Alzheimers Clinical Trials Consortium (ACTC)

总结。这是一个多PI应用程序，适用于U24合作协议，以开发最先进的 阿尔茨海默病临床试验联盟(ACTC)支持在全国范围内进行学术临床试验 阿尔茨海默病(AD)的连续体。这个ACTC将利用AD临床研究的深度和广度 南加州大学、哈佛大学和梅奥诊所的团队，以及35岁的研究人员的丰富经验 专家AD试验站点。我们的目标是创建优化的基础设施，以更高效地启动、快速招聘、 提高多样性，成功完成NIH支持的AD和相关痴呆的临床试验。我们 将利用简化的收缩流程，这是一个集中的IRB，专门关注神经退行性变 并纳入最先进的信息学和统计分析。我们建议加倍增加我们的 努力提高AD临床试验参与者的多样性，吸收我们最近 经验，并建立一个新的少数群体外联和招募(更多)团队，以支持中央 以及与有色人种社区的当地伙伴关系。我们将促进AD试验设计的持续创新， 提供有关新的认知、成像和生物标志物结果的专业知识，以支持未来的ACTC试验 申请。我们将评估在我们目前的试验中嵌入的有前景的探索性措施，例如Tau PET成像和计算机化认知测试，并努力将这些措施纳入稳健的 用于未来概念验证(POC)试验的平台，以快速评估疗效信号。我们提出了一个紧凑的 协调、分布式的领导模式，以创建真正的联盟并充分利用专业知识 跨多个机构。反恐协调中心将利用经验丰富的团队 南加州大学临床运营、数据系统和管理以及生物统计学。由梅奥领导的核磁共振小组， 由哈佛大学和加州大学伯克利分校领导的PET部门将利用无与伦比的多站点经验 通过ADNI、A4研究和多项正在进行的临床试验的方案。临床结果测定仪 Biomarkers Units将利用来自梅奥、哈佛和南加州大学的世界级专业知识来整合这两家公司 未来试验设计中的标准和新的结果衡量标准。该ACTC将提供专业知识和 基础设施，以设计和进行整个AD连续体系的试验，从初级预防举措到 晚期症状期的联合试验。我们也随时准备在其他年龄段合作进行试验- 相关痴呆症，利用哈佛大学NeuroNEXT团队和其他专家调查人员的经验 在血管和非阿尔茨海默病神经退行性疾病中。我们将在公共/私营部门取得成功的基础上再接再厉 并继续加强我们的战略联盟以进行大规模试验，但也将重点放在 支持研究人员发起的较小POC研究的新方法，以更好地为第三阶段提供信息 决策。最后，我们将为年轻的临床研究人员提供培训和领导机会，以 促进试验设计的持续创新，并催化下一代AD临床试验。

SUMMARY. This is a multi-PI application for the U24 Cooperative Agreement to develop a state-of-the-art Alzheimer Clinical Trial Consortium (ACTC) to support the conduct of academic clinical trials across the continuum of Alzheimer's disease (AD). This ACTC will leverage the depth and breadth of AD clinical research teams at USC, Harvard, and the Mayo Clinic, as well as the considerable experience of investigators at 35 expert AD trial sites. We aim to create an optimized infrastructure to more efficiently launch, rapidly recruit, improve the diversity, and successfully complete NIH supported clinical trials in AD and related dementias. We will utilize streamlined contracting processes, a centralized IRB with a specific focus on neurodegenerative diseases, and incorporate state-of-the-art informatics and statistical analyses. We propose to redouble our efforts to improve the diversity of participants in AD clinical trials, incorporating learnings from our recent experience, and establishing a new Minority Outreach and Recruitment (MORE) Team to support both central and local partnerships with communities of color. We will foster continued innovation in AD trial design, providing expertise on novel cognitive, imaging, and biomarker outcomes to support future ACTC trial applications. We will evaluate promising exploratory measures imbedded in our current trials, such as Tau PET imaging and computerized cognitive testing, and work to incorporate these measures into a robust platform for future Proof of Concept (POC) trials to rapidly assess signals of efficacy. We propose a tightly coordinated, distributed leadership model to create a true consortium and take full advantage of the expertise across multiple institutions. The ACTC Coordinating Center will leverage the highly experienced teams in Clinical Operations, Data Systems and Management, and Biostatistics at USC. The MRI Unit, led by Mayo, and PET Unit, led by Harvard and UC Berkeley, will capitalize on unparalleled experience with multi-site protocols through ADNI, the A4 Study, and multiple ongoing clinical trials. The Clinical Outcome Instrument and Biomarkers Units will leverage world-class expertise from Mayo, Harvard, and USC to incorporate both standard and novel outcome measures in future trial designs. This ACTC will provide expertise and infrastructure to design and conduct trials across the full continuum of AD, from primary prevention initiatives to combination trials for advanced symptomatic stages. We also stand ready to collaborate on trials in other age- related dementias, leveraging the experience of the NeuroNext team at Harvard and other expert investigators in vascular and non-AD neurodegenerative diseases. We will build on our successes with public/private partnerships and continue to strengthen our strategic alliances to conduct large scale trials, but will also focus on supporting novel approaches to smaller investigator-initiated POC studies that will better inform Phase 3 decision-making. Finally, we will provide training and leadership opportunities to young clinical investigators to facilitate continued innovation in trial design, and catalyze the next generation of AD clinical trials.