JHU Center for the Advancement of HIV Neurotherapeutics (JHU CAHN)- Clinical Core

JHU 艾滋病毒神经治疗促进中心 (JHU CAHN) - 临床核心

• 批准号: 10584559
• 负责人: Jennifer Marie Coughlin
• 金额: $ 31.45万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-06-16 至 2027-02-28
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10584559
• 关键词: AIDS clinical trial group; Acceleration; Address; Affective; Affective Symptoms; Algorithms; Anhedonia; Anxiety; Attention; Behavior assessment; Behavioral; Big Data; Bioinformatics; Brain; Caring; Central Nervous System; Charities; Clinical; Clinical Data; Clinical Trials; Cognition Disorders; Cognitive; Cohort Studies; Collaborations; Communities; Critical Pathways; Data; Data Analyses; Data Collection; Dedications; Endowment; Epidemiologist; Fright; Functional disorder; Funding; Genetic; Growth; HIV; HIV-associated neurocognitive disorder; Health Sciences; Heterogeneity; Image; Impaired cognition; Individual; Insulin; International; Knowledge; Laboratories; Learning; Life Experience; Machine Learning; Matched Group; Measurement; Measures; Memory; Mentors; Mentorship; Modeling; Molecular; Moods; National Institute of Mental Health; Patient Self-Report; Patients; Pattern; Persons; Phase; Phenotype; Placebos; Positioning Attribute; Postdoctoral Fellow; Psychiatrist; Research; Research Domain Criteria; Research Personnel; Resources; Scientist; Services; Sleep; Support Groups; Symptoms; System; Time; Underrepresented Minority; United States National Institutes of Health; Viral; Withdrawal; anxiety symptoms; clinical phenotype; cohort; data harmonization; data management; data quality; experience; human data; improved; innovation; insight; maladaptive behavior; mathematical model; member; mood symptom; multidimensional data; multidisciplinary; neuroAIDS; neuroimaging; neuropsychiatry; next generation; novel therapeutics; outreach program; personalized medicine; pilot trial; precision medicine; programs; response; social; student mentoring; therapeutic development; therapeutic target; therapeutically effective; treatment response

PROJECT SUMMARY – CLINICAL CORE Over the past 15 years, the Johns Hopkins (JH) NIMH P30 Center focused on furthering discovery and application of novel therapeutics to address HIV-associated Cognitive Disorders, and successfully advanced NeuroHIV research globally. During this time, the Clinical Core has grown and maintained longitudinal participation of a well-characterized cohort of people with HIV (PWH) and matched HIV-uninfected individuals, and successfully disseminated richly phenotyped clinical and behavioral data, biospecimens, and analytical expertise to over 50 NIH-funded studies, including a 24 week Phase I/II pilot trial of intranasal insulin for the treatment of HIV-associated neurocognitive disorder. From these valuable human data, we gained crucial insights into the heterogeneity of central nervous system (CNS) system dysfunction that manifests as varied cognitive impairments as well as affective (mood including anhedonia, social withdrawal & anxiety) symptoms and somatic symptoms (sleep), along with divergent patterns in cognitive treatment response. We also learned that 24 weeks of intranasal insulin vs. placebo improved memory and attention in PWH. In response, our group was early to pivot toward a new model of innovation in therapeutic development, namely a personalized medicine approach developing and disseminating algorithmic, patient data-driven approaches to best select therapeutic targets and predict individual treatment response in PWH. In 2017, the Core moved toward mentoring rising leaders in big data harmonization and machine learning, broadening the clinical data collection to capture behavioral and self-report metrics relevant to mood and anxiety symptoms, integrating brain measurements, and incorporating assessments of genetic endowment, maladaptive behaviors, and life experience. Through this effort, the Clinical Core was among the first to capitalize on the NIMH Research Domain Criteria (RDoC) framework in the NeuroHIV field, an approach that will facilitate precision medicine approaches to treating neuropsychiatric complications in PWH. Over the next five years, the Clinical Core will collaborate with other JH Cores and those outside our Center to continue to innovate as a critical resource in the NeuroHIV field. Specifically, the Clinical Core will support projects in target discovery, therapeutic development, and clinical trials. In the context of this framework, we aim to: 1) Establish a resource to provide richly phenotyped clinical data, to support the study of critical pathways/circuits underlying CNS dysfunction, and inform therapeutic development and application in PWH, 2) Provide consulting services to the academic NeuroHIV community in terms of RDoC implementation, 3) Mentor the next generation of NeuroHIV scientists with integration of the RDoC framework, and 4) Engage and educate the community of PWH through multiple outreach programs.

项目摘要 - 临床核心 在过去的15年中，约翰·霍普金斯（JH）NIMH P30中心着重于进一步的发现和 新型疗法的应用来解决与HIV相关的认知障碍，并成功进步 全球neurohiv研究。在此期间，临床核心增长和维持纵向 参与艾滋病毒（PWH）的人群良好的队列，并与艾滋病毒未感染的个体相匹配， 并成功传播了丰富的表型临床和行为数据，生物测量和分析 超过50项NIH资助的研究的专业知识，包括24周的I/II阶段试验性胰岛素试验试验 HIV相关神经认知障碍的治疗。从这些宝贵的人类数据中，我们获得了至关重要的 对中枢神经系统（CNS）系统功能障碍的异质性的见解，这种功能障碍表现为多样 认知障碍以及情感（包括Anhedonia，社交戒断和焦虑）符号 和躯体符号（睡眠），以及认知治疗反应中的不同模式。我们也学会了 鼻内胰岛素与安慰剂的24周改善了PWH中的记忆力和注意力。作为回应，我们的小组 很早就向理论发展中的新创新模式转移了，即一种个性化医学 方法开发和传播算法，患者数据驱动的方法最佳选择疗法 目标并预测PWH中的个体治疗反应。在2017年，核心朝着脑力复活迈进 大数据协调和机器学习的领导者，扩大临床数据收集以捕获 行为和自我报告指标与情绪和动画症状有关，整合大脑测量以及 纳入遗传捐赠，适应不良行为和生活经验的评估。通过这个 努力，临床核心是最早利用NIMH研究领域标准（RDOC）的核心之一。 Neurohiv领域的框架，这种方法将有助于治疗精确的医学方法 PWH中的神经精神并发症。在接下来的五年中，临床核心将与其他JH合作 核心和我们中心以外的核心继续创新，作为神经热领域的关键资源。 具体而言，临床核心将支持目标发现，治疗开发和临床试验的项目。 在此框架的背景下，我们的目标是：1）建立一种资源，以提供丰富的表型临床数据，以 支持CNS功能障碍的关键途径/电路的研究，并为治疗性开发提供信息 在PWH中的应用，2）根据RDOC为学术神经hiv社区提供咨询服务 实施，3）指导下一代神经hiv科学家，并通过RDOC框架整合， 4）通过多个外展计划参与和教育PWH社区。