Study of induction of Tolerance to Oral Peanut: a randomized controlled trial of desensitisation using peanut oral immunotherapy in children (STOP II)

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We propose to study a new treatment for peanut allergy with the potential for major improvement in patient care. Peanut allergy is the commonest cause of fatal food-allergic reactions, population studies show it affects 2% of children, meaning tens of thousands of UK children are at risk. Spontaneous resolution is rare and patients are at risk of anaphylaxis and death. The perpetual fear and inconvenience surrounding restricted food choices and the requirement to carry emergency adrenaline injections at all times causes a significant reduction in quality of life. There is no treatment for this condition except to advise patients to avoid peanuts. With current practice up to 55% of children have accidental reactions every year, a significant number are severe and deaths occur. There is a clear need to develop a novel disease-modifying treatment. This is a definitive study of a new treatment based on a successful pilot study. This treatment could be made widely available across the NHS with considerable benefit for patients. We will recruit 104 peanut allergic subjects and allocate them to treatment and control groups using methods to reduce bias.The control group will be advised to avoid peanuts during a 5 month waiting period (i.e. the current standard practice).For the treatment group we will carefully administer increasing amounts of peanut flour by mouth over 5 months. Doses are increased every 2 weeks in hospital and the same doses taken daily at home. Subjects then receive a period of maintenance treatment with the highest dose for six weeks (appox. 5 peanuts). The main outcome measure is the proportion of subjects in each group who do not react to a peanut challenge test (i.e. the proportion iwhose allergy is 'cured'). Afterwards, to maintain a high ethical standard and encourage good compliance, after the waiting period, subjects in the control arm will also be offered the treatment. Other outcomes will be the change in quality of life score before and after intervention. Blood laboratory tests will be analysed throughout to define the mechanism of intervention, identify biomarkers which predict successful treatment and identify individuals in whom treatment is likely to be successful. The pilot study demonstrated success in all 18 subjects who have completed the protocol to date. It also showed that the daily home treatment is well tolerated and no severe reactions occurred. The families involved say the therapy has transformed their lives,reflected by increased quality of life scores. Publication of the initial results last month attracted enormous positive media attention and the study was covered by over 600 television, radio and newspaper articles world wide. Ethical considerations include the risk that the initial oral challenge will induce a unpleasant allergic reaction. However, we have taken many precautions to ensure that this does not occur (confirmed in our pilot study). This risk is balanced by the likelihood that enrolment in the study will confer a significant benefit to subjects, who may be able to eat peanut after treatment. We have obtained permission from the Local Research Ethics Committee to perform our pilot study which was of similar design. Our team is well placed to perform this research. Dr Pamela Ewan and Dr Andrew Clark have an excellent track record on delivering in clinical and laboratory Government funded research. Dr Clark conceived, initiated, designed and implemented the pilot study and led the current proposal. Our team have the necessary depth and breadth of expertise, all of whom have worked to complete the successful pilot study. Statistical design and analysis is provided by Dr Chris Palmer, Founding Director of the Institute of Medical Statistics in Cambridge. Results will be disseminated at scientific conferences, peer reviewed journals and via patient support groups. Major costs are for staff, consisting of a full time Clinical Fellow to perform the oral challenges and updo