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

健康，老龄化和晚年成果规划补助金（HALLO-P）是为了回应 RFA-AG-21-016。总的来说，HALLO-P附属研究人员已经领导了17项热量限制的临床试验 (CR; 3例正在进行中），入组了2，773例BMI ≥ 27 kg/m2的成人（年龄55-91岁），显示了多种有益的 与较低的疾病和残疾风险相关的生理变化。这是否会转化为实际的 疾病和残疾的减少情况尚不清楚。需要进行一项具有明确临床结局的大型多年试验 来填补证据空白时间限制喂养（TRF）可能是一个有吸引力的替代CR，如果它产生 类似的健康益处，更容易持续，并减轻了CR的肌肉和骨骼的不良损失。 这项为期3年的HALLO规划赠款的总体目标是制定一项严格的、多地点的、 一项随机临床试验（RCT），比较了随机分配至 每日CR，TRF方案，或采用创新的mHealth工具的非饮食注意力控制组， 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%）。 女性; ≥23%少数民族）提供关于可行性、干预措施实施和数据告知的关键信息 效应量测定 HALLO-P的目标是： 1.建立科学咨询委员会和其他机构，指导规划活动和设计全面的 扩大RCT的规模，让广泛的利益相关者参与，并为项目建立国家支持者。 2.完善我们的移动健康行为改变和依从性跟踪平台-HALLO-P Companion App， 优化CR和TRF干预措施的实施。 3.开展焦点小组和为期12个月的试点RCT：1）20% CR亲自交付; 2）20% CR交付 远程通过视频会议;和3）TRF（8-10小时），随意摄入热量。试点数据将有所帮助 完善招募标准，估计招募收益，并完善干预方法。我们会加倍使用- 用标记的水测量达到的CR，用连续血糖监测评估TRF的依从性。 4.使用WF OAIC储存库和HALLO-P试点对不同CR剂量的老化生物标志物变化进行建模。 现有的流行病学数据库将用于估计这些生物标志物变化的预期影响 临床结局，并推导出与入选/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下降/残疾有关;以及 5.整合新的数据、科学文献和专家建议，以制定方案，并制定知情的 同意书、操作手册、研究表格和相关系统，以允许快速启动更大的 在完成试点活动后，与该机制资助的其他U 01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.