DIAN-TU Primary Prevention Trial

项目总结 DIAN-TU平台的成立是为了设计和管理介入治疗试验，并找到一个 为那些肯定会发展为显性遗传性阿尔茨海默病(DIAD)的人提供认知益处的治疗。这个 Dian-TU试验平台现已在6个国家和24个地点全面运营，另外还有13个国家和26个国家 初创阶段的网站。目前的DIAN-TU-001试用版将支持11种语言，并有三种不同的 二级预防中正在测试的治疗方法(即认知正常的阿尔茨海默病患者 病理学)。NIA为DIAN-TU试验平台提供的资金为 在DIAD中执行临床试验，并承认在这一平台内发展的必要性。 DIAN-TU初级预防试验是第一个此类试验，II/III阶段，为期4年，随机、盲法 160例无症状显性遗传性阿尔茨海默病突变携带者的安慰剂对照(1：1)试验 他们在估计的症状出现年(Eyo)之前15年以上，并且有极小的或没有A？ 试验进入时的PIB斑块负担。目前在无症状个体中的试验是在病理后以A？为靶点 这些二级预防措施可能比以后更多的治疗更有效 然而，最有效的方法是防止AD病理的形成。的目标是 这项建议是实施一项针对淀粉样蛋白的安慰剂对照生物标记物终点临床试验 有DIAD风险的受试者，在出现明显的A？病理之前，有沉积现象。 在这项研究中，我们将测试是否有可能防止DIAD突变携带者中的A？沉积，如果这样做了 将防止与AD相关的病理级联，并最终在一个 否则肯定会得这种病。无论这项研究的结果如何，它都将对 在AD领域评估预防淀粉样变性的能力和尽早这样做的后果 阿尔茨海默病病理级联的各个阶段。如果在DIAD中预防A？病理是成功的，它将奠定 最终检验淀粉样蛋白假说的基础，并提供了证明这一点的最佳机会 在这一高度脆弱的人群中，痴呆症，可能在散发性AD和唐氏综合症中，可以 戏剧性的改装。预防淀粉样蛋白病变的发展是否对糖尿病的进程没有影响 这种疾病，特别是在这个人群中，这将引导未来的研究和治疗转向其他 机制和病理学。

PROJECT SUMMARY The DIAN-TU platform was formed to design and manage interventional therapeutic trials and find a treatment that provides cognitive benefit for those certain to develop dominantly inherited AD (DIAD). The DIAN-TU trial platform is now fully operational in 6 countries and 24 sites with another 13 countries and 26 sites in start-up. The current DIAN-TU-001 trial will accommodate 11 languages and has three different therapies being tested in secondary prevention (i.e. cognitively normal participants with substantial AD pathology). NIA funding for the DIAN-TU trial platform established the infrastructure and operations for executing clinical trials in DIAD and acknowledged the need for evolution within this platform. The DIAN-TU Primary Prevention Trial is a first of its kind, phase II/III, 4-year randomized, blinded placebo-controlled (1:1) trial in 160 asymptomatic dominantly inherited Alzheimer disease mutation carriers who are more than 15 years before the estimated year of symptom onset (EYO) and have minimal to no Aß- PiB plaque burden at trial entry. Current trials in asymptomatic individuals target Aß after pathology is established; these secondary prevention efforts are likely more effective than treating at later more advanced stages, however the most effective approach is to prevent AD pathology from forming. The goal of this proposal is to implement a placebo controlled biomarker endpoint clinical trial targeting amyloid deposition in subjects at risk for DIAD, prior to onset of significant Aß pathology. In this study, we will test if it is possible to prevent Aß deposition in DIAD mutation carriers and if doing so will prevent the cascade of pathology associated with AD and, ultimately, dementia in a population that is otherwise certain to get the disease. Regardless of the outcome of this study, it will be highly impactful on the AD field in assessing the ability to prevent amyloidosis and the consequences of doing so at the earliest stages of the AD pathological cascade. If the prevention of Aß pathology in DIAD is accomplished, it will lay the foundation for the ultimate test of the amyloid hypothesis and provide the best opportunity to prove that dementia in this highly vulnerable population, and possibly in sporadic AD and Down syndrome, can be dramatically modified. Should preventing amyloid pathology from developing have no impact on the course of the disease, particularly in this population, this would direct future research and therapeutics towards other mechanisms and pathologies.