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Analysing HIgh Dose Probiotic Peanut Oral Immunotherapy (PPOIT) and High Dose Peanut Oral Immunotherapy (OIT) Versus LOw Dose Peanut OIT for Peanut Allergy

Phase 2
Withdrawn
Conditions
Peanut Allergy
Interventions
Dietary Supplement: Probiotic (LGG®, Lactobacillus Rhamnosus) or placebo probiotic (maltodextrin)
Registration Number
NCT06297083
Lead Sponsor
Murdoch Childrens Research Institute
Brief Summary

This study will compare the effectiveness of three different treatments to treat peanut allergy

Detailed Description

This is a three-arm, multi-centre, head-to-head randomised trial, comparing two treatments against a low dose oral immunotherapy approach for peanut allergy.

One hundred and thirty children aged 1 year to 10 years with current peanut allergy confirmed by failed double-blind placebo-controlled food challenge (DBPCFC) at study screening will be recruited for this study. Participants will be recruited from The Royal Children's Hospital Melbourne, Women's and Children's Hospital (Adelaide) and from the general community.

Participants will be randomized to:

1. High-dose rapid escalation peanut OIT combined with probiotic (HD PPOIT)

2. High-dose rapid escalation peanut OIT combined with probiotic placebo (HD OIT)

3. Low-dose slow escalation peanut OIT combined with probiotic placebo (LD OIT)

The length of the treatment period for each participant is 18 months and the post-treatment follow up period is 12 months

Recruitment & Eligibility

Status
WITHDRAWN
Sex
All
Target Recruitment
Not specified
Inclusion Criteria
  • Aged 1-10 years.
  • >7kg (the weight considered safe for the administration of an adrenaline injector);
  • Confirmed diagnosis of peanut allergy as defined by a failed DBPCFC with peanut and a positive SPT or sIgE to peanut at screening;
  • Has a legally acceptable representative capable of understanding the informed consent document and providing consent on the participant's behalf
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)
  • 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 angiotensin converting enzyme (ACE) inhibitors
  • 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
  • History of suspected or biopsy-confirmed eosinophilic oesophagitis (EoE)
  • 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 blinding, safety and equity of access) or in any other clinical trial from the same study group.

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
Low-dose peanut OIT combined with probiotic placebo (LD OIT)Peanut Oral Powder [PEANUT POWDER]Low-dose slow escalation peanut OIT combined with probiotic placebo (LD OIT) taken daily for 18 months.
High-dose peanut OIT combined with probiotic (HD PPOIT)Peanut Oral Powder [PEANUT POWDER]High-dose rapid escalation peanut OIT combined with probiotic (HD PPOIT) taken daily for 18 months.
High-dose peanut OIT combined with probiotic (HD PPOIT)Probiotic (LGG®, Lactobacillus Rhamnosus) or placebo probiotic (maltodextrin)High-dose rapid escalation peanut OIT combined with probiotic (HD PPOIT) taken daily for 18 months.
High-dose peanut OIT combined with probiotic placebo (HD OIT)Peanut Oral Powder [PEANUT POWDER]High-dose rapid escalation peanut OIT combined with probiotic placebo (HD OIT) taken daily for 18 months
High-dose peanut OIT combined with probiotic placebo (HD OIT)Probiotic (LGG®, Lactobacillus Rhamnosus) or placebo probiotic (maltodextrin)High-dose rapid escalation peanut OIT combined with probiotic placebo (HD OIT) taken daily for 18 months
Low-dose peanut OIT combined with probiotic placebo (LD OIT)Probiotic (LGG®, Lactobacillus Rhamnosus) or placebo probiotic (maltodextrin)Low-dose slow escalation peanut OIT combined with probiotic placebo (LD OIT) taken daily for 18 months.
Primary Outcome Measures
NameTimeMethod
Difference between the treatment arms in the proportion of participants who achieve remission of peanut allergy at 8 weeks post treatment.22 months

Remission will be assessed 8 weeks after the end of treatment timepoint and is defined as passing (completing without reaction) the double-blind placebo controlled food challenge (DBPCFC) at the end of treatment and at 8 weeks post treatment

Secondary Outcome Measures
NameTimeMethod
Difference between the treatment arms in the exposure-adjusted event rate of adverse events (AE)20 months

The total number of treatment-related AE the participant reports during the course of treatment adjusted for the time the participant is on treatment (in years)

Difference between treatment arms in changes in the peanut skin prick test (SPT) wheal size.Baseline, 76 weeks, 84 weeks,128 weeks

Skin prick test to whole peanut extract

Difference between treatment arms in change from baseline peanut specific immunoglobulin E (sIgE) levelsBaseline, 76 weeks, 84 weeks,128 weeks

Blood samples will be collected and levels of sIgE against peanut will be measured by ImmunoCAP (Phadia AB, Uppsala, Sweden)

Difference between the treatment arms in the proportion of participants who achieve full desensitisation of peanut allergy at end of treatment20 months

Full desensitisation will be defined by participants passing (completing without reaction) the double-blind placebo controlled food challenge (DBPCFC) undertaken at the end of treatment

Difference between treatment arms in changes in Quality of Life Scores using the Food Allergy Quality of Life Questionnaires (FAQLQ).Baseline, 22weeks, 76 weeks, 84 weeks, 128 weeks

FAQLQ total score, as well as three sub-scores (food anxiety, general emotional impact, and social and dietary limitations) will be calculated as per the instrument scoring manual

Difference between treatment arms in adherence to treatment regime as measured by daily treatment doses taken by the participant20 months

Adherence to treatment will be monitored by reviewing the participant diary

Difference between treatment arms in participant experience as assessed from qualitative interviews20 months

Interview guide developed and conducted, recorded, transcribed verbatim, and responses explored using framework analysis

Difference between clinical outcome groups in cost using the Consolidated Health Economic Evaluation Reporting Standards (CHEERS)Baseline through to 32 months

Captured per number of hospitalizations, Emergency room (ER) visits, General Practitioner (GP) visits and medications / number of prescriptions required. Data acquired using participant questionnaires, participant study diaries and supplemented by administrative hospital data linkage

Difference between clinical outcome groups in quality adjusted life year (QALY) will be estimated at 32 months using the Food Allergy Quality of Life Form (FAQLQ) mapped to the generic health utility instrument Assessment of Quality of Life-6D (AQoL-6D)32 months
Difference between clinical outcome groups in peanut ingestion from end of treatment to 12 months post treatment20 months to 32 months

Peanut ingestion data will be captured from the participant's study diary

Difference between clinical outcome groups in reactions to peanut from end of treatment to 12 months post treatment20 months to 32 months

Number of reactions, symptoms experienced, and treatment administered will be captured from the participant's study diary

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