DIAN-TU Primary Prevention Trial

DIAN-TU一级预防试验

• 批准号: 9782832
• 负责人: Eric Martin McDade
• 金额: $ 1769.58万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2018
• 资助国家: 美国
• 起止时间: 2018-09-15 至 2025-05-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/9782832
• 关键词: Abeta synthesis; Address; Alzheimer' s Disease; Alzheimer' s disease pathology; Alzheimer' s disease risk; Alzheimer’s disease biomarker; Amyloid; Amyloid beta-Protein; Amyloid beta-Protein Precursor; Amyloid deposition; Amyloidosis; Biological Markers; Blinded; Clinical; Clinical Trials; Cognitive; Consensus; Country; Dementia; Detection; Development; Disease; Disease Progression; Double-Blind Method; Down Syndrome; Enrollment; Evolution; Foundations; Funding; Future; Gene Proteins; Goals; Grant; Health; Health Benefit; Impaired cognition; Individual; Infrastructure; Inherited; Intervention; Language; Measures; Mutation; Neuronal Dysfunction; Outcome Study; Participant; Pathologic; Pathology; Pharmaceutical Preparations; Phase; Placebos; Population; Positioning Attribute; Positron-Emission Tomography; Presenile Alzheimer Dementia; Prevention; Prevention trial; Primary Prevention; Prior Therapy; Production; Public Health; Randomized; Risk; Role; Secondary Prevention; Senile Plaques; Site; Symptoms; Testing; Therapeutic; Therapeutic Intervention; Therapeutic Trials; Time; Uncertainty; Vulnerable Populations; Work; abeta accumulation; abeta deposition; amyloid pathology; arm; base; beta amyloid pathology; blind; cerebral atrophy; cognitive benefits; comorbidity; design; effective intervention; effective therapy; mutation carrier; neuron loss; operation; prevent; prevention clinical trial; randomized placebo controlled study; success; tau-1; treatment arm

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.

项目摘要 DIAN-TU平台的形成是为了设计和管理介入治疗试验， 为那些肯定会发展为显性遗传性AD（DIAD）的人提供认知益处的治疗。的 DIAN-TU试验平台目前已在6个国家和24个研究中心全面运行，另外13个国家和26个研究中心也已全面运行。 网站在启动目前的DIAN-TU-001试验将支持11种语言， 在二级预防中测试的治疗（即认知正常的严重AD受试者） 病理学）。NIA为DIAN-TU试验平台提供的资金建立了基础设施和运营， 在DIAD中执行临床试验，并认识到在该平台内发展的必要性。 DIAN-TU一级预防试验是同类试验中的第一项，II/III期，4年随机，设盲 在160例无症状显性遗传性阿尔茨海默病突变携带者中进行的安慰剂对照（1：1）试验 在估计的症状发作年（EYO）之前超过15年，并且患有最低限度或无哮喘的患者， 试验入组时的PiB斑块负荷。目前在无症状个体中进行的试验靶向病理学检查后的Ablation。 建立;这些二级预防工作可能比治疗更有效， 然而，最有效的方法是防止AD病理形成。的目标 该提案旨在实施针对淀粉样蛋白的安慰剂对照生物标志物终点临床试验， 在有DIAD风险的受试者中，在显著的AAD病理学发作之前， 在这项研究中，我们将测试是否有可能防止DIAD突变携带者的ARAPINE沉积，如果这样做， 将预防与AD相关的病理级联，并最终在人群中预防痴呆， 否则肯定会得这种病无论这项研究的结果如何，它都将对 AD领域评估预防淀粉样变性的能力和最早这样做的后果 AD病理级联的阶段。如果在DIAD中预防了ARAPINE病理学， 为淀粉样蛋白假说的最终测试奠定了基础，并提供了最好的机会来证明， 在这个高度脆弱的人群中，可能在散发性AD和唐氏综合征中， 戏剧性的修改。预防淀粉样病变的发展是否对 这种疾病，特别是在这一人群中，这将指导未来的研究和治疗， 机制和病理。