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 conducted a RCT 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-II) will build on our previous PPOIT study.
Interventions
PEANUT FLOUR
Peanut Flour (50% peanut protein) is purchased from a US company (Golden Peanut Company, LTD.
PROBIOTIC (Lactobacillus rhamnosus GG; ATCC 53103)
The probiotic to be used is Lactobacillus rhamnosus GG.
Probiotic will be prepared under strict Food Manufacturing Regulations. Supply will be as dry powder. The daily dose of 2x10^10 cfu will be measured using a 4g scoop. Participants will be instructed to mix the probiotic in water, soy milk or cow’s milk, at a temperature NOT exceeding
PEANUT FLOUR Peanut Flour (50% peanut protein) is purchased from a US company (Golden Peanut Company, LTD. PROBIOTIC (Lactobacillus rhamnosus GG; ATCC 53103) The probiotic to be used is Lactobacillus rhamnosus GG. Probiotic will be prepared under strict Food Manufacturing Regulations. Supply will be as dry powder. The daily dose of 2x10^10 cfu will be measured using a 4g scoop. Participants will be instructed to mix the probiotic in water, soy milk or cow’s milk, at a temperature NOT exceeding 38 degrees Celsius. TREATMENTS AND DOSAGE DAY 1 RUSH INDUCTION * In the rush phase, subjects will receive increasing doses of peanut oral immunotherapy every 20 minutes to reach a final dose of 12mg of peanut protein (cumulative dose 24mg peanut protein). * There will be a maximum of 8 doses administered at a starting dose of 0.1mg. * Peanut protein will be sprinkled onto food (yoghurt not containing LGG). * Subjects will receive a single dose of 2x10^10 cfu LGG ( one level scoop mixed into 100 ml of water, at a temperature NOT exceeding 38 degrees Celsius) prior to initiation of the rush phase. * Probiotic will be administered just prior to the first dose of peanut protein on the rush day and once daily just prior to peanut protein doses throughout the build up and maintenance phases. * Subjects will be monitored (including at least half hourly vital signs and general nursing assessment of the skin and chest) for 2 hours after the last dose during modified rush. * The study doctor and study nurse will be present at all times during the rush phase * The rush phase 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 oral immunotherapy and 2 hours after receiving the final dose of Day 1 rush induction. * Subjects who complete the rush protocol without reaction will commence the Buildup Phase at a daily dose of 25mg peanut protein (Dose 9) on the day after the rush induction day. * If a subject reacts to one of the doses during rush induction, the rush schedule will be ceased and they 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). BUILD UP PHASE In the buildup phase, the daily dose of peanut OIT will be 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. Where indicated, dose adjustments will result in deferment of a dose increase to the next scheduled visit. * 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 increased dose of peanut oral immunotherapy and 2 hours after receiving the dose. * Peanut protein will be sprinkled onto food (e.g. yoghurt not containing LGG). * Subjects will also take a fixed dose of 2x10^10 cfu LGG (one level scoop mixed into 100 ml of water, at a temperature NOT exceeding 38 degrees Celsius) once daily prior to the OIT treatment. * Subjects will be monitored for 2 hours after the treatment has been administered. MAINTENANCE PHASE A maintenance phase, during which participants take a daily dose of 2g peanut protein and a daily dose of 2x10^10 cfu LGG at home, is continued until a total of 18 months PPOIT 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. 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
Non-randomised trial
Intervention model
Single group
Primary purpose
Treatment
Masking
Open (masking not used)
Eligibility
Sex/Gender
All
Age
1 Years to 12 Years
Healthy volunteers
No
Inclusion criteria
Children are eligible for the study if they: * Are aged between 1 year and 12 years of age, * If they are >10kg (weight considered safe for the prescription and administration of an Epipen) * There is a confirmed diagnosis of peanut allergy as defined by a failed DBPCFC to peanut and a positive SPT or sIgE to peanut at screening.
Exclusion criteria
Children will not be eligible for the study if they have a history of: * Severe anaphylaxis (as defined by hypotension , collapse, loss of consciousness or hypoxia OR ever needing three (3) or more doses of intramuscular adrenaline or needing intravenous adrenaline infusion for management of anaphylactic reaction) * FEV1 <85% at rest or FEV1/FVC < 85% at rest or ongoing chronic persistent asthma (as per Australian Asthma Foundation guidelines) * Underlying medical conditions (eg cardiac disease) that increase the risks associated with anaphylaxis * Use of beta-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 * Already taking Probiotics
Outcome results
None listed