Health Aging & Later-Life Outcomes Planning (HALLO-P)

健康、老龄化和晚年生活成果规划补助金(Hallo-P)是为了回应 RFA-AG-21-016。Hallo-P的附属研究人员总共领导了17项热量限制的临床试验 (CR；3正在进行)，登记2,773名成年人(年龄55-91岁)，体重指数≥为27公斤/平方米，显示出多重益处 与较低的疾病和残疾风险相关的生理变化。这是否转换为实际 疾病和残疾的减少还不清楚。需要一项具有明确临床结果的大型多年试验。 来填补这一证据空白。限时饲喂(TRF)如果能产生 类似的健康益处，更容易维持，并减轻了CR的肌肉和骨骼的不良损失。 这项为期3年的Hallo规划拨款的总体目标是为一个严格的、多地点、 随机临床试验(RCT)比较随机与临床相关的老年人的健康结果 每日CR、TRF方案或使用创新的mHealth工具的非饮食注意控制组 促进遵守。我们将完成一项为期12个月的试点研究，招募120名老年人(年龄≥60岁；50% 妇女；≥23%的少数人)提供有关可行性、干预交付和数据通知的关键信息 效果大小确定。 Hallo-P的目标是： 1.设立一个科学咨询委员会和其他结构，以指导规划活动和设计一个完整的-- 扩大有广泛利益相关者参与的区域工作队，并为该项目建立一个全国性的支持者群体。 2.改进我们的mHealth行为-更改和遵守跟踪平台-Hallo-P Companion App-以 优化CR和TRF干预措施的交付。 3.组织焦点小组和为期12个月的试点RCT：1)面对面交付20%的CR；2)交付20%的CR 远程通过视频会议；以及3)TRF(8-10小时)，可随意摄入卡路里。试点数据将有所帮助 完善招聘标准，估计招聘收益，并完善干预方法。我们将加倍使用- 标记水的测量实现了CR和连续血糖监测，以评估对TRF的依从性。 4.使用WF OAIC资料库和Hallo-P Pilot模拟不同CR剂量下老化生物标记物的变化。 现有的流行病学数据库将被用来估计这些生物标志物变化的预期影响 关于临床结果，并得出与纳入/排除标准和事件发生率相关的关键设计指标 与多种疾病、健康缺陷累积和功能衰退/残疾有关；以及 5.整合新的数据、科学文献和专家意见，以制定一项议定书，并制定知情的 同意书、操作手册、研究表和相关系统，以允许快速发射较大的 在试点活动完成后，与该机制资助的另一个U01项目协调进行试验。

The Health, Aging and Later-Life Outcomes Planning Grant (HALLO-P) is submitted in response to RFA-AG-21-016. Collectively, HALLO-P affiliated investigators have led 17 clinical trials of caloric restriction (CR; 3 ongoing), enrolling 2,773 adults (ages 55-91) with BMIs ≥ 27 kg/m2, showing multiple beneficial physiologic changes associated with lower disease and disability risk. Whether this translates to actual reductions in disease and disability is unclear. A large multi-year trial with definitive clinical outcomes is needed to fill this evidence gap. Time restricted feeding (TRF) could be an attractive alternative to CR if it produced similar health benefits, was more easily sustained, and mitigated CR’s undesirable loss of muscle and bone. The overall goal of this 3-year HALLO planning grant is to develop a protocol for a rigorous, multi-site, randomized clinical trial (RCT) comparing clinically-relevant health outcomes in older persons randomized to daily CR, a TRF regimen, or a non-dietary attention control group employing innovative mHealth tools to promote adherence. We will complete a 12-month pilot study enrolling 120 older adults (age ≥60 years; 50% women; ≥23% minority) to provide critical information on feasibility, intervention delivery, and data informing effect size determination. HALLO-P’s Objectives are to: 1. Establish a scientific advisory board and other structures to guide planning activities and the design of a full- scale RCT that engage a wide range of stakeholders and build a national constituency for the project. 2. Refine our mHealth behavior-change and adherence tracking platform—the HALLO-P Companion App—to optimize delivery of both the CR and TRF interventions. 3. Conduct focus groups and a 12-month pilot RCT of: 1) 20% CR delivered in-person; 2) 20% CR delivered remotely via video conferencing; and 3) TRF (8-10 hours) with ad libitum caloric intake. Pilot data will help refine recruitment criteria, estimate recruitment yields, and refine intervention approaches. We will use doubly- labeled water to measure achieved CR and continuous glucose monitoring to assess adherence to TRF. 4. Model aging biomarker changes for differing CR doses using WF OAIC repositories and the HALLO-P pilot. Existing epidemiological databases will be used to estimate the anticipated effect of these biomarker changes on clinical outcomes and to derive key design metrics related to inclusion/exclusion criteria, and event rates related to multi-morbidity, health deficit accumulation, and functional decline/disability; and 5. Integrate new data, the scientific literature .and expert advice to prepare a protocol, and develop informed consent forms, manuals of operation, study forms, and related systems to permit the rapid launch of the larger trial upon completion of the pilot activities in coordination with the other U01 project funded by this mechanism.