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

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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.