Rationale and design of the Study To Understand Fall Reduction and Vitamin D in You (STURDY): A randomized clinical trial of Vitamin D supplement doses for the prevention of falls in older adults

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.

Keywords: Adaptive Design; Aging; Falls; Randomized Trial; Vitamin D.

Copyright © 2018 Elsevier Inc. All rights reserved.

Figures

Figure 1.

Proposed biologic mechanisms for effects of vitamin D on reduction in falls

Figure 2.

Bayesian response-adaptive design: Schematics of two possible scenarios of response-adaptive randomizations to dose groups. Panel A: Scenario 1. A best dose is found during Stage 1 and that dose is compared to the control dose in Stage 2. Panel B: Scenario 2. Stage 1 dose-finding continues to the end of the trial with no best dose identified.