Safety monitoring in the U.S. study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (US POINTER)

Abstract

Background US POINTER is a multisite randomized clinical trial funded by the Alzheimer's Association. It is designed to evaluate whether different lifestyle interventions (exercise, nutrition, and cognitive and social stimulation) protect cognitive function over a 2‐year period in approximately 2000 older adults. Method We have designed a web‐based safety tracking system (STS) that meets the complexity of this trial that involves oversight of participants as they carry out the interventions by community partners at 5 trial sites. Result In US POINTER, participants interact with community interventionists as well as research clinic staff and clinicians. All personnel are charged with documenting potential safety events. We designed the STS to allow timely and accurate collection of safety data by study personnel regardless of their role in the study or the location of their contact with the participant. This ensures that safety data are complete. Health events entered by interventionists and clinical trial staff are reviewed by local site clinicians to determine if the event meets criteria for an adverse event (AE). If so, the clinician then determines the expectedness, relatedness, and risk of harm of the AE. These determinations are captured on the STS. Safety reporting is then reviewed and adjudicated by the central Safety Manager and the trial Safety Officer and, if needed, by the Safety Committee. The STS facilitates these processes and ensures the accuracy and consistency of safety data reporting throughout the trial. Importantly, the trial design requires that study personnel, Safety Manager, Safety Officer, and the Data Coordinating Center remain masked or unmasked as to study interventions and outcomes. The STS was designed so that access to the STS is restricted by study role in order to maintain the intervention assignment mask. These attributes of the STS help to maintain the rigor and integrity of the trial. Conclusion The innovation of the POINTER STS is that it allows for reporting of AEs obtained during any point of contact between the participant, community partners and study personnel, and allows for a multi‐level review of safety events in a centralized, efficient and timely manner thus ensuring participant’s ongoing safety throughout the trial.

The AUstralian multidomain Approach to Reduce dementia Risk by prOtecting brain health With lifestyle intervention study (AU‐ARROW): A study protocol for a single‐blind, multi‐site, randomized controlled trial

“…The nutrition intervention of AU‐ARROW is based on the MIND diet, which is a hybrid between the Mediterranean and the DASH diets that have shown beneficial effects on dementia risk 34 . The original FINGER trial 12 included a Mediterranean‐like diet (Healthy Nordic diet) and the US POINTER study 33 included the MIND diet, thus we again, aligned with US POINTER. Australia is a highly multicultural society, with more than one‐third of the population born overseas, as opposed to one in six in the United States being born overseas 35 .…”

“…The FINGER inclusion criteria were used to include those with cognitive performance at the mean level or slightly lower than expected for age according to Finnish population norms. 12 US POINTER inclusion criteria were designed to identify at-risk individuals who may benefit most from a multimodal lifestyle intervention, 33 and AU-ARROW followed their design. Diet is associated with local factors, such as the availability of ingredients, cost, and cooking habits in a region.…”

Effects of Eligibility Criteria on Patient Selection and Treatment Implications from 10 Multidomain Dementia Prevention Trials: A Population-Based Study

“…Among 1,655 screened abstracts, we identified five completed and published dementia prevention trials with at least 500 community-dwelling persons: the Dose Responses to Exercise Training (DR's EXTRA) Study published in 2010 [20], the Finnish Geriatric Intervention Neuroepidemiology 2023;57:14-24 DOI: 10.1159/000528120 Study to Prevent Cognitive Impairment and Disability (FINGER) trial in 2015 [5], the Prevention of Dementia by Intensive Vascular care (preDIVA) trial in 2016 [4], the Multidomain Alzheimer Preventive Trial (MAPT) in 2017 [2], and the Healthy Ageing Through Internet Counselling in the Elderly (HATICE) trial in 2019. From grey literature and clinical trial registries, we additionally included another five trials that are ongoing at the time of the search: the US Study to Protect Brain Health Through Lifestyle Intervention to Reduce Risk (US-POINTER), a randomized controlled trial for Multimodal Intervention to Delay Dementia and Disability in China (MIND-CHI-NA), Maintain Your Brain-Trial (MYB), AgeWell.de, and the Japan-Multimodal Intervention Trial for Prevention of Dementia (J-Mint) [21][22][23][24][25]. A flowchart leading to the included studies is presented in online supplementary eFigure1.…”

“…Half of the dementia prevention trials that were included in this study were specifically designed to recruit a sample of persons at high risk of dementia based on the presence of cardiovascular risk factors [2,5,21,23,25]. Other trials used a more pragmatic design, with few inclusion criteria and enrolment based on age cut-offs, such as DR's EXTRA and preDIVA (also see online suppl.…”

Effect of vigorous‐intensity physical activity on incident cognitive impairment in high‐risk hypertension

“…Previous studies have shown that physical activity (PA) can slow cognitive decline 7–9 . Multidomain intervention study protocols involve strategies such as blood pressure control, promotion of PA, and management of other risk factors to assess their combined impact on reducing the risk of dementia 10–12 . Yet the optimal volume and intensity of PA required for this benefit remain unclear 8 .…”