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Trial registered on ANZCTR


Registration number
ACTRN12619001674123
Ethics application status
Approved
Date submitted
30/10/2019
Date registered
29/11/2019
Date last updated
29/11/2019
Date data sharing statement initially provided
29/11/2019
Type of registration
Prospectively registered

Titles & IDs
Public title
Maintaining regular peanut ingestion after peanut oral immunotherapy in children
Scientific title
Optimizing treatment adherence and supporting ongoing desensitization following peanut oral immunotherapy in children: a randomized controlled trial of daily versus weekly peanut ingestion
Secondary ID [1] 299674 0
None
Universal Trial Number (UTN)
Trial acronym
Post-HYPES
Linked study record
ACTRN12617000803392 (Trial Acronym ‘HYPES’), the goal of which was to determine the safety and efficacy of a sequential peanut oral immunotherapy regimen utilizing boiled and then roasted peanuts in a triple-phase study design. Post-HYPES is a follow-up study on those peanut-allergic children who have been successfully desensitized.

Health condition
Health condition(s) or problem(s) studied:
Peanut allergy 315019 0
Condition category
Condition code
Inflammatory and Immune System 313353 313353 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
In the previous HYPES study (see ACTRN12617000803392), children aged 6-18 with a clear positive history of peanut allergy and a SPT equal or greater than 8 mm, or psIgE equal or greater than 15 kU/L were treated with a 3-step desensitisation protocol as described in the clinical trial registration. To date, 56 subjects have completed the oral immunotherapy protocol, and all have passed the exit oral food challenge test (witnessed ingestion of 12 roasted peanuts or 3000 mg of peanut protein) after a minimum of 12 months treatment. Following successful desensitisation, subjects were invited to participate in this follow-up study, in which they would be randomised into 2 groups for ongoing ingestion of roasted peanuts as maintenance. One group would be ingesting at least 2 roasted peanuts daily while the second group would be ingesting at least 14 peanuts all on one day once a week.

We anticipate that some children might dislike the taste of peanuts while others might actually like to eat more or to try some other peanut products, so we have stratified the participants into “like” and “dislike” before randomizing each group. Children who liked peanuts would be allowed to consume ad libitum additional peanuts or peanut protein in other foods such as peanut butter/paste.

Participants will be followed up for 12 months with 3 interviews: at base-line, mid-term (6 months) and exit (12 months), during which they would have skin prick tests, blood taken for psIgE, psIgG4, or any other relevant parameters, and a set of 7 psychological questionnaires evaluating stress, anxiety, depression, burden and quality of life, in both children and their parents.

For those subjects randomised to ingest peanuts once a week, a special schedule of 3 months was designed to allow gradually transition from daily ingestion of 12 roasted peanuts to once weekly ingestion of 14 roasted peanuts, as follows:

1. Immediately after enrolment, subjects in Group B will increase their daily ingestion of peanuts from 12 per day to 14 per day over a 2 week period. They will then enter a transition phase, taking approximately 3 months to achieve:
2. Ingest peanuts every second day: on Day 1, 3, 5.
3. Ingest every third day: on Day 8, 11, 14.
4. Ingest every fourth day, on Day 18, 22, 26.
5. Ingest every fifth day, on Day 31, 36, 41.
6. Ingest every 6th day, on Day 47, 53, 59.
7. From Day 66 onwards: ingest once a week for the remaining treatment period of 12 months.
8. Patients are assessed at 3 months to see if the transition is successful.

For those randomised to ingest peanuts daily, they would simply reduce their peanut intake from 12 peanuts daily to 2 peanuts daily.

At the end of 12 months, all subjects will have a witnessed oral food challenge to confirm that they have successfully maintained their desensitised status.

Subjects who consent to the study but refuse randomisation will be invited to answer the questionnaires at baseline and 12 months after desensitisation. Some of them might still be ingesting peanuts regularly, at their own choice but probably less disciplined than subjects in the formal randomised trial, or might have given up ingesting peanuts regularly altogether. We believe the psychological data from this sub-group of subjects could be very valuable, when compared with the more disciplined per-protocol participants.

The following are the list of 7 questionnaires:

Children:
o Quality of life Peanut allergy PedQL
o Revised Children’s Anxiety and Depression Scale (RCADS)
o Perceived Stress Scale for Children (PSSC)

Parents:
o Food Quality of Life Parent Form
o Food Allergy Quality of Life Parental Burden Scale
o Depression, Anxiety and Stress Scale (DASS)
o Perceived Stress Scale (PSS)
Intervention code [1] 315939 0
Prevention
Intervention code [2] 316085 0
Treatment: Other
Intervention code [3] 316086 0
Behaviour
Comparator / control treatment
We are comparing ingestion of 2 peanuts daily, versus ingesting 14 peanuts once a week. The comparator group is daily ingestion of peanuts.
Control group
Active

Outcomes
Primary outcome [1] 321832 0
Ongoing desensitization to peanut, as determined by successful completion of oral food challenge
Timepoint [1] 321832 0
12 months post intervention commencement.
Secondary outcome [1] 376394 0
Adverse events recorded during 12-month maintenance including urticaria (localised or generalised), angioedema, rhinitis, conjunctivitis, respiratory symptoms (cough, wheeze), vomiting, diarrhoea, anaphylaxis). These will be patient self-reported using a log book completed by the participants. Participant administered medication including Epipen will also be recorded. Any medical attendance related to the adverse events will be recorded by the participant, supported by further communication with the treating clinician.
Timepoint [1] 376394 0
Every 3 months post treatment commencement for 12 months
Secondary outcome [2] 376395 0
Skin prick tests to follow the progress of peanut allergy status in participants
Timepoint [2] 376395 0
0, 6 and 12 months post intervention commencement
Secondary outcome [3] 376396 0
Impact of maintaining desensitisation on parental quality of life as assessed by Food Quality of Life Parent Form and Food Quality of Life Parental Burden Scale questionnaires.
Timepoint [3] 376396 0
0, 6 and 12 months post intervention commencement
Secondary outcome [4] 376398 0
Impact of maintaining desensitisation on parental depression as assessed by Depression, Anxiety and Stress Scale questionnaire.
Timepoint [4] 376398 0
0, 6 and 12 months post intervention commencement
Secondary outcome [5] 376904 0
Impact of maintaining desensitisation on parental anxiety, as assessed by Depression, Anxiety and Stress Scale questionnaire.
Timepoint [5] 376904 0
0, 6 and 12 months post intervention commencement
Secondary outcome [6] 376905 0
Impact of maintaining desensitisation on parental stress, as assessed by Depression, Anxiety and Stress Scale, and Perceived Stress Scale questionnaires.
Timepoint [6] 376905 0
0, 6 and 12 months post intervention commencement
Secondary outcome [7] 376906 0
Impact of maintaining desensitisation on child quality of life as assessed by Peanut Allergy Quality of Life questionnaire.
Timepoint [7] 376906 0
0, 6 and 12 months post intervention commencement
Secondary outcome [8] 377265 0
Impact of maintaining desensitisation on child depression as assessed by Revised Children's Anxiety and Depression Scale questionnaire.
Timepoint [8] 377265 0
0, 6 and 12 months post intervention commencement
Secondary outcome [9] 377266 0
Impact of maintaining desensitisation on child anxiety, as assessed by Revised Children's Anxiety and Depression Scale questionnaire.
Timepoint [9] 377266 0
0, 6 and 12 months post intervention commencement
Secondary outcome [10] 377267 0
Impact of maintaining desensitisation on child stress, as assessed by Perceived Stress Scale for Children questionnaire.
Timepoint [10] 377267 0
0, 6 and 12 months post intervention commencement
Secondary outcome [11] 377271 0
Adherence based on self report of peanut consumption over the preceding 14 days at each assessment time point.
Timepoint [11] 377271 0
Every 3 months post treatment commencement
Secondary outcome [12] 377272 0
Peanut specific IgE using serum immunoassay
Timepoint [12] 377272 0
0, 6 and 12 months post intervention commencement
Secondary outcome [13] 377278 0
Peanut specific IgG4 levels using serum immunoassay
Timepoint [13] 377278 0
0, 6 and 12 months post intervention commencement

Eligibility
Key inclusion criteria
Children and the parents of children who have (1) completed the HYPES study, (2) passed the exit oral food challenge of the HYPES study,
Minimum age
7 Years
Maximum age
80 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
Children and parents of children who had withdrawn or did not complete HYPES study (and passing the exit oral food challenge) - excluded because they were not successfully desensitized.

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)
Treatment will be assigned using concealed in opaque envelopes.
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Treatment will be assigned with the help of a computer-generated randomization schedule,
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Parallel
Other design features
Parents and children who refuse to be randomized because they want to choose their own way of maintaining peanut ingestion will still be able to consent for follow up to answer the questionnaires and contribute to the understanding of psychological issues and quality of life in children after peanut desensitization,
Phase
Not Applicable
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Analysis will be undertaken according to intention-to-treat principle. Dichotomous outcomes, including successful completion of oral food challenges, risk and frequency of participants experiencing adverse effects, and adequate treatment adherence, will be assessed by calculating a risk ratio (RR) with 95% CI, determined with a log-binomial model. Food related QoL at end of trial will be compared between-groups using linear-mixed models, adjusting for food related QoL. Appropriate statistical analyses for immunological measurements will be undertaken according to underlying distribution of each variable (i.e. IgE, IgG4, skin pricks). Differences between-groups at baseline, 6 months and 12 months will be compared using Two Sample t-Test or Wilcoxon Rank Sum Test for parametric and non-parametric data respectively. Differences within-group across time will be compared using Pared t-Test or Wilcoxon Signed Ranks Test for parametric and non-parametric data respectively. A p-value of less than 0.05 will be considered to indicate statistical significance.

Recruitment
Recruitment status
Not yet recruiting
Date of first participant enrolment
Anticipated
2/12/2019
Actual
Date of last participant enrolment
Anticipated
2/03/2020
Actual
Date of last data collection
Anticipated
3/05/2021
Actual
Sample size
Target
50
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
SA
Recruitment postcode(s) [1] 28361 0
5067 - Beulah Park

Funding & Sponsors
Funding source category [1] 304148 0
Charities/Societies/Foundations
Name [1] 304148 0
Channel 7 Children's Research Foundation
Country [1] 304148 0
Australia
Primary sponsor type
University
Name
Flinders University
Address
Sturt Road, Bedford Park 5042, South Australia

Postal address
GPO Box 2100
Adelaide 5001, South Australia
Country
Australia
Secondary sponsor category [1] 304379 0
None
Name [1] 304379 0
Address [1] 304379 0
Country [1] 304379 0
Other collaborator category [1] 281010 0
Individual
Name [1] 281010 0
Dr Billy Tao
Address [1] 281010 0
Department of Paediatrics
Flinders Medical Centre
Flinders Drive
Bedford Park
SA, 5042
Country [1] 281010 0
Australia
Other collaborator category [2] 281011 0
Individual
Name [2] 281011 0
Sarah Cohen-Woods
Address [2] 281011 0
Behavioural Genetics and Environmental Mechanisms Laboratory
Flinders University
Sturt Road
Bedford Park 5042
South Australia
Country [2] 281011 0
Australia
Other collaborator category [3] 281012 0
Individual
Name [3] 281012 0
Luke Grzeskowiak
Address [3] 281012 0
Pharmacy Department
Flinders Medical Centre
Flinders Drive
Bedford Park
SA, 5042
Country [3] 281012 0
Australia
Other collaborator category [4] 281013 0
Individual
Name [4] 281013 0
Tim Chataway
Address [4] 281013 0
Flinders Proteomics Facility
Flinders Medical Centre
Flinders Drive
Bedford Park
SA, 5042
Country [4] 281013 0
Australia
Other collaborator category [5] 281014 0
Individual
Name [5] 281014 0
Scott Morris
Address [5] 281014 0
Department of Neonatal-Perinatal Medicine
Flinders Medical Centre
Flinders Drive
Bedford Park
SA, 5042
Country [5] 281014 0
Australia

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 304630 0
Women’s and Children’s Network Human Research Ethics Committee.
Ethics committee address [1] 304630 0
Research Secretariat, WCHN Human Research Ethics Committee, Level 2, Samuel Way Building, Women’ and Children’s Hospital, 72 King William road, North Adelaide, South Australia, 5006
Ethics committee country [1] 304630 0
Australia
Date submitted for ethics approval [1] 304630 0
05/02/2019
Approval date [1] 304630 0
16/07/2019
Ethics approval number [1] 304630 0
HREC/19/WCHN/38

Summary
Brief summary
Peanut allergy affects up to 3% Australian children and peanut oral immunotherapy (POIT) is the most studied method for peanut desensitization. While results from POIT are generally promising, it is worthy to note that desensitization actually accounts for only the first year of treatment, after which regular maintenance of peanut ingestion demands much longer-term patience and perseverance. This is of great importance because many children dislike the taste of peanut, and it is timely to shift focus from initial safety to ongoing adherence in POIT.

A major design-limitation of all currently published OIT studies is that they do not incorporate a well-structured protocol for maintenance therapy post-desensitization. This may contribute to non-adherence. A well-designed and high-quality post-desensitization RCT is therefore needed to make best use of the time and expense already put into OIT while maintaining the long-term benefit of desensitization in the years that follow.

Successful desensitization can reduce psycho-social morbidity by offering the child protection from accidental ingestion of at least the same amount of desensitization-dose peanut. However, there no studies have been done to compare Quality of Life between adherent and non-adherent subjects post-desensitization. The fact that many desensitized children have opted to drop-out from treatment rather than maintaining ingestion is concerning, and may indicate that the time immediately after desensitization is an inflection point for Quality of Life changes. We think this study will reveal vital data in the understanding of causes and consequences of longer-term poor adherence after initially successful desensitization.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 97646 0
Dr Billy Tao
Address 97646 0
Department of Paediatrics
Flinders Medical Centre
Flinders Drive
Bedford Park
SA, 5042
Country 97646 0
Australia
Phone 97646 0
+61 418802380
Fax 97646 0
61 8 83312788
Email 97646 0
[email protected]
Contact person for public queries
Name 97647 0
Billy Tao
Address 97647 0
Department of Paediatrics
Flinders Medical Centre
Flinders Drive
Bedford Park
SA, 5042
Country 97647 0
Australia
Phone 97647 0
+61 418802380
Fax 97647 0
61 8 83312788
Email 97647 0
[email protected]
Contact person for scientific queries
Name 97648 0
Billy Tao
Address 97648 0
Department of Paediatrics
Flinders Medical Centre
Flinders Drive
Bedford Park
SA, 5042
Country 97648 0
Australia
Phone 97648 0
+61 418802380
Fax 97648 0
61 8 83312788
Email 97648 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
Individual patients could be identifiable from demographic and medical data.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
5500Study protocol    378647-(Uploaded-30-10-2019-12-09-08)-Study-related document.pdf



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