None listed
Conditions
Brief summary
At present there is no cure for food allergy. People with a food allergy need to avoid the food they are allergic to in order to stay safe. However we know that accidental exposure is common. Research shows that 50% of children with a peanut allergy are accidentally exposed to peanut within 2 years. Researchers have begun to look at the effectiveness of 'oral immunotherapy' as a treatment for food allergy. In oral immunotherapy, patients with food allergy are given small amounts of the food they are allergic to and tested for food allergy after a set amount of time. Results have been mixed. Studies suggest that oral immunotherapy can induce desensitization (short term ability to tolerate the food allergen while the patient continues on therapy) but has a limited ability to induce sustained unresponsiveness (longer term ability to tolerate the food allergen after treatment is stopped for at least 2-4 weeks or longer). We previously conducted a Randomized Controlled Trial to evaluate a novel combination treatment approach involving administration of probiotic together with oral immunotherapy - Probiotic and Peanut Oral Immunotherapy (PPOIT). In our study we found that just over 80% of children who received PPOIT tolerated peanut after stopping treatment for more than 2 weeks compared with only 4% in the placebo group. PPOIT was highly effective at inducing sustained unresponsiveness - if 9 children were treated with PPOIT, 7 would benefit. PPOIT participants received a daily dose of probiotic together with peanut protein (peanut flour) for 18 months. The probiotic was taken as a fixed daily dose. The dose of peanut protein was commenced at very low levels then increased every 2 weeks over a period of 8 months to reach a maintenance dose of 2g peanut protein. This study (PPOIT-III) will build on our previous PPOIT and PPOIT-II study. PPOIT-III is a multi- site randomized controlled trial to evaluate the effectiveness of Probiotic and Peanut Oral Immunotherapy (PPOIT) in inducing desensitisation or tolerance in children with peanut allergy compared with Oral Immunotherapy (OIT) alone and with Placebo. Children will take increasing doses of peanut protein and a set amount of probiotic until a total of 18 months treatment is completed. Children will be tested for peanut allergy at the start of the study, at the end of PPOIT treatment T1 (18 months) and T2 (8 weeks) and T3 (1year) after treatment. The discovery of a safe and tolerable treatment for food allergy will have great public health benefit.
Interventions
Peanut Flour (50% peanut protein) that is prepared under food manufacturing regulations.
PROBIOTIC
The probiotic to be used is Lactobacillus rhamnosus ATCC 53103 (Health World Ltd).
Probiotic will be prepared under strict Food Manufacturing Regulations. Supply will be as dry powder pre-packaged in 350g bottles containing 160g of probiotic. The daily dose of 2x10^10 cfu will be measured using a standardised scoop. Participants will be instructed to mix one scoop of the probiotic in water at a te
Peanut Flour (50% peanut protein) that is prepared under food manufacturing regulations. PROBIOTIC The probiotic to be used is Lactobacillus rhamnosus ATCC 53103 (Health World Ltd). Probiotic will be prepared under strict Food Manufacturing Regulations. Supply will be as dry powder pre-packaged in 350g bottles containing 160g of probiotic. The daily dose of 2x10^10 cfu will be measured using a standardised scoop. Participants will be instructed to mix one scoop of the probiotic in water at a temperature NOT exceeding 38 degrees Celsius. The probiotic must be stored at 4 degrees Celsius. 1. PPOIT- Probiotic and peanut OIT taken daily for 18 months. 2. OIT - Probiotic placebo and peanut OIT taken daily for 18 months. 3. Placebo - Probiotic placebo and OIT placebo taken daily for 18 months. The study consists of: Screening visit occurs within three months prior to Rush Induction Day. T0 Rush Induction is Day 1 of treatment. - On Rush day, participants receive eight increasing doses of peanut (or placebo) oral immunotherapy (OIT) beginning at 0.1mg every 20 minutes. - Nutritional services or an individual independent of the study will prepare the Rush doses. - Peanut protein (or placebo) will be mixed with food (e.g. yoghurt). - A single dose of probiotic (or placebo) (one level scoop mixed into water, at a temperature NOT exceeding 38 degrees Celsius) is to be given immediately prior to the peanut/placebo dosing. - Participants will be monitored (including vital signs and general nursing assessment of the skin and chest) for 2 hours after the last dose during Rush Induction. - The study doctor and study nurse will be present at all times during the Rush Induction. - The Rush Induction will be performed in hospital. - Spirometry will be performed on all participants aged 8 or older, and younger participants who are capable of doing spirometry reproducibly, before the participant receives their first dose of peanut (or placebo) OIT. - Participants who complete the Rush protocol without reaction will commence the Buildup Phase at Dose 9 on the day after the Rush Induction day. - If a participant reacts to one of the doses during Rush Induction, the Rush schedule will be ceased and the participant will commence the Buildup Phase at the dose immediately below the reaction-eliciting dose starting on the day after the Rush Induction day. - The remaining Rush doses that were not completed on day 1 will be incorporated into the Buildup phase (modified Buildup schedule for that subject) and subsequent incremental dose increases will proceed through all remaining doses of the Rush schedule followed by the doses in the Buildup schedule. For example, if a reaction occurs following dose 6, the subject will commence the Buildup phase at the dose 5 amount and will be instructed to start this reduced dose on the following day). BUILDUP Phase - During Buildup, the daily dose of peanut OIT (or placebo OIT) is increased every 2 weeks until a maintenance dose of 2000mg is reached. - Each dose increase will be administered in hospital under medical supervision. - Hospital visits for dose increases (Updose visits) will be scheduled every 2 weeks (except in unavoidable circumstances when a window of +/- 7 days is allowed). Where indicated, dose adjustments will result in deferment of a dose increase to the next scheduled visit. - Spirometry will not be performed as a routine, but may be performed if indicated. - Peanut protein will be mixed into food (e.g. yoghurt not containing Lactobacillus rhamnosus ATCC 53103). - A single dose of probiotic (or placebo) (one level scoop mixed into water, at a temperature NOT exceeding 38°C) is given once daily prior to OIT treatment. - Subjects will be monitored for 2 hours after the treatment has been administered. MAINTENANCE Phase During Maintenance, participants will take a daily dose of 2g of peanut protein (or placebo) and a daily dose of probiotic (or placebo) at home and continue until a total of 18 months treatment is completed. If the subject has not completed a minimum of 6 months on maintenance dosing at 18 months, the total duration of treatment will be extended to ensure a minimum of 6 months maintenance dosing. In unavoidable circumstances (e.g. school camps) the window for Maintenance visits can be +/- 7 days to accommodate parent/participant availability T1 - One Day after final day of maintenance treatment T2 - 8 weeks after final day of maintenance treatment T3 - One year after final day of treatment All groups will be followed up for 1 year after the treatment period. During this time, at 6 months, a telephone interview will be conducted with the participant's parent or guardian to collect information on exposure to peanut/amount of peanut being eaten and allergic reactions. STRATEGIES TO MONITOR ADHERENCE We will monitor adherence by daily dosing diary and weighing / counting contents of returned treatment packages.
Sponsors
Murdoch Childrens Research Institute
Study design
Allocation
Randomised controlled trial
Intervention model
Parallel
Primary purpose
Treatment
Masking
Blinded (masking used) (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
All
Age
1 Years to 10 Years
Healthy volunteers
No
Inclusion criteria
Children are eligible for the study if they meet all of these criteria: - Children aged between 1 year and 10 years of age - greater than 7kg (the weight considered safe for the administration of an Epipen/EpiPen Jr) - Confirmed diagnosis of peanut allergy as defined by a failed Double-Blind, Placebo-Controlled Food Challenge (CBPCFC) with peanut and a positive SPT or SIgE to peanut at screening.
Exclusion criteria
Children are not eligible for the study if they meet any of these criteria: - History of severe anaphylaxis (as defined by persistent hypotension, collapse, loss of consciousness, persistent hypoxia or ever needing more than three 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 three or more doses of intramuscular adrenaline or an intravenous adrenaline infusion for management of an allergic reaction) - FEV1 less than 85% at rest and FEV1/FVC is 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 (does not include formula) - 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)
Outcome results
None listed