None listed
Conditions
Brief summary
Childhood peanut allergy is increasing, affecting 3% of Australian children. It is the food allergy that persists into adult life, and the most likely to be associated with death due to accidental exposure. It involves the allergy antibody, IgE, which stimulates allergy cells to release chemicals that cause allergic symptoms. There is no current cure. Management is by avoidance with emergency plans and medication in case of accidental exposure. Immunotherapy (IT) is thought to be the most likely strategy to offer a “cure” for food allergy. Immunotherapy has been shown to be effective in the management of aeroallergen and venom allergy. This technique involves regular and prolonged exposure to the allergen in question, initially starting with very small doses and then increasing the dose over a period of time to a level where the person does not respond with an allergic reaction when re-exposed to it. Food immunotherapy trials have so far only had a few participants and often achieved only temporary desensitization which is lost rapidly when treatment is stopped, and also have a high rate of side effects. Gut microbes are implicated in food allergy. They can increase the levels of small chain fatty acids (SCFA), namely acetate, butyrate and propionate, in the gut by fermenting fibre- leading to significant changes to bacteria present in the gut (i.e. the gut microbiome), with increased beneficial bacteria promoting a non-allergic environment. Experiments in mice fed a high-fiber diet or SCFAs found they were protected from food allergy. In particular, they had increased oral tolerance to peanuts with an increase in the number and function of immune cells important in controlling allergic reactions . This study aims to examine whether using a dietary fibre supplement which is high in a key short chain fatty acid- butyrate -whilst using small and increasing daily doses of peanut in peanut allergic children and teenagers will provide them with sustained unresponsiveness to peanut and render them non allergic (or tolerant ) to peanut.
Interventions
Participants will be randomised to receive peanut immunotherapy (study arms A and B) with or without active dietary fibre adjuvant for 12 months. Peanut immunotherapy will use roasted peanut in small and gradually increasing incremental doses starting at 5mg (given in powder form), followed by 10mg (powder), 20mg (powder), 40mg (powder), 80mg (powder), 125mg (one half of a peanut), 250mg (1 peanut), 500mg (2 peanuts), 750mg (3 peanuts), 1000mg (4 peanuts), 1250mg (5 peanuts), 1500mg (6 peanuts),
Participants will be randomised to receive peanut immunotherapy (study arms A and B) with or without active dietary fibre adjuvant for 12 months. Peanut immunotherapy will use roasted peanut in small and gradually increasing incremental doses starting at 5mg (given in powder form), followed by 10mg (powder), 20mg (powder), 40mg (powder), 80mg (powder), 125mg (one half of a peanut), 250mg (1 peanut), 500mg (2 peanuts), 750mg (3 peanuts), 1000mg (4 peanuts), 1250mg (5 peanuts), 1500mg (6 peanuts), 1750mg (7 peanuts) and 2000mg (8 peanuts) (see below table), Updosing of the roasted peanut will occur during a visit supervised by medical members of the research team approximately every 2 weeks until week 28 (depending on the development of adverse events. The participant will be asked to take a slightly smaller dose at home than what they were given during the updosing visit in hospital. A minimum of 2 weeks will be needed at each dose, however a participant may be on a dose for extended periods if they developed symptoms suggestive of an adverse reaction on a higher dose, or if they missed more than 2 days at during any dose period. A dietary supplement - butyrylated high amylase maize starch (HAMSB) will be ingested daily for 12 months by participants in study arm B. The dose is stratified by weight: those 50kg or over at study entry will have 40g of HAMSB daily; those under 50kg at study entry will consume 20g of HAMSB daily. This can be mixed into a range of foods, such as flavoured milk, juice, custards, pasta sauce. To ensure that any symptoms from peanut OIT are not inaccurately attributed to HAMSB, participants will take HAMSB for 2 weeks prior to starting peanut OIT. The doses will be the same as above and participants will document any adverse events in their diary. Adherence to the schedule will be assessed by diary reviews (participants will enter the date, time and dose of peanut taken) as well as return of the empty containers that held the peanut doses. Table: Peanut protein dosing (at visit and taken at home) at visits 4 to 18 and the minimum number of weeks at the dose (cumulative). Visit:4 At visit: 10mg At home: 5mg Minimum number of weeks at this dose: 3 Visit:5 At visit: 15mg At home: 10mg Minimum number of weeks at this dose: 3 (6) Visit:6 At visit: 25mg At home: 20mg Minimum number of weeks at this dose: 2 (8) Visit:7 At visit: 50mg At home: 40mg Minimum number of weeks at this dose: 2 (10) Visit:8 At visit: 100mg At home: 80mg Minimum number of weeks at this dose: 2 (12) Visit:9 At visit: 150mg At home: 125mg Minimum number of weeks at this dose: 2 (14) Visit:10 At visit: 300mg At home: 250mg Minimum number of weeks at this dose: 2 (16) Visit:11 At visit: 600mg At home: 500mg Minimum number of weeks at this dose: 2 (18) Visit:12 At visit: 800mg At home: 750mg Minimum number of weeks at this dose: 2 (20) Visit:13 At visit: 1200mg At home: 1000mg Minimum number of weeks at this dose: 2 (22) Visit:14 At visit: 1500mg At home: 1250mg Minimum number of weeks at this dose: 2 (24) Visit:15 At visit: 1750mg At home: 1500mg Minimum number of weeks at this dose: 2 (26) Visit:16 At visit: 2000mg At home: 1750mg Minimum number of weeks at this dose: 2 (28) Visit:17 At visit: 2500mg At home: 2000mg Minimum number of weeks at this dose: 2 (52) Visit:18 At visit: 0mg At home: 0mg Minimum number of weeks at this dose: 6 (58):
Sponsors
Sydney Children's Hospital Network
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
10 Years to 16 Years
Healthy volunteers
No
Inclusion criteria
Children aged 10-16 years with a diagnosis of peanut allergy with a positive skin prick test to a commercially available peanut extract (wheal at least 3mm larger than the negative control) and confirmation of clinical reactivity to roasted peanut in a double blind, placebo-controlled food challenge (DBPCFC) with a cumulative threshold of >9mg but <3000mg of peanut protein; tolerant of soy (DBPCFC is given in a soy-based matrix) at a food challenge; parents, or legal guardians, must give informed consent and the child must also agree to partake in the study.
Exclusion criteria
Previous admission to intensive care unit for the management of a peanut allergic reaction; clinically significant chronic disease other than eczema, rhinitis or asthma; poorly controlled asthma in the last 3 months (as defined by clinican judgement with reference to the ICON consensus) or asthma requiring oral corticosteroids in the previous 3 months; those in the first year of immunotherapy (subcutaneous or sublingual) for respiratory allergens; those receiving anti-IgE therapy, oral immunosuppressants, beta-blockers or ACE inhibitor therapy; a clinical allergy to soya or sunflower seed; tolerance to roasted peanut in a double blind, placebo-controlled food challenge with thresholds <10mg or 3000mg or more peanut protein; pregnancy; or unwilling or being unable to fulfil study requirements.
Outcome results
None listed