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.

项目总结-临床核心 在过去的15年里，约翰霍普金斯（JH）NIMH P30中心专注于进一步发现和 应用新的治疗方法来解决艾滋病毒相关的认知障碍，并成功地推进了 全球神经艾滋病研究。在此期间，临床核心不断发展，并保持纵向 一组特征明确的HIV感染者（PWH）和匹配的HIV未感染者的参与， 并成功地传播了丰富的表型临床和行为数据，生物标本， 超过50项NIH资助的研究，包括一项为期24周的鼻内胰岛素I/II期试点试验， 治疗HIV相关的神经认知障碍。从这些有价值的人类数据中，我们获得了至关重要的 深入了解中枢神经系统（CNS）系统功能障碍的异质性， 认知障碍以及情感（情绪，包括快感缺乏、社交退缩和焦虑）症状 和躯体症状（睡眠），沿着认知治疗反应的不同模式。我们还了解到 24周鼻内胰岛素与安慰剂相比改善了PWH的记忆力和注意力。作为回应，我们的团队 很早就转向了治疗开发的创新模式，即个性化医疗 方法开发和传播算法，患者数据驱动的方法，以最佳选择治疗 目标和预测PWH中的个体治疗反应。在2017年，核心走向指导上升 大数据协调和机器学习领域的领导者，扩大临床数据收集， 与情绪和焦虑症状相关的行为和自我报告指标，整合大脑测量，以及 包括对遗传禀赋、适应不良行为和生活经历的评估。通过这个 通过努力，临床核心是第一批利用NIMH研究领域标准（RDoC）的机构之一。 在NeuroHIV领域的框架，一种方法，将促进精确医学方法治疗 威尔斯亲王医院的神经精神并发症。在接下来的五年里，临床核心将与其他JH 核心和我们中心以外的人继续创新，成为NeuroHIV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。 在此框架下，我们的目标是：1）建立一个资源，提供丰富的表型临床数据， 支持CNS功能障碍的关键通路/回路的研究，并为治疗开发提供信息 2）为NeuroHIV学术界提供RDoC方面的咨询服务 实施，3）指导下一代NeuroHIV科学家与RDoC框架的整合， 及4）透过多项外展计划，让威尔斯亲王医院的社区参与及接受教育。