Clinical trial NCT06467994: Boiled Tree Nut for Oral Immunotherapy in Food-allergic Children
Official title: A Randomised, Controlled Trial Evaluating the Effectiveness of Boiled Cashew OraL immunoTherapy (BOLT) in Inducing Desensitisation or Remission in Children With Cashew Nut Allergy Compared With Placebo
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
Conditions: Food Allergy in Children
Food Allergy
Keywords: food allergy
cashew allergy
tree nuts
oral immunotherapy
Lead sponsor: Chinese University of Hong Kong
Sponsor class: OTHER
First posted: 2024-06-21
Enrollment: 75
Sex: ALL
Minimum age (years): 3
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: As the global prevalence of food allergy steadily increases, tree nut (TN) becomes one of the main triggers of food-allergic reactions and food anaphylaxis. Since there is no effective cure, TN-allergic patients and their families must continue to live with this chronic, disabling condition while avoiding allergens and responding to allergic reactions with emergency treatment. An emerging experimental treatment for food allergy is oral immunotherapy (OIT). Tree nut OIT appears promising in preliminary studies but there are concerns about the high risk of adverse reactions to TNs used in the treatment. The rate of remission with TN OIT is also lacking. Identification of OIT regimes with increased efficacy and safety is urgently needed. The investigators revealed that boiled cashews had lower allergenic potential but retained mast cell reactivity. The aim of this proposed study is to investigate the efficacy and safety of a novel treatment strategy for TN-allergic individuals, whereby the investigators hypothesized that consuming increasing quantities of boiled cashews can induce desensitization/ remission to roasted tree nuts in children with cashew allergies.

Detailed description: This will be a two-arm, parallel-design, double-blind, randomized controlled trial. Participants aged 3-17 years of age with double blind placebo-controlled food challenge-confirmed cashew allergy will be randomised into either the active or placebo arm. The active and placebo participants will consume daily dose of cashew and placebo, respectively, for 52 weeks. Participants will undergo an initial escalation and build-up phase until they reach a maintenance dose of cashew or placebo. Participants will return at 6 months for a safety and compliance check and at 12 months (T1) and 14 months (T2) for endpoint oral food challenges. Level of cross-desensitization to pistachio will be examined at T1. Immunological changes, including sIgE and IgG4, will be examined.

Eligibility criteria: Inclusion Criteria:

* Aged between 3 year and 17 years of age;
* Either sex, and of any race and ethnicity;
* \>7kg (the weight considered safe for the administration of an adrenaline autoinjector) (e.g. Jext);
* Confirmed diagnosis of cashew nut allergy as defined by a failed DBPCFC with cashew nut and a positive SPT (\>=3mm than control) or sIgE to cashew nut (of at least 0.35 kUA) at screening.
* Subject's parent and/ or guardian must be able to understand and provide informed consent.

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)
* Any disorder in which adrenaline is contraindicated (such as hypertension or cardiac rhythm disorders)
* Reacting to the placebo component during the study entry DBPCFC
* FEV1 \<85% at rest and FEV1/FVC ≤ 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, ACE inhibitors or calcium channel blockers
* 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
* Have received other food immunotherapy treatment in the preceding 6 months
* Currently taking immunomodulatory therapy (including allergen immunotherapy)
* Therapy with anti-IgE or other biologics within 1 year of enrolment
* 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 NOTE: participants with other food allergies are NOT excluded from participating in this trial.

Primary outcomes:
measure: Proportion of cashew-allergic subjects who by T1 DBPCFC tolerate the full challenge i.e. a cumulative dose of 3180 mg cashew protein
timeFrame: T1 - One day after final day of maintenance treatment
Secondary outcomes:
measure: Proportion of participants with 8-week sustained unresponsiveness (passed T1 and T2 challenges) in OIT vs placebo groups
timeFrame: T2 - 8 weeks after final day of maintenance treatment
measure: The cumulative dose tolerated during the T1 challenge (cumulative doses below the reaction-eliciting dose if there is a reaction; or total cumulative challenge dose if there is no reaction) in OIT vs placebo groups
timeFrame: T1 - One day after final day of maintenance treatment
measure: Exposure-adjusted incidence rate and severity of treatment emergent adverse events (TEAEs) in OIT vs placebo groups;
timeFrame: T1 - One day after final day of maintenance treatment
measure: SPT wheal size to cashew (at the end of treatment, and at 8 weeks after end of treatment) in OIT vs placebo groups.
timeFrame: T1 - One day after final day of maintenance treatment
measure: Cashew-specific IgE levels (at the end of treatment, and at 8 weeks after end of treatment) in OIT vs placebo groups.
timeFrame: T1 - One day after final day of maintenance treatment
measure: Cashew-specific IgG4 levels (at the end of treatment, and at 8 weeks after end of treatment) in OIT vs placebo groups.
timeFrame: T1 - One day after final day of maintenance treatment
Other outcomes:
Locations:
city: Hong Kong
country: Hong Kong
facility: Department of Paediatrics, Prince of Wales Hospital, The Chinese University of Hong Kong
Study officials:
References: