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Trial registered on ANZCTR


Registration number
ACTRN12618000235202
Ethics application status
Approved
Date submitted
1/02/2018
Date registered
14/02/2018
Date last updated
28/10/2021
Date data sharing statement initially provided
28/10/2021
Type of registration
Prospectively registered

Titles & IDs
Public title
Randomised, controlled trial evaluating the effectiveness of Probiotic and prawn oral Immunotherapy at inducing desensitisation or tolerance in participants with Prawn Allergy compared with placebo (Probiotic and prawn Immunotherapy for treatment of Prawn Allergy: PIPA study)
Scientific title
A phase 2b, dual-centre, randomised, placebo controlled trial evaluating the effectiveness of Probiotic and prawn oral Immunotherapy at inducing desensitisation or tolerance in participants with Prawn Allergy compared with placebo (Probiotic and prawn Immunotherapy for treatment of Prawn Allergy: PIPA study)
Secondary ID [1] 293934 0
Nil known
Universal Trial Number (UTN)
Trial acronym
Probiotic and prawn Immunotherapy for treatment of Prawn Allergy: PIPA study
Linked study record

Health condition
Health condition(s) or problem(s) studied:
Prawn allergy 306420 0
Condition category
Condition code
Inflammatory and Immune System 305508 305508 0 0
Allergies

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Participants will be randomised 1:1 into an active (probiotic and prawn immunotherapy) or placebo arm (placebo).
All participants begin the trial on 10 mg of prawn powder or placebo which will increase until final dose of 3000 mg (either prawn powder or placebo). A daily dose of L rhamnosus strain probiotic (or placebo) is also taken. This is mixed in water or milk and is to be given immediately prior to the prawn / placebo dosing.
If a participant does not tolerate a dose, they will go home on the dose before they reacted. This will mean that they will have an extended build up period as extra doses will be added to the schedule (ie the remaining doses from day 1)
The participants are to continue having the doses daily at home at a time suitable for them / their family. Every fortnight they will visit the hospital to increase their dose under supervision. They will be given as a mixture of capsules and sachets (depending on the dose). The participant will be required to open the capsule or sachet and mix the powder with a suitable mixing medium (soup, rice or a food the participant enjoys). The whole dose is to be eaten immediately.
If a participant does not tolerate a dose, they will remain on the last dose tolerated for a further 7-14 days and attempt the build up again.
They remain on the maintenance dose for the remainder of the active phase of the trial. The active phase of the trial goes for 18 months.
The participants will be required to fill in a diary every day to monitor compliance and reactions. Pharmacy also count the returned capsules / sachets to ensure compliance.
Intervention code [1] 300199 0
Treatment: Other
Intervention code [2] 300227 0
Treatment: Drugs
Comparator / control treatment
the placebo prawn product is currently in its development stage.
The placebo probiotic will be maltodextrin powder
Control group
Placebo

Outcomes
Primary outcome [1] 304641 0
The proportion of subjects who attain sustained unresponsiveness (at 8 weeks after end-of-treatment) in active and placebo groups. Participants who pass the end of treatment challenge will be re-challenged after 8 weeks of no treatment. Those who pass the food challenge will be considered to have achieved sustained unresponsiveness, those that don't pass will not.
Timepoint [1] 304641 0
20 months post commencement of treatment
Secondary outcome [1] 342651 0
The proportion of subjects who attain desensitisation (at end-of treatment) in active and placebo groups. The participants will be challenged at the end of study treatment. Those that pass will be considered desensitised, those that do not, wont.
Timepoint [1] 342651 0
18 months post commencement of treatment

(the treatment goes for 18months. there is a challenge at 18 months. if they pass this challenge they are desensitised.) primary outcome is 8 weeks after this challenge, at 20 months.
Secondary outcome [2] 342652 0
The proportion of subjects who are eating prawn in their diet 12 months after end-of-treatment in active and placebo groups. This will be captured using a follow up diary which will be given at either end of treatment (if they fail the first challenge) or at 8 weeks post end of treatment.
Timepoint [2] 342652 0
32 months post commencement of treatment
Secondary outcome [3] 342653 0
Prawn skin prick test (SPT) wheal size at study entry, end-of-treatment, and 8 weeks and 12 months after end-of-treatment in active and placebo groups.
Timepoint [3] 342653 0
Study entry, 18 months post commencement of treatment, 20 months post commencement of treatment and 32 months post commencement of treatment.
Secondary outcome [4] 342654 0
To assess changes in sIgE and sIgG4 levels to prawn and prawn components (Pen m1,2,3,4) at study entry, end-of-treatment, and 8 weeks and 12 months after end-of-treatment in active and placebo groups. The serum/plasma will be stored at -80C for batched analysis. Serum/plasma levels of sIgE and sIgG4 against prawn will be measured by ImmunCAP (Phadia AB, Uppsala, Sweden) at MCRI, and against and prawn components (Pen m1,2,3,4) by a ELISAs at James Cook University.
Timepoint [4] 342654 0
Study entry, 18 months post commencement of treatment , 20 months post commencement of treatment and 32 months post commencement of treatment
Secondary outcome [5] 342656 0
To compare quality of life at pre-treatment and 12 months AFTER end-of-treatment in active and placebo groups. This will be captured by administering the FAQLQ-PF
Timepoint [5] 342656 0
32 months post commencement of treatment

Eligibility
Key inclusion criteria
Confirmed diagnosis of Tiger prawn allergy as defined by a failed DBPCFC with Tiger prawn and a positive SPT or sIgE to prawn or a P monodon allergen component at screening
Minimum age
5 Years
Maximum age
30 Years
Sex
Both males and females
Can healthy volunteers participate?
No
Key exclusion criteria
• History of severe anaphylaxis (as defined by persistent hypotension, collapse, loss of consciousness, persistent hypoxia or ever needing more than three (3) doses of intramuscular adrenaline or an intravenous adrenaline infusion for management of an allergic reaction)
• Severe anaphylaxis during the study entry DBPCFC (defined as persistent hypotension, collapse, loss of consciousness, persistent hypoxia, or requiring more than 3 doses of intramuscular adrenaline or an intravenous adrenaline infusion for management of an allergic reaction)
• FEV1 less than 85% at rest and FEV1/FVC less than or equal to 85% at rest or ongoing chronic persistent asthma (as per Australian Asthma Foundation guidelines)
• Underlying medical conditions (e.g. cardiac disease) that increase the risks associated with anaphylaxis
• Use of beta-blockers, and ACE inhibitors
• Inflammatory intestinal conditions, indwelling catheters, gastrostomies, immune-compromised states, post-cardiac and/or gastrointestinal tract surgery, critically-ill and those requiring prolonged hospitalisation or other conditions that may increase the risks of probiotic associated sepsis
• Already taking probiotic supplements within the past 6 months
• Reacting to the placebo component during the study entry DBPCFC
• Have received other food immunotherapy treatment in the preceding 12 months
• Currently taking immunomodulatory therapy (including allergen immunotherapy)
• Past or current major illness that in the opinion of the Site Investigator may affect the subject’s ability to participate in the study e.g. increased risk to the participant
• Subjects who in the opinion of the Site Investigator are unable to follow the protocol
• Another family member already enrolled in the trial (to maintain safety and blinding)

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)
Central randomisation
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Simple randomisation using a randomisation table created by computer software
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
Phase 2
Type of endpoint/s
Efficacy
Statistical methods / analysis
The study sample size will be 80 participants, randomly allocated in a 1:1 ratio to active (n=40), and placebo (n=40). An effective treatment for food allergy should induce sustained unresponsiveness in at least 50% of subjects to be worthwhile.
Allowing for a 12% drop-out rate, 40 participants in each group provides 90% power to detect the difference between a 20% rate of sustained unresponsiveness in the placebo group and a 60% rate in the active group, using a 2 group continuity corrected chi2 test with 0.05 two sided significance.

Recruitment
Recruitment status
Withdrawn
Reason for early stopping/withdrawal
Other reasons/comments
Other reasons
Changed to egg as prawn powder was too difficult to source
Date of first participant enrolment
Anticipated
1/10/2018
Actual
Date of last participant enrolment
Anticipated
1/04/2020
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
80
Accrual to date
Final
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment hospital [1] 9924 0
The Royal Childrens Hospital - Parkville
Recruitment postcode(s) [1] 18736 0
3052 - Parkville
Recruitment outside Australia
Country [1] 9542 0
Singapore
State/province [1] 9542 0
Singapore

Funding & Sponsors
Funding source category [1] 298562 0
Government body
Name [1] 298562 0
NHMRC grant
Country [1] 298562 0
Australia
Primary sponsor type
Individual
Name
Mimi Tang
Address
Murdoch Children's Research Institute
50 Flemington Road
Parkville, 3052, Vic
Country
Australia
Secondary sponsor category [1] 297713 0
None
Name [1] 297713 0
Address [1] 297713 0
Country [1] 297713 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 299529 0
Royal Children's Hospital Ethics committee
Ethics committee address [1] 299529 0
Ethics committee country [1] 299529 0
Australia
Date submitted for ethics approval [1] 299529 0
07/02/2018
Approval date [1] 299529 0
18/07/2018
Ethics approval number [1] 299529 0

Summary
Brief summary
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 80738 0
Prof Mimi Tang
Address 80738 0
Murdoch Children's Research Institute
50 Flemington Road
Parkville, 3052, Victoria
Country 80738 0
Australia
Phone 80738 0
+61393455911
Fax 80738 0
Email 80738 0
[email protected]
Contact person for public queries
Name 80739 0
Sigrid Pitkin
Address 80739 0
Murdoch Children's Research Institute
50 Flemington Road,
Parkville, 3052, Victoria
Country 80739 0
Australia
Phone 80739 0
+61393456068
Fax 80739 0
Email 80739 0
[email protected]
Contact person for scientific queries
Name 80740 0
Mimi Tang
Address 80740 0
Murdoch Children's Research Institute
50 Flemington Road,
Parkville, 3052, Victoria
Country 80740 0
Australia
Phone 80740 0
+61393455911
Fax 80740 0
Email 80740 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
The study protocol, documentation, data and all other information generated will be held in strict confidence. No information concerning the study or the data will be released to any unauthorised third party, without prior written approval of the sponsoring institution.
Authorised representatives of the sponsoring institution may inspect all documents and records required to be maintained by the Site Investigator, including but not limited to, medical records (office, clinic or hospital) and pharmacy records for the participants in this study.
All laboratory specimens, evaluation forms, reports and other records that leave the site will be identified only by the Participant Identification Number (SID) to maintain participant confidentiality. Clinical information will not be released without written permission of the participant, except as necessary for monitoring by HREC or regulatory agencies.


What supporting documents are/will be available?

No Supporting Document Provided



Results publications and other study-related documents

Documents added manually
No documents have been uploaded by study researchers.

Documents added automatically
No additional documents have been identified.