Dominantly Inherited Alzheimer's Network Trials Unit - Adaptive Prevention Trial

描述：常染色体显性遗传性阿尔茨海默病(AD)向AD研究领域提供了进一步的分子和生化机制，这些机制被认为是常染色体显性AD突变的病理基础，提供了动物和细胞模型，用于开发抗阿司匹林药物。常染色体显性阿尔茨海默病的预防试验可能是预防所有形式阿尔茨海默病的先驱。这项建议是正在进行的第二阶段遗传性阿尔茨海默病网络试验单元(DIAN TU)生物标记物试验中领先的淀粉样β修改治疗的第三阶段关键认知终点试验，旨在防止常染色体占主导地位的AD人群中的认知丧失。结果--将推进在普通人群中寻找替代生物标记物和预防AD的途径。如果这一单一的3期试验呈阳性，它可能会导致一种用于预防的疾病修饰药物获得批准。DIAN-TU与补充阿尔茨海默病预防倡议(API)和无症状AD的ADCS抗淀粉样蛋白治疗(A4)建立了阿尔茨海默氏症预防合作(CAP)，以确保过程高效，公共资金物有所值，结果将推动整个领域的发展。DIAN TU建立了DIAN扩展登记处(www.DIANXR.org)，并确定了更多潜在的D-IAN-TU试验地点，通过将参与者人数增加到3,000多人，使更大规模的第三阶段预防试验得以进行。第一项预防试验，即第二阶段生物标记物试验，针对常染色体显性AD风险人群，于2012年12月启动。DIAN-TU适应性预防试验(APT)利用DIAN观察性研究和DIAN-TU的现有基础设施，从相关站点招募DIAN-TU参与者以及常染色体显性AD风险人群。点图APT是DIAN观测研究的合乎逻辑的下一步。患者是有动力的，因为这项试验是大多数人在数十年的研究参与后遇到的第一个具体希望。这项试验设计是一项随机、双盲安慰剂对照的双臂试验，在266名(每臂133名)无症状常染色体显性AD突变携带者中，选择表现最好的安全性、耐受性和生物标记物疗效最佳的纤维抗Aü抗体、可溶性抗Aü抗体或β-分泌酶抑制剂。受试者将接受为期四年的药物或安慰剂治疗，以确定中枢神经系统作用机制和下游AD生物标记物的临床和认知利益参与。药物组将与安慰剂组进行比较，CDR总和的主要结果和认知测量、计算机化的认知电池、安全性和AD生物标记物的次要结果。

DESCRIPTION: Autosomal dominant Alzheimer's disease (AD) has informed the field of AD research about the - Further, molecular and biochemical mechanisms that are believed to underlie the athological basis of AD mutations from autosomal dominant AD have provided animal and cellular models that are utilized to develop anti-Aß drugs. Prevention trials of autosomal dominant AD are likely to pioneer approaches for prevention - trials for all forms of AD. This proposal for a phase 3 pivotal cognitive endpoint trial of the leading amyloid- - beta modifying treatment from the ongoing phase 2 Dominantly Inherited Alzheimer's Network - Trial Unit (DIAN TU) biomarker trial aims to prevent cognitive loss in the autosomal-dominant AD population. Results - will advance the search for surrogate biomarkers and for a pathway to preventing AD in the general population. If this single phase 3 trial is positive, it may lead to te approval of a disease modifying drug for prevention. The DIAN-TU has founded the Collaboration for Alzheimer's Prevention (CAP) with the complementary-Alzheimer Prevention Initiative (API) and the ADCS Anti Amyloid treatment in Asymptomatic AD (A4) to ensure processes are efficient, public dollars are well spent, and results will advance the entire field. The DIAN TU established the DIAN Expanded Registry (www.DIANXR.org) and identified additional potential D-IAN-TU trial sites to enable the larger phase 3 prevention trial by increasing the number of participants to more than 3,000. The first prevention trial, a phase 2 biomarker trial, for people at risk of autosomal dominant AD was launched in December, 2012. The DIAN-TU Adaptive Prevention Trial (APT) leverages the existing infrastructure of the DIAN observational study and the DIAN-TU, and enrolls DIAN-TU participants as well as people at risk of autosomal dominant AD from associated sites. The DIANTU APT is the logical next step of the DIAN observational study. The patients are motivated, as this trial is the first concrete hope most have encountered after decades of research participation. The trial design is a randomized, double-blinded placebo controlled two arm trial of the selected best performing safety, tolerability and biomarker efficacy fibrillar anti-Aß antibody, a soluble anti-Aß antibody,or a beta-secretase inhibitor in 266 (n=133 per arm) asymptomatic autosomal dominant AD mutation carriers. Subjects will receive either drug or placebo for four years to determine clinica and cognitive benefit engagement of the CNS mechanism of action and downstream AD biomarkers. The drug arm will be compared to the placebo arm with the primary outcome of CDR Sum-of-Boxes and secondary outcomes of cognitive measures, computerized cognitive battery, safety, and AD biomarkers.