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

口服花生耐受诱导研究：儿童花生口服免疫疗法脱敏的随机对照试验（STOP II）

• 批准号: MC_G1002461
• 负责人: Andrew Clark
• 金额: $ 85.53万
• 依托单位: University of Cambridge
• 依托单位国家: 英国
• 项目类别: Intramural
• 财政年份: 2010
• 资助国家: 英国
• 起止时间: 2010 至 无数据
• 项目状态: 已结题
• 来源: https://gtr.ukri.org/projects?ref=MC_G1002461
• 关键词: Study; induction; Tolerance; Oral; Peanut

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

我们建议研究一种治疗花生过敏的新方法，这可能会大大改善患者的护理。花生过敏是致命食物过敏反应最常见的原因，人口研究表明，2%的儿童受到影响，这意味着成千上万的英国儿童处于危险之中。自发性消退是罕见的，患者有过敏反应和死亡的危险。限制食物选择带来的永久恐惧和不便，以及随时需要紧急注射肾上腺素的要求，导致生活质量显著下降。对于这种情况，除了建议患者避免食用花生之外，没有任何治疗方法。按照目前的做法，每年有多达55%的儿童发生意外反应，其中相当一部分是严重的，并发生死亡。很明显，我们需要开发一种新的治疗疾病的方法。这是一项基于成功的初步研究的新疗法的明确研究。这种治疗可以在整个NHS中广泛使用，对患者有相当大的好处。我们将招募104名花生过敏受试者，按照减少偏倚的方法将其分为治疗组和对照组。对照组将被建议在5个月的等待期内避免食用花生（即目前的标准做法）。对于实验组，我们将在5个月的时间里小心地增加花生粉的口服量。在医院每两周增加一次剂量，在家中每天服用相同剂量。然后受试者以最高剂量接受为期六周的维持治疗（appox）。5花生)。主要结果衡量指标是每组中对花生刺激试验无反应的受试者比例（即过敏被“治愈”的比例）。之后，为了保持较高的道德标准并鼓励良好的依从性，在等待期后，对照组的受试者也将接受治疗。其他结果将是干预前后生活质量评分的变化。将对血液实验室测试进行全程分析，以确定干预机制，确定预测治疗成功的生物标志物，并确定治疗可能成功的个体。试点研究表明，迄今为止完成方案的所有18名受试者都取得了成功。研究还表明，日常家庭治疗耐受性良好，未发生严重反应。参与治疗的家庭表示，这种疗法改变了他们的生活，生活质量得分的提高反映了这一点。上个月公布的初步结果引起了媒体的极大积极关注，全世界有600多篇电视、广播和报纸报道了这项研究。伦理方面的考虑包括最初的口服挑战会引起不愉快的过敏反应的风险。然而，我们已经采取了许多预防措施来确保这种情况不会发生（在我们的试点研究中得到证实）。这种风险被纳入研究将给受试者带来显著益处的可能性所平衡，他们在治疗后可能能够吃花生。我们已经获得了当地研究伦理委员会的许可，可以进行类似设计的试点研究。我们的团队很适合进行这项研究。Pamela Ewan博士和Andrew Clark博士在政府资助的临床和实验室研究中有着出色的记录。克拉克博士构思、发起、设计和实施了这项试点研究，并领导了目前的提案。我们的团队拥有必要的深度和广度的专业知识，他们都曾努力完成成功的试点研究。统计设计和分析由剑桥医学统计研究所创始主任克里斯·帕尔默博士提供。研究结果将在科学会议、同行评议期刊和患者支持小组上传播。主要费用用于员工，包括一名全职临床研究员进行口腔挑战和盘发

项目成果

Assessing the efficacy of oral immunotherapy for the desensitisation of peanut allergy in children (STOP II): a phase 2 randomised controlled trial.

• DOI: 10.1016/s0140-6736(13)62301-6
• 发表时间: 2014-04-12
• 期刊: LANCET
• 影响因子: 168.9
• 作者: Anagnostou, Katherine;Islam, Sabita;King, Yvonne;Foley, Loraine;Pasea, Laura;Bond, Simon;Palmer, Chris;Deighton, John;Ewan, Pamela;Clark, Andrew
• 通讯作者: Clark, Andrew