Campus
Ethics committee address [1] 298764 0
Cnr Grand Blvd and Shenton Ave, Joondalup, WA 6027
Ethics committee country [1] 298764 0
Australia
Date submitted for ethics approval [1] 298764 0
29/08/2017
Approval date [1] 298764 0
22/09/2017
Ethics approval number [1] 298764 0
1729

Summary
Brief summary
Regular consumption of traditionally allergenic foods, like egg and peanut, in solid foods can reduce food allergies, however this is too late for some infants. We have discovered that infant immune responses to egg can be beneficially enhanced during the first six weeks of breastfeeding when mothers eat more eggs. We now propose to investigate the effects of breastfeeding mothers eating higher dietary intakes of both egg and peanut for an extended period of the first six months of life. The key translatable message from this project will be to answer the question of whether higher maternal dietary intakes of eggs and peanuts during breastfeeding are needed to reduce the risk of food allergy development.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 78154 0
Dr Debbie Palmer
Address 78154 0
Level 7, Telethon Kids Institute, Perth Children's Hospital, 15 Hospital Ave Nedlands WA 6009
Country 78154 0
Australia
Phone 78154 0
+61 410 851 607
Fax 78154 0
Email 78154 0
debbie.palmer@telethonkids.org.au
Contact person for public queries
Name 78155 0
Dr Debbie Palmer
Address 78155 0
Level 7, Telethon Kids Institute, Perth Children's Hospital, 15 Hospital Ave Nedlands WA 6009
Country 78155 0
Australia
Phone 78155 0
+61 410 851 607
Fax 78155 0
Email 78155 0
debbie.palmer@telethonkids.org.au
Contact person for scientific queries
Name 78156 0
Dr Debbie Palmer
Address 78156 0
Level 7, Telethon Kids Institute, Perth Children's Hospital, 15 Hospital Ave Nedlands WA 6009
Country 78156 0
Australia
Phone 78156 0
+61 410 851 607
Fax 78156 0
Email 78156 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 after and ending 5 years following main results publication.
Available to whom?
Case by case basis at the discretion of CI Debbie Palmer
Available for what types of analyses?
For IPD meta-analyses.
How or where can data be obtained?
Access subject to approvals by CI Debbie Palmer
What supporting documents are/will be available?
No other documents available
Summary results
No Results