None listed
Conditions
Brief summary
This study is a feasibility study designed to establish the safety and tolerability of a food based multi-nut oral immunotherapy (OIT) protocol in children under 6 years of age in WA, We hypothesize that multi-nut OIT will be a practical approach to desensitising children with multiple nut allergies in this age group. Participants with peanut and/or tree nut allergy will receive multi-nut OIT (almond, cashew, hazelnut, walnut and peanut) for 12 months. Children will otherwise avoid those nuts in their diet to which they are confirmed to be allergic at study entry, while those nuts that were tolerated at study entry can be eaten as desired in addition to the OIT doses. Treatment adherence and adverse reactions will be monitored via a daily electronic diary in addition to regular assessment by study clinicians at each visit and monthly telephone calls. Quality of life data will be collected prior to, during and at end of treatment. After 12 months, all participants will undergo an oral food challenge (OFC) to establish whether they are desensitised to the nuts to which they were allergic to at the start of the study.
Interventions
The intervention is a multi-nut oral immunotherapy (OIT) (almond, cashew, hazelnut, walnut and peanut) daily for 12 months.
The intervention will consist of incrementally increasing doses of a mixture of five nut flours (almond, cashew, hazelnut, walnut and peanut) that are combined in a fixed ratio to achieve an equal protein content of each nut in a single product administered over a period of 12 months. All participants will receive the same multi-nut flour regardless of which nuts they hav
The intervention is a multi-nut oral immunotherapy (OIT) (almond, cashew, hazelnut, walnut and peanut) daily for 12 months. The intervention will consist of incrementally increasing doses of a mixture of five nut flours (almond, cashew, hazelnut, walnut and peanut) that are combined in a fixed ratio to achieve an equal protein content of each nut in a single product administered over a period of 12 months. All participants will receive the same multi-nut flour regardless of which nuts they have a confirmed allergy to. The individual nut flours are food products, organic defatted nut flour, manufactured by Healthy Food Crew (ABN 85 168 410 482) and supplied by Mini Mixers Pty. Ltd., Ripponlea Victoria (ABN 29 445 850 847). These nut flours will also be used for the OFCs. The multi-nut OIT investigational product will provided to participants in pre-packaged individual daily doses, to ensure accurate daily administration of each nut. The investigational product will be compounded by the Australian Approved Manufacturer, Optima Ovest, Western Australia, in accordance with the Australian Code of Good Manufacturing Practice (TGA licence MI-2012-LI-00060-3). Optima Ovest will prepare all OIT doses (increments from 0.5mg to 250mg of each nut protein), master labelled and provided in batches to Clinical Trials Pharmacy at PCH for participant dispensing. OIT doses will be mixed into the participant’s usual food of choice that has been previously tolerated throughout all stages of the study. Parents will receive training on the administration of doses during dose escalation and up-dosing visits at PCH. Other than the daily OIT treatment participants will otherwise follow strict avoidance of the nuts to which they have a confirmed allergy. Participants may continue to eat the nuts they tolerate as part of their normal diet. Multi-nut dosing schedule 1) Treatment initiation Subjects receive up to 5 increasing doses of multi-nut flour every 20 minutes to reach a final dose of 15mg of each nut protein (0.5mg, 1mg, 3mg, 10mg, 15mg). If a subject reacts during TI, the next day they will commence dosing at home with the dose immediately below the one that provoked onset of symptoms. 2) Updosing Updosing will occur approximately every 2 weeks for a minimum of six visits, until a maximum dose of 250mg of each nut protein (total combined dose of 1.25g nut protein) is reached (30mg, 60mg, 90mg, 120mg, 180mg, 250mg). The first dose of each new increment is administered under clinical supervision at PCH during a scheduled up-dosing appointment. Participants will remain under observation for at least 2 hours after an up-dose, or until deemed suitable for discharge. 3) Maintenance Participants will continue to take daily doses of maintenance multi-nut flour until a total of 12 months of treatment is completed. The maintenance dose is 250mg of each nut protein (total combined dose of 1.25g nut protein). Compliance and Adverse Events Parents will use an electronic daily diary based in the REDCap platform to record information about their daily dosing and any adverse events they experience. Side effects are common with OIT, and it is anticipated that some children will experience mild (pruritus, swelling or rash, abdominal discomfort or other transient symptoms), moderate ( persistent hives, increased abdominal discomfort/ increased vomiting) and severe (anaphylaxis) allergic reactions to their peanut OIT. All adverse events will be recorded in the electronic diary and monitored by study staff. If allergic symptoms develop following a dose of OIT at home, the parent or guardian will treat the symptoms in line with their prescribed Allergy Action Plan, using rescue medication as required. For any ongoing symptoms, or sudden onset of severe symptoms the families will be requested to alert study staff. The site investigators will decide based on the nature of the symptoms, the plan for continuation of dosing (including plans for reintroduction of dosing and/or extending the period of time before the next up-dose). If ongoing symptoms are noted, the use of antihistamine or another medication for prophylaxis may be initiated by the study team. If anaphylaxis symptoms develop during home dosing (e.g. wheeze, stridor, difficulty breathing, transient hypotension), the family will be counselled and debriefed on the management of the anaphylaxis. The next dose will be given at home at the previously tolerated dose or under supervision at the same dose via an unscheduled visit, at the discretion of the investigator.
Sponsors
Child and Adolescent Health Service
Study design
Allocation
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
1 Years to 5 Years
Healthy volunteers
No
Inclusion criteria
1) Male or female children from 1-4 years of age (i.e. first visit to occur on or after the participant’s first birthday, and prior to their fifth birthday). 2) Confirmed or highly probably allergy, to at least one of almond, cashew, hazelnut or walnut. Children with other nut allergies (including peanut allergy) are eligible for inclusion, however they must also have a confirmed or highly probable allergy to at least one of almond, cashew, hazelnut or walnut. 3) Parents/guardians and subjects willing to comply with all the study requirements during their participation in the study. Tree nut allergy inclusion definitions (almond, cashew, hazelnut or walnut) a) Confirmed (entry OFC required): Positive SPT (mean wheal diameter >3mm) or specific IgE (>0.35 kU/L) at SV1 and allergic reaction to the tree nut during the entry OFC which meets the stopping criteria. b) Highly probable (entry OFC not required): i) Clinical history of anaphylaxis to the tree nut in the 12 months prior to SV1, with a positive SPT or sIgE at SV1, or ii) Clinical history of a mild to moderate allergic reaction, with signs/symptoms meeting protocol-specified stopping criteria for OFC, to the tree nut in the 4 months prior to SV1 with a positive SPT or sIgE at SV1, or iii) Allergic reaction during an oral food challenge to the nut in the 12 months prior to SV1 (performed as part of usual clinical care), with a positive SPT or sIgE, or iv) For walnut only, any one of the below (1) a skin prick test with mean wheal diameter >8mm in a participant who has no clinical history of reaction to walnut and is avoiding it in their diet, or (2) a SPT with mean wheal diameter >6mm in a participant AND a previous clinical history of an allergic reaction to walnut prior to SV1 v) For cashew only, any two of the following three criteria: (1) A previous clinical history of an allergic reaction to cashew prior to screening (2) Cashew SPT >7mm mean wheal diameter (3) Cashew component Ana o 3 specific IgE >1 kU/L Whilst participants may have a peanut allergy alongside one or more tree nut allergies, it will not affect eligibility for the study
Exclusion criteria
Participants will be excluded if they meet any of the following criteria: 1. History of severe anaphylaxis to any nut prior to study entry, defined as a reaction causing loss of consciousness, persistent hypoxia, or requiring more than three doses of IM adrenaline, an IV adrenaline infusion or intubation for management of an allergic reaction. 2. Use of beta-blockers 3. Participants receiving immunotherapy for food allergy, or who have received immunotherapy for food allergy in the preceding 3 months. 4. Participants currently receiving other oral or sublingual allergen immunotherapy 5. Persistent, uncontrolled asthma. In participants with asthma, symptom control will be assessed at screening using the expert opinion-based schema in the Global Initiative for Asthma (GINA) Global Strategy for Asthma Management and Prevention, whereby uncontrolled asthma is defined as any 3 or more of the following occurring in the preceding 4 weeks a) Daytime asthma symptoms for more than a few minutes, more than once a week b) Any activity limitation due to asthma c) Reliever medication needed more than once a week (excluding reliever taken before exercise) d) Any night waking or night coughing due to asthma Participants may be re-screened after asthma treatment is optimised. 6. Confirmed diagnosis of eosinophilic oesophagitis, and/or uncontrolled symptoms of dysphagia, postprandial abdominal pain or vomiting. 7. Children with other significant underlying medical conditions that place them at increased risk of adverse outcomes in the event of an allergic reaction, such as cardiovascular or respiratory diseases. The Principal Investigator or delegated study doctor will review these children and consult with the child’s usual treating specialist, and the Principal Investigator will confirm that the child is not at increased risk of harm from the study procedures by virtue of their underlying medical condition before enrolling the child in the study. 8. Subjects who in the opinion of the investigator will be unable to follow the protocol
Outcome results
None listed