Enhancing Mobility in Older Adults by Treating Chronic Inflammation

通过治疗慢性炎症增强老年人的活动能力

• 批准号: 9520715
• 负责人: Jeremy D Walston
• 金额: $ 13.35万
• 依托单位: JOHNS HOPKINS UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2016
• 资助国家: 美国
• 起止时间: 2016-09-01 至 2019-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9520715
• 关键词: Adult; Aging; Anti-Inflammatory Agents; Anti-inflammatory; Biological; Biology; C-reactive protein; Catalogs; Chronic; Chronic Disease; Clinical Research; Clinical Trials; Clinical Trials Design; Country; Data; Data Analyses; Development; Doctor of Philosophy; Elderly; Epidemiologist; Etiology; Exclusion; Gait; Gait speed; Gluconates; Goals; Grant; Health; Heterogeneity; Home environment; Inflammation; Inflammatory; Interleukin-6; Intervention; Intervention Studies; Lactoferrin; Leadership; Link; Losartan; Maps; Measurement; Measures; Mediator of activation protein; Medical center; Methods; Michigan; Monitor; Multi-Institutional Clinical Trial; Nebraska; Nutrient; Oral; Outcome; Outcome Measure; Pathologic; Pharmacologic Substance; Pharmacy facility; Physical Function; Pilot Projects; Population; Population Study; Procedures; Protocols documentation; Randomized; Randomized Clinical Trials; Recruitment Activity; Registries; Research; Research Infrastructure; Research Personnel; Review Literature; Risk; Role; Sample Size; Seasons; Series; Serum; Signal Transduction; Site; Subgroup; Surface; Technology; Testing; TimeLine; Universities; Vermont; Walking; Women' s Health; Work; Zinc; base; biobank; cardiovascular health; data resource; design; effective intervention; evidence base; experience; frailty; functional outcomes; improved; improved mobility; indexing; inflammatory marker; innovation; intervention effect; mobility enhancement; mortality; novel; pilot trial; public health relevance; response; safety and feasibility; scale up; screening; secondary analysis; secondary outcome; sound; study population; successful intervention; treatment effect; treatment strategy; trial design

 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.

 描述（由应用提供）：由血清炎症标志物（例如C反应蛋白（CRP）和白介素6（IL-6）等长期升高所定义的慢性感染（CI）是已知的风险，即导致老年人，包括死亡率，脆弱，脆弱，慢性疾病和流动性的老年​​人健康状况的不良健康结果。尽管如此，关于如何 最好测量CI。由于老年人CI的异质性以及病因的复杂性，因此很少开发任何干预措施，这些干预措施专门针对CI和下游后果，例如迁移率下降。我们的总体假设指出，在几个月内降低炎症信号传导将降低血清炎症标志物水平并改善迁移率。为了在定义的临床试验中充分检验这一假设，必须确定大量有关感染与感染有关的信息。我们通过4个特定的目标提出，在患有CI的老年人中最终设计和实施了确定的多站点临床试验所需的团队和数据，该试验旨在通过抗炎治疗策略提高移动性。我们已经建立了一个经验丰富的合作研究团队，该团队在临床试验开发，慢性感染生物学，测量和分析，移动性测量和分析以及将老年人招募到临床研究方面具有专业知识。 PI，协调中心，制药分析团队和招聘站点将在约翰·霍普金斯大学举行。其他招聘地点将在密歇根大学，内布拉斯加州大学医学中心和杜克大学。这些站点是根据其招聘经验，老龄化研究注册表的可用性以及CI或流动性共同投资者的专业知识来选择的。在Russ Tracy博士的领导下，生物座位和测量核心将在佛蒙特大学举行。 Tracy博士在老年人人群研究中具有长期的CI测量专业知识。第一个目的是进一步发展和整合该团队和基础架构，以开发确定的多站点试验。 AIM 2旨在通过开发和完善迁移率和炎症测量，汇编设计和针对大规模CI干预的证据基础，并通过鉴定安全且潜在有效的抗炎药。 AIM 3旨在通过一系列口服抗炎剂的试点试验（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确定的试验基础设施，正式化招聘和测量程序，并确定安全有效的干预措施。最后，AIM 4阐明了该小组的路线图，朝着“铲铲”确定的临床试验，该试验将建立在研究团队和基础设施在3年时间表中开发的AIMS 2和3公元中产生的数据。在这项为期三年的研究结束时，编译的研究团队Full希望在准备实施的老年人中对CI和移动性进行确切的临床试验。