Enhancing Mobility in Older Adults by Treating Chronic Inflammation: Pilot Phase

 描述（由申请人提供）：慢性炎症（CI）定义为血清炎症标志物（如C反应蛋白（CRP）和白细胞介素-6（IL-6））的慢性升高，是老年人发生不良健康结局（包括死亡、虚弱、慢性疾病和活动能力下降）的已知风险。尽管如此，人们对如何做到这一点知之甚少。 最好的方法是测量CI。由于CI在老年人中的异质性和病因的复杂性，很少有干预措施专门针对CI和下游后果，如流动性下降。我们的总体假设表明，在几个月的时间内减少炎症信号将降低炎症标志物的血清水平并改善流动性。为了在确定的临床试验中充分地测试该假设，必须确定与炎症、移动性和抗炎干预相关的大量信息。我们建议，通过4个具体的目标，开发必要的团队和数据，最终设计和实施一个明确的，多中心的临床试验，在老年人CI，旨在通过抗炎治疗策略，以提高流动性。我们建立了一支经验丰富的合作研究团队，在临床试验开发，慢性炎症生物学，测量和分析，移动性测量和分析以及招募老年人参与临床研究方面具有专业知识。主要研究者、协调中心、药学分析团队和招募中心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。这些研究中心的选择是基于其招募经验、老龄化研究登记的可用性以及共同研究者在CI或流动性方面的专业知识。生物储存和测量核心将在佛蒙特大学的Russ Tracy博士的领导下进行。Tracy博士在老年人人口研究中的CI测量方面具有长期的专业知识。第一个目标是进一步发展和整合这个团队和基础设施，以开发一个确定的多中心试验。目的2旨在通过开发和完善流动性和炎症测量，汇编设计和靶向大规模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。目的3旨在通过一系列口服抗炎药的先导性试验，为确定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开发明确的试验基础设施，正式确定招募和测量程序，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“准备好铲”的最终临床试验为基础，该试验将建立在目标2和3中产生的数据之上，研究团队和基础设施在3年时间轴内开发。在这项为期3年的研究结束时，编制的研究团队完全期望在老年人中进行CI和移动性的确定性临床试验。

 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.