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: 10475441
• 负责人: Leah Helane Rubin
• 金额: $ 32.26万
• 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/10475441
• 关键词: AIDS clinical trial group; Address; Affective; Affective Symptoms; Algorithms; Anhedonia; Attention; Behavior assessment; Behavioral; Big Data; Bioinformatics; Brain; Caring; Charities; Clinical; Clinical Data; Clinical Trials; Cognition Disorders; Cognitive; Cohort Studies; Communities; Consult; Critical Pathways; Data; Data Analyses; Data Collection; Endowment; Epidemiologist; Fright; Functional disorder; Funding; Genetic; Growth; HIV; HIV-associated neurocognitive disorder; Health Sciences; Heterogeneity; Image; Impaired cognition; Individual; Insulin; International; Knowledge; Laboratories; Life Experience; Machine Learning; Matched Group; Measurement; Measures; Memory; Mentors; Mentorship; Modeling; Molecular; Moods; National Institute of Mental Health; Neuraxis; 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; ranpirnase; 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 年里，约翰霍普金斯大学 (JH) NIMH P30 中心致力于进一步发现和 应用治疗小说来解决与艾滋病毒相关的认知障碍，并成功推进 在此期间，全球的 NeuroHIV 研究不断发展并保持纵向发展。 一组特征明确的艾滋病毒感染者（PWH）和匹配的未感染艾滋病毒的个体的参与， 并成功传播了丰富的表型临床和行为数据、生物样本和分析数据 超过 50 项 NIH 资助研究的专业知识，包括为期 24 周的鼻内胰岛素 I/II 期试点试验 从这些宝贵的人类数据中，我们获得了至关重要的治疗艾滋病毒相关的神经认知障碍的方法。 对中枢神经系统 (CNS) 系统功能障碍异质性的见解，其表现形式多种多样 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），以及认知治疗反应的不同模式。 与安慰剂相比，24 周的鼻内胰岛素改善了 PWH 的记忆力和注意力。 很早就转向治疗开发创新的新模式，即个性化医疗 方法开发和传播算法、患者数据驱动的方法来最佳选择治疗方法 2017 年，核心转向指导上升。 大数据协调和机器学习领域的领导者，扩大临床数据收集以捕获 与情绪和焦虑症状相关的行为和自我报告指标，整合大脑测量结果，以及 通过此评估结合遗传禀赋、适应不良行为和生活经历。 经过努力，临床核心是首批利用 NIMH 研究领域标准 (RDoC) 的项目之一 NeuroHIV 领域的框架，一种将促进精准医学治疗方法的方法 未来五年，临床核心将与其他 JH 合作。 核心人员和我们中心之外的人员将作为 NeuroHIV 领域的关键资源继续创新。 具体来说，临床核心将支持靶标发现、治疗开发和临床试验方面的项目。 在此框架的背景下，我们的目标是：1）建立资源来提供丰富的表型临床数据， 支持中枢神经系统功能障碍的关键通路/回路的研究以及治疗信息的开发 以及在PWH中的应用，2）为NeuroHIV学术界提供RDoC方面的咨询服务 实施，3) 通过整合 RDoC 框架指导下一代 NeuroHIV 科学家， 4) 通过多项外展计划吸引和教育感染者社区。