DOMINANTLY INHERITED ALZHEIMER NETWORK TRIAL: AN OPPORTUNITY TO PREVENT DEMENTIA

显性遗传性阿尔茨海默病网络试验：预防痴呆症的机会

• 批准号: 9111783
• 负责人: RANDALL J BATEMAN
• 金额: $ 150万
• 依托单位: WASHINGTON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2013
• 资助国家: 美国
• 起止时间: 2013-09-20 至 2020-06-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9111783
• 关键词: Accounting; Alzheimer disease prevention; Alzheimer' s Disease; Amyloid; Amyloid beta-Protein Precursor; Animal Model; Antibodies; Antibody Formation; Atrophic; Biochemical; Biological; Biological Markers; Blinded; Blood; Brain; Cell model; Cerebrospinal Fluid; Chronic; Clinical; Clinical Trials; Clinical Trials Design; Cognitive; Collection; Cross-Sectional Studies; Data Set; Dementia; Development; Disease; Enrollment; Functional disorder; Funding; Future; Genes; Goals; Grant; Health; Image; Impaired cognition; Individual; Inherited; Interest Group; International; Liquid substance; Metabolic; Modification; Molecular; Monoclonal Antibodies; Mutation; Nature; Nerve Degeneration; Onset of illness; Oral; Outcome; Participant; Patients; Performance; Pharmaceutical Preparations; Pharmacologic Substance; Phase; Phenotype; Placebo Control; Placebos; Population; Positron-Emission Tomography; Prevention trial; Probability; Process; Production; Protocols documentation; Randomized; Recruitment Activity; Registries; Research; Research Infrastructure; Risk; Staging; Symptoms; Testing; Therapeutic; Time; United States National Institutes of Health; amyloid imaging; arm; autosomal dominant mutation; base; beta secretase; beta-site APP cleaving enzyme 1; brain volume; cerebral amyloidosis; design; drug testing; effective therapy; four-arm trial; glucose metabolism; imaging biomarker; improved; inhibitor/antagonist; injection/infusion; meetings; mutation carrier; presenilin-1; presenilin-2; prevent; primary outcome; randomized placebo controlled trial; response; secondary outcome; tau Proteins; therapeutic effectiveness; treatment group; trial design

DESCRIPTION (provided by applicant): Autosomal dominant Alzheimer's disease (AD) has informed the field of AD research about the molecular and biochemical mechanisms that are believed to underlie the pathological basis of AD. Further, mutations from autosomal dominant AD have provided animal and cellular models that are utilized to develop anti-A� drugs. Due to the rarity of autosomal dominant AD, the Dominantly Inherited Alzheimer Network (DIAN; U01 AG032438) was launched in 2008 to establish an international, multicenter registry of individuals at risk or with a known causative mutation of AD in the amyloid precursor protein (APP), presenilin 1 (PS1), or presenilin 2 (PS2) genes. DIAN evaluates participants at entry and longitudinally thereafter with clinical and cognitive batteries, structural, functional, metabolic,and amyloid imaging protocols, and biological fluid (blood; cerebrospinal fluid) collection with the goal of determining the sequence of imaging and biomarker changes in presymptomatic gene carriers who are destined to develop AD. Because the clinical and pathological phenotypes of dominantly inherited AD appear similar to those for the far more common late-onset "sporadic" AD, the nature and sequence of brain changes in dominantly inherited AD are also likely relevant for sporadic AD. The trial design is a randomized, blinded placebo controlled four arm trial of a fibrillar anti-A� antibody, a soluble anti-A� antibody, and a beta-secretase inhibitor i 160 (n=40 per arm) asymptomatic to mildly symptomatic ADAD mutation carriers. Subjects will receive either drug of placebo for two years to determine engagement of the CNS mechanism of action and downstream AD biomarkers.

描述（由适用提供）：常染色体显性阿尔茨海默氏病（AD）已将AD研究领域告知有关分子和生化机制，这些机制被认为是AD病理基础的基础。此外，常染色体显性AD的突变提供了用于开发抗A药物的动物和细胞模型。由于常染色体显性广告的稀有性，2008年启动了主要继承的阿尔茨海默氏症网络（Dian; U01 AG032438），以建立一个具有风险或已知严重AD的个体的多中心注册表，该注册表中已知的AD的严重突变在淀粉样蛋白前体蛋白（App），Presenililin 1（Ps1）（PS1）（PS1），或PSENILIN 2（PS1）2（PS1）2（PS1）2（PS1）2（PSENILIN 2（PSENILIN 2）。戴安（Dian）在进入和纵向上的参与者之后，通过临床和认知电池，结构，功能，代谢和淀粉样蛋白成像方案以及生物学液（血液；脑脊液）收集的目的是确定成像和生物标志物在预性基因中的序列变化的序列。由于主要遗传AD的临床和病理表型似乎与更常见的晚期发作的“零星” AD相似，因此大脑变化的性质和序列主要遗传的AD可能与零星的AD有关。该试验设计是一项随机，盲目的安慰剂对照的四臂试验，该试验的纤维抗A，固体抗A和β-分泌酶抑制剂I 160（n = 40 n = 40）渐变为轻度症状的ADAD突变携带者。受试者将接受两年的安慰剂药物，以确定CNS作用机理和下游AD生物标志物的参与。