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Trial registered on ANZCTR


Registration number
ACTRN12617001604392
Ethics application status
Approved
Date submitted
22/08/2017
Date registered
7/12/2017
Date last updated
5/08/2021
Date data sharing statement initially provided
10/12/2018
Date results information initially provided
5/08/2021
Type of registration
Retrospectively registered

Titles & IDs
Public title
Can probiotics reduce the severity of food allergies?
Scientific title
Feasibility Study – Probiotics and Repeat Food Challenge
in Food Allergic Children
Secondary ID [1] 292708 0
nil
Universal Trial Number (UTN)
U1111-1181-9126
Trial acronym
PROFOOD
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Food Allergy 304468 0
Condition category
Condition code
Inflammatory and Immune System 303805 303805 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
A pilot double-blind randomised placebo-controlled trial of the capacity of an established probiotic, Lactobacillus rhamnosus HN001, to enhance food tolerance in children diagnosed with IgE-mediated food allergy who have been referred by their paediatrician at Capital and Coast District Health Board (CCDHB) to undergo an open oral food challenge.

Children will receive a capsule (either whole or contents sprinkled on food) containing HN001 at a dose of 9.2 x 10^9 CFU daily (or placebo) for three months, started immediately after the food challenge.

Participants will be instructed to keep the capsule bottle (even if empty) containing unused capsules for return to study staff. At the repeat food challenge appointment, the study nurse will collect the capsule bottle with the remaining capsules, if any, from the participant and store these in the walk-in fridge at Wellington Asthma Research Group,. As a check on compliance, these will be counted and numbers recorded in the ProFood Study database. This will be done only at the end of the study as it is important that all researchers involved in seeing participants remain blind.

If a participant loses a capsule bottle, research staff should ask for an estimate of how many capsules had been taken when it was lost. When entering this into the ProFood Study database, we will estimate the number remaining by subtracting the estimated number taken from 105 and ticking the box to show it was an estimate.

If a participant forgets to bring the remaining capsules to the end of study visit, the research staff will give them a pre-paid, self-addressed envelope to post the capsule bottle back to School of Medicine.

Children will be randomised to active or placebo groups as described. Those randomised to control will provide useful information as to the reliability of food challenges when repeated after approx 3 months, and also information on the natural time course of rising levels of calprotectin and/or faecal esterase [if seen] after a food challenge and comparisons between these two markers of gut inflammation. Those not eligible to take part in the study (either nearly fully tolerant of the food or so sensitive we would not consider re-challenge) can still elect to collect their infant's stools to provide further information on the natural history of faecal calprotectin and leucocyte esterase after a markedly positive or negative food challenge. Faecal collection times would be as per those children enrolled.
Intervention code [1] 298949 0
Treatment: Other
Comparator / control treatment
The placebo capsules contain powder which is is corn-derived maltodextrin, manufactured by Grain Processing Corp. Oregan, USA
Control group
Placebo

Outcomes
Primary outcome [1] 303166 0
The primary outcome measure is the stage in the food challenge at which the child is deemed to have failed according to the CCDHB food challenge protocol.
Timepoint [1] 303166 0
Repeat food challenge three months after commencement of the intervention.
Primary outcome [2] 303386 0
The acceptability of performing a repeat food challenge on children within 3 months of the first. This will be ascertained at the end of the study when we will know how many children were eligible to receive the intervention and undergo the repeat food challenge but elected not to do so, and how many received the intervention but decided not to undergo the repeat food challenge. We will report acceptability as a proportion.
Timepoint [2] 303386 0
At the end of the study.
Primary outcome [3] 303387 0
The willingness of parents to collect serial stool samples from their children. This will be ascertained at the end of the study when we will know how many parents were invited to collect stool samples but did not agree to, and how many agreed to but did not manage to do so. We will report willingness as a proportion.
Timepoint [3] 303387 0
At the end of the study.
Secondary outcome [1] 338089 0
Levels of faecal calprotectin and faecal leukocyte esterase in children receiving the intervention and those allocated to the placebo arm.
Timepoint [1] 338089 0
At baseline and 2, 5, 7 and 30 days after the first oral food challenge and and 2 days prior to the repeat oral challenge.
Secondary outcome [2] 338281 0
Levels of faecal esterase in children not receiving the intervention and those allocated to the placebo arm.
Timepoint [2] 338281 0
baseline, 2, 5, 7 and 30 days after the first oral food challenge

Eligibility
Key inclusion criteria
children who are aged less than 16 years and have IgE-mediated food allergy with evidence of allergic sensitisation; and have failed steps 2, 3, or 4 (out of 5) of the first food challenge.
Minimum age
No limit
Maximum age
16 Years
Gender
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
children who:
• will not be living in Wellington over the next 4 months
• are currently using or intend to use probiotic drinks or supplements
• are participating in another health-related research study involving an intervention
• have a severe disorder such as kidney failure, cystic fibrosis, severe heart disease, or
inflammatory bowel disease:
• are on long-term or continuous antibiotic therapy
• have cardiac valve disease where antibiotic prophylaxis is required
• have a serious immunological disorder that suppresses immune function
• are taking immunosuppressant drugs.

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)
Co-sponsor (Fonterra Ltd NZ) will randomize and code opaque bottles of capsules with the study number. Capsules will be couriered to Wellington and each bottle will contain 105 capsules (3 months’ supply plus 2 weeks extra). The investigators and participants will be blind to the randomisation process.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
The ProFood Study database will have a series of registration numbers (starting with “R” followed by three digits e.g. R001 – R999). When the clinic nurse calls a parent to make the food challenge appointment, they will fill out a registration form for the child and assign a registration number to the child.

The ProFood Study database will have a series of study numbers made up of 3 three-digit components eg xxx-xxx-xxx. The first 3 digits relate to whether the participant has provided a baseline faecal sample; the second 3 digits relate to whether the participant is taking part in the probiotics and repeat food challenge part of the study; and the third 3 digit relates to whether the participant is providing post-challenge faecal samples. Each set of digits will run from 001 to 999. Each set of digits will be assigned consecutively and ticked off in the database when it is assigned.
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
Patients who do not meet inclusion criteria for the intervention ( either no or mild reactions to food ( no reaction to step 4)) or who have severe sensitivity (react to step 1) will be invited to collect sequential stool samples as above for calprotectin and leucocyte esterase levels if they are willing, so as to expand experience with these tests.
Phase
Not Applicable
Type of endpoint(s)
Efficacy
Statistical methods / analysis
We plan to enrol 60 children: 30 in each study group. This sample size will provide 80% power to detect a difference between 5% of children improving in the placebo group and 33% of children improving in the treatment group.

Data analysis: The quantity of interest is the difference between the proportion of children who would improve in the treatment population and the proportion who would improve in the control population. Individual upper and lower 95% confidence limits will be calculated for this difference in proportions. This procedure estimates the quantity of interest, and it also acts as a one-tailed test of the null hypothesis of no benefit at the 0.05 level.

Recruitment
Recruitment status
Stopped early
Data analysis
Data collected is being analysed
Reason for early stopping/withdrawal
Lack of funding/staff/facilities
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] 9158 0
New Zealand
State/province [1] 9158 0
Wellington

Funding & Sponsors
Funding source category [1] 297346 0
University
Name [1] 297346 0
university of otago research grant
Address [1] 297346 0
Otago University Wellington PO box 7343 Wellington South 6242
Country [1] 297346 0
New Zealand
Funding source category [2] 297351 0
Commercial sector/Industry
Name [2] 297351 0
Fonterra NZ Ltd
Address [2] 297351 0
Fonterra Co-operative Group Limited
109 Fanshawe Street
Auckland 1010
New Zealand
Country [2] 297351 0
New Zealand
Primary sponsor type
Individual
Name
Thorsten V Stanley
Address
Dept of Paediatrics University of Otago Wellington PO BOX 7343 Wellington South
Country
New Zealand
Secondary sponsor category [1] 296325 0
Individual
Name [1] 296325 0
Janice Kang
Address [1] 296325 0
Dept of Medicine University of Otago Wellington PO BOX 7343 Wellington South
Country [1] 296325 0
New Zealand

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 298446 0
NZ Northern B Region Ethics Committee
Ethics committee address [1] 298446 0
Ministry of Health
Health and Disability Ethics Committees
PO Box 5013
Wellington 6140
Ethics committee country [1] 298446 0
New Zealand
Date submitted for ethics approval [1] 298446 0
01/09/2016
Approval date [1] 298446 0
30/11/2016
Ethics approval number [1] 298446 0
16/NTB/184

Summary
Brief summary
We plan to undertake a feasibility study in children who have IgE-mediated allergy to foods previously proven by food challenge. The study aims to demonstrate improved tolerance to food by retesting reactions to food after receiving 3 months of daily probiotic supplementation with L.rhamnosus HN001. We hypothesize that HN001 will improve the children’s tolerance to foods by moderating their immune response, as demonstrated in other studies. The results of this pilot study will inform the design of a larger fully-powered randomized control trial (RCT) to examine the efficacy and mechanism of action of this probiotic in improving food tolerance in food allergy. We will collect stools from children before/after the food challenge to see if either of two markers of bowel inflammation may assist in diagnosing IgE-mediated food allergy
Trial website
Trial related presentations / publications
Public notes
target size (60) is for the intervention study only. Parents of children not eligible for the intervention study may still elect to collect sequential faecal samples for the study of gut inflammation after a food challenge part of the study. We do not know how many this will be but due to funds available we will limit this to a maximum 20 further children not taking part in the intervention.

Contacts
Principal investigator
Name 77122 0
Dr Thorsten Villiers Stanley
Address 77122 0
Dept of Paediatrics
University of Otago Wellington
PO Box 7343 Wellington South NZ
Country 77122 0
New Zealand
Phone 77122 0
+6443855999
Fax 77122 0
+6443855898
Email 77122 0
thorsten.stanley@otago.ac.nz
Contact person for public queries
Name 77123 0
Dr Thorsten Villiers Stanley
Address 77123 0
Dept of Paediatrics University of Otago Wellington
Wellington Hospital
PO BOX 7343 Wellington South
Country 77123 0
New Zealand
Phone 77123 0
+6443855999
Fax 77123 0
+6443855898
Email 77123 0
thorsten.stanley@otago.ac.nz
Contact person for scientific queries
Name 77124 0
Dr Thorsten Villiers Stanley
Address 77124 0
Dept of Paediatrics University of Otago Wellington
Wellington Hospital
PO BOX 7343 Wellington South
Country 77124 0
New Zealand
Phone 77124 0
+64212436632
Fax 77124 0
+6443855898
Email 77124 0
thorsten.stanley@otago.ac.nz

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
We have not sought permission from our participants to share their data.
What supporting documents are/will be available?
No other documents available
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary