Enhancing Mobility in Older Adults by Treating Chronic Inflammation

 描述(由申请人提供)：慢性炎症(CI)由血清炎症标记物如C-反应蛋白(CRP)和白介素6(IL-6)的慢性升高定义，是老年人发展不良健康结果的已知风险，包括死亡率、虚弱、慢性病和活动能力下降。尽管如此，人们对此知之甚少。 最好测量CI。由于老年人CI的异质性和病因的复杂性，几乎没有开发出专门针对CI和下游后果(如行动能力下降)的干预措施。我们的主要假设是，在几个月的时间里减少炎症信号将降低血清炎症标记物的水平，并改善流动性。为了在权威的临床试验中充分验证这一假设，必须确定与炎症、流动性和抗炎干预相关的大量信息。我们建议，通过4个具体目标，发展团队和必要的数据，以最终设计和实施一项针对老年CI患者的明确的、多地点的临床试验，旨在通过抗炎治疗策略改善行动能力。我们建立了一支经验丰富的协作研究团队，在临床试验开发、慢性炎症生物学、测量和分析、流动性测量和分析以及招募老年人参与临床研究方面拥有专业知识。PI、协调中心、药房分析团队和招聘地点将设在约翰·霍普金斯大学。其他招聘地点将在密歇根大学、内布拉斯加大学医学中心和杜克大学。这些网站是根据他们的招聘经验、老龄化研究登记的可用性以及CI或流动性方面的合作调查人员的专业知识而选择的。生物仓库和测量核心将在佛蒙特州大学由Russ Tracy博士领导。特雷西博士在老年人人口研究中的CI测量方面拥有长期的专业知识。第一个目标是进一步发展和整合这一团队和开发最终多点试验所需的基础设施。AIM 2旨在通过开发和改进流动性和炎症测量，汇编用于设计和定位大规模CI干预的证据基础，以及通过识别安全和潜在有效的抗炎药，为CI和流动性提供明确的临床试验设计。AIM 3旨在通过一系列口服抗炎剂的试点试验，为最终的临床试验设计提供信息，包括 乳铁蛋白、葡萄糖酸锌和氯沙坦。这些试点研究将有助于建立最终的试验基础设施，正式确定招募和衡量程序，并确定安全和潜在有效的干预措施。最后，目标4阐明了该小组的路线图，以建立在目标2和目标3中关于研究团队的数据和在3年时间线内开发的基础设施的基础上，进行一项“准备好铲”的最终临床试验。在这项为期3年的研究结束时，汇编的研究团队Full预计将有一项针对老年人CI和活动能力的明确临床试验，准备实施。

 DESCRIPTION (provided by applicant): Chronic inflammation (CI) as defined by chronic elevation in serum inflammatory markers such as C-reactive protein (CRP) and Interleukin-6 (IL-6) is a known risk for the development of adverse health outcomes in older adults, including mortality, frailty, chronic disease, and mobility declines. Despite this, little is known about how best to measure CI. Because of the heterogeneity of CI in older adults, and complexity of etiology, few if any interventions have been developed that specifically target CI and downstream consequences such as mobility decline. Our overarching hypothesis states that decreasing inflammatory signaling over a period of several months will decrease serum levels of inflammatory markers and improve mobility. In order to adequately test this hypothesis in a definitive clinical trial, a great deal of information related in inflammation, mobility and anti- inflammatory interventions must be determined. We propose, through 4 specific aims, to develop the team and data necessary to ultimately design and implement a definitive, multi-site clinical trial in older adults with CI that aims to improve mobility through anti-inflammatory treatment strategies. We have established a highly experienced collaborative research team with expertise in clinical trials development, chronic inflammation biology, measurement, and analysis, mobility measurement and analysis, and recruitment of old adults into clinical studies. The PI, coordinating center, pharmacy analytical team, and recruitment site will be at Johns Hopkins University. Other recruitment sites will be at the University of Michigan, University of Nebraska Medical Center, and Duke University. These sites were chosen based on their recruitment experience, availability of aging research registry, and expertise of co-investigators in CI or mobility. The Biorepository and Measurement Core will be at the University of Vermont under the leadership of Russ Tracy, PhD. Dr. Tracy has long standing expertise in CI measurement in population studies of older adults. The first aim is to further develop and integrate this team and infrastructure necessary to develop a definitive multisite trial. Aim 2 is designed to inform a definitive clinical trial design on CI and mobility through the development and refinement of mobility and inflammatory measurements, compilation of an evidence base on which to design and target a large-scale CI intervention, and through the identification of safe and potentially effective anti-inflammatory agents. Aim 3 was designed to inform a definitive clinical trial design through a series of pilot trials of oral anti- inflammatory agents, including lactoferrin, zinc gluconate, and losartan. These pilot studies will help to develop the definitive trial infrastructure, formalize recruitment and measurement procedures, and identify safe and potentially effective interventions. Finally, Aim 4 articulates the group's road map towards a `shovel ready' definitive clinical trial that will be built on the data generated in aims 2 and 3 ad on the study team and infrastructure developed during the 3 year timeline. At the end of this 3 year study, the compiled research team full expects to have a definitive clinical trial of CI and mobility in older adults ready for implementation.