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Background: Studies of the relationship between vitamin D and physical functioning have had inconsistent results., Methods: Physical functioning measures were collected for up to 2 years during a 2-stage, Bayesian, response-adaptive, randomized trial of 4 doses of vitamin D3 supplementation (200 [control], 1 000, 2 000, and 4 000 IU/day) to prevent falls. Two community-based research units enrolled adults aged ≥70 years, with elevated fall risk and serum 25-hydroxyvitamin D level of 10-29 ng/mL. The Pooled Higher Doses (PHD) group (≥1 000 IU/day, n = 349) was compared to the control group (n = 339) on changes in Short Physical Performance Battery (SPPB) score and its component tests, Timed Up-and-Go (TUG) test, 6-minute walk distance, and grip strength., Results: The trial enrolled 688 participants. Mean age was 77.2 years, 56.4% were male, 79.7% White, and 18.2% Black. While the PHD and control groups both lost function over time on most outcomes, the 2 groups did not show differential change overall on any outcome. Incidence of transitioning to poor functioning on gait speed, SPPB score, or TUG test did not differ by dose group., Conclusion: In older persons with low serum 25-hydroxyvitamin D level and elevated fall risk, high-dose vitamin D supplementation, ≥1 000 IU/day, did not improve measures of physical function compared to 200 IU/day., Clinical Trial Registration: NCT02166333., (© The Author(s) 2021. Published by Oxford University Press on behalf of The Gerontological Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Introduction: Online tools are increasingly utilized in clinical trial recruitment. A/B testing is an effective technology used in political campaigns and commercial marketing to improve contributions or sales. However, to our knowledge, A/B has not been described in the context of clinical trial recruitment., Methods: Two A/B testing experiments were implemented on the recruitment website of the Study To Understand Fall Reduction and Vitamin D in You (STURDY), a response-adaptive, two-stage, randomized controlled trial. Commercial A/B platforms randomized web-users to different versions of the trial's website landing page; Experiment 1 included two infographic versions and Experiment 2 included three video versions. We compared web-user engagement metrics between each version and the original landing page. We determined the effect of each version compared to the original landing page on the likelihood of a web-user to (1) request more information about the trial, (2) complete a screening visit, or (3) enroll in the trial., Results: A total of 2605 and 374 web-users visited the trial's website during Experiment 1 and 2, respectively. Response to the online interest form significantly differed by infographic version in Experiment 1. The number of individuals who engaged with website content and pages significantly differed by video in Experiment 2., Conclusion: In a pilot study implementing A/B testing of a clinical trial recruitment website, different versions of the website led to differences in web-user engagement and interest in the trial. A/B testing tools offer a promising approach to test the effectiveness of clinical trial recruitment materials and to optimize recruitment campaigns., Clinical Trial Registration: This trial is registered at ClinicalTrials.gov. The trial registration number is NCT02166333. The URL is: https://clinicaltrials.gov/ct2/show/NCT02166333 Trial Registration Number: NCT02166333 Trial Register: ClinicalTrials.gov., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Background/objectives: To assess whether vitamin D supplementation prevents specific fall subtypes and sequelae (e.g., fracture)., Design: Secondary analyses of STURDY (Study to Understand Fall Reduction and Vitamin D in You)-a response-adaptive, randomized clinical trial., Setting: Two community-based research units., Participants: Six hundred and eighty-eight participants ≥70 years old with elevated fall risk and baseline serum 25-hydroxyvitamin D levels of 10-29 ng/ml., Intervention: 200 IU/day (control), 1000 IU/day, 2000 IU/day, or 4000 IU/day of vitamin D3., Measurements: Outcomes included repeat falls and falls that were consequential, were injurious, resulted in emergency care, resulted in fracture, and occurred either indoors or outdoors., Results: After adjustment for multiple comparisons, the risk of fall-related fracture was greater in the pooled higher doses (≥1000 IU/day) group compared with the control (hazard ratio [HR] = 2.66; 95% confidence interval [CI]:1.18-6.00). Although not statistically significant after multiple comparisons adjustment, time to first outdoor fall appeared to differ between the four dose groups (unadjusted p for overall difference = 0.013; adjusted p = 0.222), with risk of a first-time outdoor fall 39% lower in the 1000 IU/day group (HR = 0.61; 95% CI: 0.38-0.97; unadjusted p = 0.036; adjusted p = 0.222) and 40% lower in the 2000 IU/day group (HR = 0.60; 95%CI 0.38-0.97; p = 0.037; adjusted p = 0.222), each versus control., Conclusion: Vitamin D supplementation doses ≥1000 IU/day might have differential effects on fall risk based on fall location and fracture risk, with the most robust finding that vitamin D doses between 1000 and 4000 IU/day might increase the risk of first time falls with fractures. Replication is warranted, given the possibility of type 1 error., (© 2021 The Authors. Journal of the American Geriatrics Society published by Wiley Periodicals LLC on behalf of The American Geriatrics Society.)

Background: Vitamin D supplementation may prevent falls in older persons, but evidence is inconsistent, possibly because of dosage differences., Objective: To compare the effects of 4 doses of vitamin D 3 supplements on falls., Design: 2-stage Bayesian, response-adaptive, randomized trial. (ClinicalTrials.gov: NCT02166333)., Setting: 2 community-based research units., Participants: 688 participants, aged 70 years and older, with elevated fall risk and a serum 25-hydroxyvitamin D [25-(OH)D] level of 25 to 72.5 nmol/L., Intervention: 200 (control), 1000, 2000, or 4000 IU of vitamin D 3 per day. During the dose-finding stage, participants were randomly assigned to 1 of the 4 vitamin D 3 doses, and the best noncontrol dose for preventing falls was determined. After dose finding, participants previously assigned to receive noncontrol doses received the best dose, and new enrollees were randomly assigned to receive 200 IU/d or the best dose., Measurements: Time to first fall or death over 2 years (primary outcome)., Results: During the dose-finding stage, the primary outcome rates were higher for the 2000- and 4000-IU/d doses than for the 1000-IU/d dose, which was selected as the best dose (posterior probability of being best, 0.90). In the confirmatory stage, event rates were not significantly different between participants with experience receiving the best dose (events and observation time limited to the period they were receiving 1000 IU/d; n  = 308) and those randomly assigned to receive 200 IU/d ( n  = 339) (hazard ratio [HR], 0.94 [95% CI, 0.76 to 1.15]; P  = 0.54). Analysis of falls with adverse outcomes suggested greater risk in the experience-with-best-dose group versus the 200-IU/d group (serious fall: HR, 1.87 [CI, 1.03 to 3.41]; fall with hospitalization: HR, 2.48 [CI, 1.13 to 5.46])., Limitations: The control group received 200 IU of vitamin D 3 per day, not a placebo. Dose finding ended before the prespecified thresholds for dose suspension and dose selection were reached., Conclusion: In older persons with elevated fall risk and low serum 25-(OH)D levels, vitamin D 3 supplementation at doses of 1000 IU/d or higher did not prevent falls compared with 200 IU/d. Several analyses raised safety concerns about vitamin D 3 doses of 1000 IU/d or higher., Primary Funding Source: National Institute on Aging.

Background: To assess whether vitamin D3 supplementation attenuates the decline in daily physical activity in low‐functioning adults at risk for falls. Methods: Secondary data analyses of STURDY (Study to Understand Fall Reduction and Vitamin D in You), a response‐adaptive randomized clinical trial. Participants included 571 adults aged 70 years and older with baseline serum 25(OH)D levels of 10–29 ng/mL and elevated fall risk, who wore a wrist accelerometer at baseline and at least one follow‐up visit and were randomized to receive: 200 IU/day (control), 1000, 2000, or 4000 IU/day of vitamin D3. Objective physical activity quantities and patterns (total daily activity counts, active minutes/day, and activity fragmentation) were measured for 7‐days, 24‐h/day, in the free‐living environment using the Actigraph GT9x over up to 24‐months of follow‐up. Results: In adjusted models, physical activity quantities declined (p < 0.001) and became more fragmented, or "broken up", (p = 0.017) over time. Supplementation with vitamin D3 did not attenuate this decline. Changes in physical activity were more rapid among those with baseline serum 25(OH)D <20 ng/mL compared to those with baseline 25(OH)D levels of 20–29 ng/mL (time*baseline 25(OH)D, p < 0.05). Conclusion: In low‐functioning older adults with serum 25(OH)D levels 10–29 ng/mL, vitamin D3 supplementation of 1000 IU/day or higher did not attenuate declines in physical activity compared with 200 IU/day. Those with baseline 25(OH)D <20 ng/mL showed accelerated declines in physical activity. Alternative interventions to supplementation are needed to curb declines in physical activity in older adults with low serum 25(OH)D. [ABSTRACT FROM AUTHOR]

Background Wearable devices have become widespread in research applications, yet evidence on whether they are superior to structured clinic-based assessments is sparse. In this manuscript, we compare traditional, laboratory-based metrics of mobility with a novel accelerometry-based measure of free-living gait cadence for predicting fall rates. Methods Using negative binomial regression, we compared traditional in-clinic measures of mobility (6-minute gait cadence, speed, and distance, and 4-m gait speed) with free-living gait cadence from wearable accelerometers in predicting fall rates. Accelerometry data were collected with wrist-worn Actigraphs (GT9X) over 7 days in 432 community-dwelling older adults (aged 77.29 ± 5.46 years, 59.1% men, 80.2% White) participating in the Study to Understand Fall Reduction and Vitamin D in You. Falls were ascertained using monthly calendars, quarterly contacts, and ad hoc telephone reports. Accelerometry-based free-living gait cadence was estimated with the Adaptive Empirical Pattern Transformation algorithm. Results Across all participants, free-living cadence was significantly related to fall rates; every 10 steps per minute higher cadence was associated with a 13.2% lower fall rate (p  = .036). Clinic-based measures of mobility were not related to falls (p >.05). Among higher-functioning participants (cadence ≥100 steps/minute), every 10 steps per minute higher free-living cadence was associated with a 27.7% lower fall rate (p  = .01). In participants with slow baseline gait (gait speed <0.8 m/s), all metrics were significantly associated with fall rates. Conclusion Data collected from biosensors in the free-living environment may provide a more sensitive indicator of fall risk than in-clinic tests, especially among higher-functioning older adults who may be more responsive to intervention. Clinical Trial Registration NCT02166333 [ABSTRACT FROM AUTHOR]

Context The Study to Understand Fall Reduction and Vitamin D in You (STURDY), a randomized trial enrolling older adults with low 25-hydroxyvitamin D [25(OH)D], demonstrated vitamin D supplementation ≥ 1000 IU/day did not prevent falls compared with 200 IU/day, with doses ≥ 2000 IU/day potentially showing safety concerns. Objective To examine associations of achieved and change in 25(OH)D concentrations after 3 months of vitamin D supplementation with fall risk. Design Observational analysis of trial data. Setting General community. Participants A total of 637 adults aged ≥ 70 with baseline 25(OH)D concentrations 10 to 29 ng/mL and elevated fall risk. Three-month on-treatment absolute 25(OH)D; absolute and relative changes from baseline. Main Outcome Measures Incident first fall (primary) and first consequential fall (injury or sought medical care) up to 24 months. Cox models were adjusted for sociodemographics, season, Short Physical Performance Battery, and body mass index. Results At baseline, mean (SD) age was 77.1 (5.4) years and 25(OH)D was 22.1 (5.1) ng/mL; 43.0% were women and 21.5% non-White. A total of 395 participants experienced ≥ 1 fall; 294 experienced ≥ 1 consequential fall. There was no association between absolute achieved 25(OH)D and incident first fall (30-39 vs < 30 ng/mL hazard ratio [HR], 0.93; 95% CI, 0.74-1.16; ≥40 vs < 30 ng/mL HR, 1.09; 95% CI, 0.82-1.46; adjusted overall P  = 0.67), nor absolute or relative change in 25(OH)D. For incident consequential first fall, the HR (95% CI) comparing absolute 25(OH)D ≥ 40 vs < 30 ng/mL was 1.38 (0.99-1.90). Conclusion Achieved 25(OH)D concentration after supplementation was not associated with reduction in falls. Risk of consequential falls may be increased with achieved concentrations ≥ 40 ng/mL. Trial Registration ClinicalTrials.gov: NCT02166333 [ABSTRACT FROM AUTHOR]

Background: Low serum 25-hydroxyvitamin D [25(OH)D] level is associated with a greater risk of frailty, but the effects of daily vitamin D supplementation on frailty are uncertain. This secondary analysis aimed to examine the effects of vitamin D supplementation on frailty using data from the Study To Understand Fall Reduction and Vitamin D in You (STURDY).Methods: The STURDY trial, a two-stage Bayesian, response-adaptive, randomized controlled trial, enrolled 688 community-dwelling adults aged ≥ 70 years with a low serum 25(OH)D level (10-29 ng/mL) and elevated fall risk. Participants were initially randomized to 200 IU/d (control dose; n = 339) or a higher dose (1000 IU/d, 2000 IU/d, or 4000 IU/d; n = 349) of vitamin D3. Once the 1000 IU/d was selected as the best higher dose, other higher dose groups were reassigned to the 1000 IU/d group and new enrollees were randomized 1:1 to 1000 IU/d or control group. Data were collected at baseline, 3, 12, and 24 months. Frailty phenotype was based on number of the following conditions: unintentional weight loss, exhaustion, slowness, low activity, and weakness (≥ 3 conditions as frail, 1 or 2 as pre-frail, and 0 as robust). Cox proportional hazard models estimated the risk of developing frailty, or improving or worsening frailty status at follow-up. All models were adjusted for demographics, health conditions, and further stratified by baseline serum 25(OH)D level (insufficiency (20-29 ng/mL) vs. deficiency (10-19 ng/mL)).Results: Among 687 participants (mean age 77.1 ± 5.4, 44% women) with frailty assessment at baseline, 208 (30%) were robust, 402 (59%) were pre-frail, and 77 (11%) were frail. Overall, there was no significant difference in risk of frailty outcomes comparing the pooled higher doses (PHD; ≥ 1000 IU/d) vs. 200 IU/d. When comparing each higher dose vs. 200 IU/d, the 2000 IU/d group had nearly double the risk of worsening frailty status (HR = 1.89, 95% CI: 1.13-3.16), while the 4000 IU/d group had a lower risk of developing frailty (HR = 0.22, 95% CI: 0.05-0.97). There were no significant associations between vitamin D doses and frailty status in the analyses stratified by baseline serum 25(OH)D level.Conclusions: High dose vitamin D supplementation did not prevent frailty. Significant subgroup findings might be the results of type 1 error.Trial Registration: ClinicalTrials.gov: NCT02166333 . [ABSTRACT FROM AUTHOR]

Background Vitamin D3 supplementation is considered a potential intervention to prevent orthostatic hypotension (OH) based on observational evidence that vitamin D levels are inversely associated with OH. With data from The Study to Understand Fall Reduction and Vitamin D in You (STURDY), a double-blind, randomized, response-adaptive trial, we determined if higher doses of vitamin D3 reduced risk of OH. Methods STURDY tested the effects of higher (1,000+ IU/day, i.e. 1,000, 2,000, and 4,000 IU/day combined) vs. lower-dose vitamin D3 (200 IU/day, comparison) on fall risk in adults ages 70 years and older with low serum 25-hydroxyvitamin D (25(OH)D, 10–29 ng/ml). OH was determined at baseline, 3, 12, and 24 months by taking the difference between seated and standing blood pressure (BP). OH was defined as a drop in systolic or diastolic BP of at least 20 or 10 mm Hg after 1 minute of standing. Participants were also asked about OH symptoms during the assessment and the preceding month. Results Among 688 participants (mean age 77 [SD, 5] years; 44% women; 18% Black), the mean baseline systolic/diastolic BP was 130 (19)/67 (11) mm Hg, serum 25(OH)D was 22.1 (5.1) ng/ml, and 2.8% had OH. There were 2,136 OH assessments over the maximum 2-year follow-up period. Compared with 200 IU/day, 1,000+ IU/day was not associated with seated, standing, or orthostatic BP, and it did not lower risk of OH or orthostatic symptoms. Conclusions These findings do not support use of higher doses of vitamin D3 supplementation as an intervention to prevent OH. Clinical trials registration Trial Number NCT02166333. [ABSTRACT FROM AUTHOR]

Abstract Prior evidence suggests that vitamin D supplementation may reduce fall risk, but existing data are inconsistent and insufficient to guide policy. We designed a two-stage Bayesian response-adaptive dose-finding and seamless confirmatory randomized trial of vitamin D supplementation to prevent falls. Up to 1200 community-dwelling persons, aged ≥70 years, of predominantly white and African-American race, with serum 25(OH)D concentrations of 10–29 ng/mL and at elevated fall risk, will be randomized to one of four vitamin D3 (cholecalciferol) supplement doses: 200 (control), 1000, 2000, or 4000 IU/day and treated for up to 2 years. Stage 1 is designed to identify the best of the non-control doses for fall prevention. If a best dose is selected, Stage 2 will start seamlessly, with enrollees assigned to control or the best dose in Stage 1 continuing on that dose unchanged, enrollees assigned to the two non-control, non-best doses in Stage 1 switched to the best dose, and new enrollees randomly assigned 1:1 to control or the best dose. In Stage 2, we will compare the control dose group to the best dose group to potentially confirm the efficacy of that dose for fall prevention. The primary outcome measure in both stages is time to first fall or death, whichever comes first. Falls are ascertained from calendars, scheduled interviews, or interim self-reports. Secondary outcome measures include time to each component of the composite primary outcome and gait speed. Additional outcomes include the Short Physical Performance Battery score, physical activity level (assessed by accelerometry), and frailty score. Clinical Trial Registration: NCT02166333. [ABSTRACT FROM AUTHOR]

Introduction: Low physical activity is a criterion of phenotypic frailty defined as an increased state of vulnerability to adverse health outcomes. Whether disengagement from daily all-purpose physical activity is prospectively associated with frailty and possibly modified by chronic inflammation—a pathway often underlying frailty—remains unexplored. Methods: Using the Study to Understand Fall Reduction and Vitamin D in You data from 477 robust/prefrail adults (mean age = 76 ± 5 yr; 42% women), we examined whether accelerometer patterns (activity counts per day, active minutes per day, and activity fragmentation [broken accumulation]) were associated with incident frailty using Cox proportional hazard regression. Baseline interactions between each accelerometer metric and markers of inflammation that include interleukin-6, C-reactive protein, and tumor necrosis factor-alpha receptor 1 were also examined. Results: Over an average of 1.3 yr, 42 participants (9%) developed frailty. In Cox regression models adjusted for demographics, medical conditions, and device wear days, every 30 min·d−1 higher baseline active time, 100,000 more activity counts per day, and 1% lower activity fragmentation was associated with a 16% (P = 0.003), 13% (P = 0.001), and 8% (P < 0.001) lower risk of frailty, respectively. No interactions between accelerometer metrics and baseline interleukin-6, C-reactive protein, or tumor necrosis factor-alpha receptor 1 were detected (interaction P > 0.06 for all). Conclusions: Among older adults who are either robust or prefrail, constricted patterns of daily physical activity (i.e., lower total activity minutes and counts, and higher activity fragmentation) were prospectively associated with higher risk of frailty but not modified by frailty-related chronic inflammation. Additional studies, particularly trials, are needed to understand if this association is causal. [ABSTRACT FROM AUTHOR]