OAIC

OAIC CC Awarded Pilots (2018-Present)

Home /
OAIC-Affiliated Investigators /
Supported Pilots

FUNDED	PILOT STUDY DETAILS
2019	Hospital-induced allostatic overload: Plausible mechanism for post-hospital syndrome Primary Pepper OAIC: Mount Sinai Primary Study Team: PI: Fred Ko, MD, Assist Prof. CO-I: Albert Siu, MD, Prof. Secondary Pepper OAIC:Boston, UCLA, Johns Hopkins Secondary Study Team: Boston: Drs. Levine & Latham UCLA: Drs. Goldwater & Seeman JHU: Drs. Walston and Leff The purpose of this Pepper Coordinating Center pilot study is to investigate multisystem physiologic dysfunction (allostatic load or AL) associated with the hospital-environment in older adults who undergo traditional hospitalization for acute illnesses versus those who receive care through Hospitalization at Home (HaH) program. This collaborative pilot study is implemented by leveraging the unique resources and expertise of the Mount Sinai (Drs. Ko and Siu; HaH), Boston (Drs. Levine and Latham; HaH), UCLA (Drs. Goldwater and Seeman; PHS, allostasis) and Johns Hopkins (Drs. Walston and Leff; biomarker, hospital-induced stress) Pepper Centers. Aim 1 of this study will help to determine feasibility of this line of research while generating preliminary data to better quantify stress exposures associated with traditional hospitalization. Aim 2 will explore biomarkers and measures of AL that may help to inform the development of a novel measure of hospitalization-associated AL. The completion of this pilot will provide crucial preliminary data to inform the feasibility of an adequately powered, multisite study to further this line of research.
2020	Expanding the capacity for OAIC digital phenotyping using Realtime, Online Assessment and Mobility Monitoring (ROAMM) of falls in older adults Primary Pepper OAIC: UFL Primary Study Team: PI: Todd Manini, Cpo-I: Mamoun Al Mardini Secondary Pepper OAIC:Yale University Secondary Study Team: Tom Gill Our development of the Real-time Online Assessment and Mobility Monitor (ROAMM) platform at the UF OAIC offers long-term and continuous connectivity, bidirectional interactivity and remote programmability through a smartwatch. ROAMM includes: 1) a secure smart watch app which collects and summarizes sensor-monitored data (e.g. tri-axial accelerometer, GPS location); 2) a graphical interface allowing ecological momentary assessments; 3) interface and/or voice recording for cognitive assessment; and 4) secure servers for configuring the application parameters, data storage, advanced analytics, web-based data visualization and remote management of sensors. From these features, we obtain activity/mobility patterns, ecological momentary assessment of complex symptoms (pain, fatigue, mood), patient reported outcomes (disability), reported health events and cognitive performance (our domains of interest). We aim to leverage our efforts on ROAMM, experiences from STRIDE and what is learned in this pilot study to initiate an inter-OAIC electronic-cohort. In this type of cohort, participants are monitored remotely using smart devices that sync passive sensors with conveniently delivered questions about health and performance tests on the smartwatch. This approach removes in-person repeated follow-up visits yet gains detailed objective information surrounding the onset and recovery from a fall or other episodic health events (e.g. hospitalizations). This pilot project aims to implement ROAMM at the Yale OAIC where we will enroll 25 older men and women, 70+ years of age to ensure we are capable of successfully transferring the technology and collecting data at another OAIC site. Specifically, we will develop and evaluate the following critical elements to scale the system for assembling an inter-OAIC electronic-cohort: eligibility criteria, quality assurance plans, webinar training materials, data security, helpdesk ticket system, web portal refinement, data visualizations, inter-site participant compliance, shared mobile data repository, and staff and participant usability. When completed, we will be positioned to compete in the recently released National Advisory Council on Aging approved concept on "Artificial Intelligence and Technology Centers for Aging Research". Our vision is to create not only a single ROAMM resource, but also a foundation for creating a virtual technology network connected between OAICs. These activities will ensure research on older adults is keeping pace with the state- of-the-art "smart and connected" health with mobile technology.
2021	Assessing geroscience outcomes in older adults randomized to senolytic therapy Primary Pepper OAIC: WFU Primary Study Team: PI: Miranda Orr Secondary Pepper OAIC:University of Texas Health Sciences San Antonio Secondary Study Team: Mitzi Gonzales, PhD Nicolas Musi, MD Sara Espinoza, MD Mini Jacob, PhD Habil Zare, PhD Mohamad Habes, PhD Preclinical data indicate that cellular senescence contributes to the underlying functional decline across organ systems in aging animals. Therefore we hypothesize that therapeutically clearing senescent cells with senolytics (dasatinib with quercetin (D+Q)) could improve the biological aging process and would be evidenced by improved health outcomes. We have been awarded extramural funding to conduct a multisite Phase 2 clinical trial to test the safety and efficacy of D+Q in older adults with mild cognitive impairment/early Alzheimer's disease. Our parent study focuses exclusively on Alzheimer's disease specific outcomes of dementia, brain imaging and cerebrospinal fluid biomarkers. As this novel therapeutic approach enters clinical trials, we aim to address a fundamental limitation of biomedical research and health-care delivery: the practice of studying and treating individual diseases and co-morbid health conditions in isolation. Therefore this ancillary study represents an opportunity to leverage our clinical trial to include outcome measures relevant to aging adults and study them in synchrony. Specifically in Aim I we will evaluate physical function, frailty and frailty-related characteristics, and their response to senolytic therapy. Aim II will measure DNA methylation to determine epigenetic age. These data will inform whether senolytic therapy modulates epigenetic age, and how epigenetic age correlates with physical function and frailty in older adults with dementia. In Aim III we will utilize a newly developed, innovative machine-learning algorithm that will inform whether senescent cell clearance can impact biological brain aging and/or Alzheimer's disease processes. We will correlate these indices to physical function, frailty and DNA methylation measures, as well as change in cellular senescence levels. To ensure the successful completion of these study aims we have assembled a team of investigators from Wake Forest and San Antonio OAICs with experience ranging from early career (RL5 scholars) to well established clinicians/scientists for oversight and guidance. The team's expertise spans basic biology of aging, geroscience, clinical trials, Alzheimer's disease, bioinformatics and statistics. Ultimately, this study will provide critical insights on the impact of cellular senescence on functional outcomes in older adults and evaluate the feasibility of adding age- relevant outcomes to an Alzheimer's disease focused trial. Moreover, the harmonized cross-OAIC protocols will provide a foundation for future geroscience interventional studies.
2021	Establishing a humanized microbiota-associated mouse colony to study aging Primary Pepper OAIC: UTHSCSA Primary Study Team: PI: Kelly Reveles Co-I: Nicholas Musi Secondary Pepper OAIC:University of Michigan Secondary Study Team: Raymond Yung Vincent Young Due to the complexity of the gut microbiome, few studies have been able to demonstrate causal relationships in humans. Fecal microbiota transplantation of human fecal samples to germ-free mice creates a powerful system to study the structure and function of microbial communities in vivo. This humanized microbiota-associated (HMA) mouse model is considered the gold standard to establish causal relationships between human phenotypes and altered gut microbiota. The HMA model provides a unique opportunity to demonstrate causal relationships in humans about mechanistic pathways and how they impact microbiome dysbiosis, clinical disease states, and aging; nonetheless, the causal impact of the microbiome on healthspan and lifespan has not been previously investigated. To address this gap, we propose the following Aims: Aim 1 will establish a colony of HMA mice to provide a foundation for a national resource for Geroscience-oriented research on the microbiome; Aim 2 will evaluate the impact of aging-related microbiome disruptions on short-term healthspan outcomes. We hypothesize that older, frailty-associated human microbiota will be associated with poorer healthspan outcomes. To accomplish these aims, San Antonio investigators will conduct a cross-sectional study of 1) young, healthy adults, 2) older, healthy adults, and 3) older, frail adults. Stool samples from humans will be transplanted via oral gavage to germ-free mice housed at the University of Michigan germ-free mouse facility. Study outcomes will include: 1) success of microbial engraftment in mice in each group; and 2) aging-related healthspan outcomes between groups in the human cohorts and humanized mice cohorts. This multicenter, multidisciplinary (translational and clinical scientists) collaboration will capitalize on human clinical study expertise at the San Antonio OAIC and microbiome-associated healthspan expertise and germ-free mouse facilities at the University of Michigan OAIC. The proposed research is expected to serve as a model for future healthspan and lifespan studies and informing new therapeutic targets to promote healthy aging. Further, the HMA model will be used to progress to a larger, definitive trial and will serve as a resource for additional collaboration within the OAIC network.
2021	Modifying brain activity and behavior to improve life-space mobility and physical activity in older adults Primary Pepper OAIC: Boston Primary Study Team: PI: Brad Manor, PhD Co-I: Amy Lo, PhD; Lewis Lipsitz, MD Secondary Pepper OAIC:University of Pittsburgh Secondary Study Team: Andrea Rosso, PhD We proposed to conduct a pilot randomized controlled trial (RCT) to test the effects of a behavioral intervention to increase physical activity combined with a 10-session tDCS intervention targeting the left dlPFC. Trial endpoints will focus on the quantity and quality of daily physical activity as measured by 1) Fitbit (i.e., step counts), and 2) GPS tracking of the magnitude and stability of participant life space and the timing of daily mobility. We will also work to implement an OAIC-recommended functional assessment at baseline and at multiple post-intervention follow-ups. The target population will be underserved, physically-inactive older adults without major overt illness or disease, who live within subsidized urban senior housing facilities. This study is expected to stimulate future grant activity by providing proof-of-concept that tDCS may be used to augment a behavioral intervention to increase goal-directed physical activity and daily life-space mobility in older adults with limited access to healthcare-related resources. This study has completed data collection from one subsidized housing site within the Greater Boston area. The last participant was enrolled on 6/21/2022. The last final assessment was completed on 7/28/2022. The last data information (i.e. Fitbit) was collected on 11/3/2022. In total, we enrolled 18 older adults (with a target of 16): 15 participants completed the study and three withdrew due to medical issue or family emergency. All 18 enrolled participants agreed to be tracked with their GPS when they signed up. However, in addition to three withdrawals, one refused and three forgot to use the GPS after the intervention, leading a total of 11 participants having the post-intervention GPS information. We have initiated preliminary data analysis, are currently analyzing the data and preparing for manuscript and future grant submission.
2021	The Health Effects of Prolonged Social Isolation, Loneliness During the COVID-19 Pandemic Primary Pepper OAIC: UCSF Primary Study Team: PI: Ashwin Kotwal, MD, MS Secondary Pepper OAIC:Northwestern University Secondary Study Team: Co-I: Rachel O'Conor We will leverage an active NIA cohort study of older adults with =1 chronic conditions to expand investigations on COVID-19’s impact on psychosocial health, functional needs, and health behaviors. The C3 study remains active with an NIA COVID-19 supplement; data collection will continue through 2025. The cohort was derived from 5 active studies with uniform data collection on a range of functional status outcomes prior to COVID-19 and with continued electronic health records access. C3 participants are diverse by socioeconomic status, race, ethnicity, gender, health literacy, and comorbidity. At the time of submission, a total of 5 survey waves had been conducted (the first assessment was conducted in the first week of the outbreak, March 13- 20, 2020; 83-94% retention to date), and three additional waves were planned for 2021. With this project, we merge mutual interests in a collaborative partnership between UCSF and Northwestern Pepper Centers to characterize the psychological, social, and physical health and healthcare experiences of diverse older adults contending with =1 chronic conditions throughout the course of the pandemic. Specifically, new measures of social isolation, loneliness, and functional support needs will be added to upcoming C3 survey waves. We completed Aim 1 describing trajectories of persistent loneliness during the pandemic and published the manuscript in Journal of American Geriatrics Society (see reference below). This paper was well-received, with results presented at multiple conferences, most notably at the 2022 American Public Health Association (oral presentation) and 2022 American Geriatrics Society (Presidential Poster Session). We are in the process of conducting analysis for Aim 2 of the study focused on understanding if persistent loneliness, social isolation, and tangible support are associated with declines in physical function and mental health. We found signals that this may be the case (non-significant relationships), and are awaiting ongoing data collection through the parent R01 study to further flesh out this potential finding.
2022	Heterogeneity of Human Adipose Tissue Senescence and its Relationship to Physical Function and Mobility Primary Pepper OAIC: UConn Primary Study Team: PI: Ming Xu, PhD Secondary Pepper OAIC:Wake Forest University School of Medicine Secondary Study Team: Jamie Justice, PhD Although progressive decline in mobility with aging has been partially attributed to loss of skeletal muscle mass and function, adipose tissue (AT) is also likely to significantly influence mobility. Cell senescence is triggered by molecular damage and metabolic stressors that result in cell cycle arrest and a senescent phenotype of altered gene expression and pro-inflammatory secretome. Senescent cells accumulate with aging in many tissues, including AT. Preliminary studies by the team demonstrates that senescent cells in AT play a causal role in physical dysfunction in mice, and one senescence biomarker, p16INK4a, in fat is associated with poorer physical function in older women. However, a more comprehensive investigation is highly desired on cellular and molecular changes in human AT with physical dysfunction. Here, we will obtain 10 AT samples per group from participants with slow (< 1.0 m/s) and fast walking speed (=1.2 m/s). We will perform single nucleus transcriptomics (SNT) on these tissues and acquire transcriptomics at single-cell resolution. By comparing between fast and slow groups, we propose to identify cells type alteration, molecular changes within each cell type, and the association between senescence markers and walking speed. Results from this work will likely reveal a number of novel mechanisms and therapeutic targets in AT responsible for physical function decline with aging.
2022	In-clinic and real-world gait quality in visually impaired older adults with glaucoma Primary Pepper OAIC: Michigan Primary Study Team: PI: Amanda Bickett, PhD Secondary Pepper OAIC:University of Pittsburgh Secondary Study Team: Rakie Cham, PhD The long-term goal of this line of research is to develop in-clinic gait metrics that provide ecologically valid assessments of physical function in the real world, for use in both clinical patient care and trial design. The primary goal of the proposed pilot is to test the feasibility of determining relationships between wearable Inertial Measurement Unit (IMU)-acquired gait quality measurements acquired in clinic and in the real world in older adults (aged = 70) with varying levels of glaucomatous visual field loss (n=45). It incorporates two specific aims: (1) Assessment of the validity of an inclinic 2-minute walk test (2MWT-C) for capturing real-world performance, as measured with both an at-home 2-minute walk test (2MWT-H) and a 3-day free-walking trial; (2) Examination of the association of gait quality metrics with self-reported vision-related activity limitation, measured using the Glaucoma Activity Limitation (GAL-9) questionnaire. In MPI Bicket’s pilot work, patients with glaucoma prioritized maintaining independence over avoiding downsides of glaucoma treatment, which include discomfort, inconvenience, and cost. By clarifying ways we can measure glaucoma-associated gait changes and their functional impact, this project aligns with the Pepper Centers’ goal of “increase[ing] scientific knowledge leading to better ways to maintain… independence in older persons.” This proposed joint study brings together two strong programs - the Universities of Pittsburgh and Michigan - with expertise in aging and gait biomechanics (Cham and Redfern from Pittsburgh, Alexander and Ojeda from Michigan) and expertise in the impact of visual impairment on mobility (Bicket from Michigan and Cham from Pittsburgh). We also include two early-stage investigators, one from ophthalmology who specializes in glaucoma (Bicket), and one from physical therapy specializing in mobility and clinical gait assessments (Baillargeon from Pittsburgh). The team has experience in measurement of gait quality and vision-related functional impairment in older adults with glaucoma (Bicket, Cham) and in using IMUs to study in-clinic and real-world gait quality (Redfern, Baillargeon) and losses of balance (Alexander, Ojeda). Data from this pilot study will provide a foundation for future studies analyzing links between vision impairment, self-reported function, and gait quality in older adults, and will support future career development awards (Bicket, Baillargeon), studies of functional recovery after glaucoma surgery (Bicket, Alexander), and studies examining central processing changes in the brain in glaucoma (Cham, Redfern).
2023	Home time and health expenditures after treat-and-release ED visits Primary Pepper OAIC: Yale Primary Study Team: PI: Cameron Gettel Secondary Pepper OAIC:Duke University Secondary Study Team: Nicky Hastings Persons aged 65 years and older account for over 22 million emergency department (ED) visits annually, with approximately 65% of older adult ED patients being discharged home (i.e. ‘treat-and-release’ ED visits). Particularly during the time period after seeking emergency care metrics of success are often limited to repeat healthcare utilization. In the transition towards addressing patient-centered outcomes, home time, defined as days alive and out of acute and post-acute institutional care settings, is an outcome measure that has recently gained momentum. Furthermore, older adults discharged home from the ED are at risk for increased health care expenditures. To date, no specific evaluations have assessed home time or healthcare expenditures after treat-and-release ED visits nor their subsequent trajectories stratified by functional status, despite the growing interest in using home time as a quality-of-life measure. Our long-term goal is to study and improve ED care transitions using patient-centered outcomes, specifically targeting at-risk older adult populations seeking emergency care. The overall objective of this proposal is to produce foundational data regarding home time and healthcare expenditures, and we hypothesize that particularly at-risk populations, including the oldest old (> 85 years of age), racial and ethnic minorities, and those with Alzheimer’s Disease or Related Dementias (ADRD), will have reduced home time and increased healthcare expenditures relative to their peers in the time period following a treat-and-release ED visit. The rationale for this project is that a greater understanding of home time and healthcare expenditures after treat-and release ED visits will provide critical data regarding the consideration of using home time as a patient-centered measure after seeking emergency care and inform intervention development targeting those at-risk of negative outcomes. We will achieve this objective with the following two aims: 1) Examine demographic and clinical characteristics associated with reduced home time and increased healthcare expenditures in the 7-, 30-, 90-, and 180-days following a treat-and-release ED visit; and 2) Estimate the effect of treat-and-release ED visits on subsequent home time and healthcare expenditures in a propensity-matched sample. We will perform a secondary data analysis using the 1999-2019 Medicare Current Beneficiary Survey (MCBS) and stratify populations within the Aims by the Activity Limitation Stages defining physical function capabilities, isolating the critical role that functional status plays in outcomes after treat-and release ED visits. We anticipate using adjusted Poisson regression modeling and a generalized linear model with log-link and ? distribution to respectively identify the association between key independent variable groups of interest and home time count as well as healthcare expenditures following a treat-and-release ED visit. We also anticipate estimating propensity score models to determine the effect of treat-and-release ED visits relative to those without treat-and-release ED visits with regards to home time and healthcare expenditures.
2024	Inhibition of ceramide synthesis: a viable strategy to reverse metabolic determinants of sarcopenic obesity? Primary Pepper OAIC: UTHSCSA Primary Study Team: PI: Juan Pablo Palavacini Secondary Pepper OAIC:University of Texas Medical Branch Secondary Study Team: Co-I: Andrew Murton Older adults who survive critical illness are at risk for increased disability and symptom burden, potentially compromising their independence and quality of life. Existing interventions following critical illness have failed to mitigate ensuing disability. Reduced physical activity, a known risk factor for disability among older adults, and an effective treatment strategy to improve function following other acute stressors such as congestive heart failure, has not been targeted in interventions to improve outcomes following critical illness. Studies objectively describing physical activity following critical illness are limited by inclusion of relatively few older adults, collection of information at widely spaced intervals and for a short duration following hospitalization, and failure to evaluate underlying barriers and its relationship with functional outcomes. There is an urgent need to characterize physical activity immediately following critical illness, understand its relationship with downstream functional outcomes, and identify modifiable facilitators and barriers of activity among older survivors of critical illness. Without this knowledge, crucial information that could inform the development of targeted interventions to enhance physical activity and improve functional outcomes among older adults following a critical illness may be lost. Our preliminary research has found that the prevalence of symptoms associated with restricted activity increases 5-fold in the month following critical illness (manuscript under revision), and that these restricting symptoms are associated with increased disability. However, this work was limited by the use of recall-based assessments that may not accurately reflect how symptoms affect physical activity in real time. The overall objective of this proposal is to elucidate the relationship between post-hospitalization physical activity and downstream functional outcomes and identify whether symptoms of physical and mental health are barriers to being active after critical illness. Our central hypothesis is that physical activity immediately following hospitalization critical illness will be associated with downstream function and will be reduced in the presence of concurrent symptoms of physical and mental health. To test this hypothesis, we will use high quality data derived from a novel smartwatch-based platform, Real-time Online Activity and Mobility Monitor (ROAMM), that has been validated among community-dwelling older adults. This platform will enable remote and real-time tracking of symptoms and patient-reported outcomes via ecological momentary assessments (EMAs), accelerometer-derived physical activity, and objective measures of function.
2024	Remote Monitoring of Symptoms, Activity, Disability, and Life-Space Mobility Among Older ICU Survivors: a Pilot Study Primary Pepper OAIC: Yale Primary Study Team: PI: Snigdha Jain Co-I: Lauren Ferrante, Tom Gill Secondary Pepper OAIC:University of Florida Secondary Study Team: Co-I: Mamoun Al Mardini, Todd Manini Older adults who survive critical illness are at risk for increased disability and symptom burden, potentially compromising their independence and quality of life. Existing interventions following critical illness have failed to mitigate ensuing disability. Reduced physical activity, a known risk factor for disability among older adults, and an effective treatment strategy to improve function following other acute stressors such as congestive heart failure, has not been targeted in interventions to improve outcomes following critical illness. Studies objectively describing physical activity following critical illness are limited by inclusion of relatively few older adults, collection of information at widely spaced intervals and for a short duration following hospitalization, and failure to evaluate underlying barriers and its relationship with functional outcomes. There is an urgent need to characterize physical activity immediately following critical illness, understand its relationship with downstream functional outcomes, and identify modifiable facilitators and barriers of activity among older survivors of critical illness. Without this knowledge, crucial information that could inform the development of targeted interventions to enhance physical activity and improve functional outcomes among older adults following a critical illness may be lost. Our preliminary research has found that the prevalence of symptoms associated with restricted activity increases 5-fold in the month following critical illness (manuscript under revision), and that these restricting symptoms are associated with increased disability. However, this work was limited by the use of recall-based assessments that may not accurately reflect how symptoms affect physical activity in real time. The overall objective of this proposal is to elucidate the relationship between post-hospitalization physical activity and downstream functional outcomes and identify whether symptoms of physical and mental health are barriers to being active after critical illness. Our central hypothesis is that physical activity immediately following hospitalization critical illness will be associated with downstream function and will be reduced in the presence of concurrent symptoms of physical and mental health. To test this hypothesis, we will use high quality data derived from a novel smartwatch-based platform, Real-time Online Activity and Mobility Monitor (ROAMM), that has been validated among community-dwelling older adults. This platform will enable remote and real-time tracking of symptoms and patient-reported outcomes via ecological momentary assessments (EMAs), accelerometer-derived physical activity, and objective measures of function.