The ENRGISE Study

 描述（由申请人提供）：来自我们小组和其他人的越来越多的证据表明，以血浆C反应蛋白、肿瘤坏死因子α，特别是白细胞介素-6（IL-6）升高为特征的低度慢性炎症是残疾、活动能力受损和步行速度降低的独立风险因素。低度慢性炎症是一个可改变的风险因素。然而，目前尚不清楚降低炎症标志物水平的干预措施本身是否能改善老年人的活动能力，或避免老年人活动能力的下降。 为了解决这一证据差距，我们提出了随机临床试验ENRGISE（使SEniors的低度炎症减少），以测试抗炎干预措施通过改善或保留行走能力来预防严重移动性残疾的能力。我们通过选择对弱势老年人来说安全、可容忍、可接受和负担得起的干预措施，最大限度地扩大了我们拟议干预措施的公共卫生影响。基于广泛的文献综述，我们建议测试血管紧张素受体阻滞剂氯沙坦和鱼油形式的ω-3多不饱和脂肪酸单独和联合治疗与安慰剂相比的疗效。血管紧张素受体阻滞剂和ω-3多不饱和脂肪酸在临床试验中均显示出降低IL-6，初步数据表明它们可能改善身体功能。 我们计划招募老年人谁是风险，或与，行动障碍，衡量缓慢的步态速度和自我报告的行动困难，谁有升高的水平IL-6，标志物最一贯与行动限制。在有效设计和执行这种试验之前，需要收集关于可行性的初步数据。我们建议进行一个可行性阶段，包括对现有试验和队列进行荟萃分析，并进行一项试点试验，以评估干预措施对几种炎症标志物和步行速度的影响。这将使我们能够完善ENRGISE主要试验的设计、招募率、目标人群、依从性、保留率、耐受性、样本量和成本。我们将组装ENRGISE试点和主要试验所需的多中心研究基础设施，包括生物储存库，我们将开发实施试验所需的材料，包括方案，操作手册，数据和安全监测计划，表格，质量控制和质量保证计划，以及招募和保留材料。

 DESCRIPTION (provided by applicant): Growing evidence from our group and others shows that low-grade chronic inflammation, characterized by elevations in plasma C-reactive protein, tumor necrosis factor alpha, and particularly Interleukin-6 (IL-6), is an independent risk factor o disability, impaired mobility, and lower walking speed. Low-grade chronic inflammation is a modifiable risk factor. However, it is unknown whether interventions that reduce the levels of inflammatory markers per se improve mobility, or avert decline in mobility in older persons. To address this gap in evidence we propose the randomized clinical trial ENRGISE (ENabling Reduction of low-Grade Inflammation in SEniors) to test the ability of anti-inflammatory interventions for preventing major mobility disability by improving or preserving walking ability. We have maximized the public health impact of our proposed interventions by selecting interventions that are safe, tolerable, acceptable, and affordable for vulnerable older persons. Based on an extensive literature review, we propose to test the efficacy vs. placebo of the angiotensin receptor blocker losartan and omega-3 polyunsaturated fatty acids in the form of fish oil, alone and in combination. Both angiotensin receptor blockers and omega-3 polyunsaturated fatty acids have shown to reduce IL-6 in clinical trials and preliminary data suggest that they may improve physical function. We plan to recruit older persons who are at risk for, or with, mobility impairment, as measured by slow gait speed and self-reported mobility difficulty, and who have elevated levels of IL-6, the marker most consistently associated with mobility limitations. Preliminary data regarding feasibility need to be gathered before such a tria can be effectively designed and implemented. We propose to conduct a feasibility phase that includes performing meta-analyses of existing trials and cohorts, and conducting a pilot trial to assess the effects of the interventions on several inflammatory markers and walking speed. This will allow us to refine the design, recruitment yields, target population, adherence, retention, tolerability, sample-size, and cost for the main ENRGISE trial. We will assemble the multicenter research infrastructure needed for the ENRGISE pilot and main trials, including the biorepository, and we will develop the materials needed for implementing the trials, including the protocol, manual of operations, data and safety monitoring plan, forms, quality control and quality assurance plan, and recruitment and retention materials.