Vitamin D Supplements to Prevent Falls in Older Adults: A Dose-Response Trial

描述(由申请人提供)：老年人跌倒造成的公共卫生负担很大。一些证据表明，维生素D补充剂可以显著降低跌倒的风险，对于血清25-羟基维生素D[25(OH)D]水平较低的人，可能会降低25%。然而，审判证据不足以指导政策。建议的研究是一项无缝、两阶段、贝叶斯反应自适应随机试验，用于剂量范围和疗效确认。这项试验旨在确定维生素D补充剂的最佳总剂量，并确认该剂量预防跌倒的疗效水平。参与者将是社区成年人，年龄70岁以上(~40%黑人，~60%女性)，基线血清25(OH)D水平为10-29 ng/ml，报告前一年至少有一次跌倒。在评价征聘战略和最后确定数据收集程序的初步PILT阶段之后，参与者将 随机分配到4种维生素D3(胆钙化醇)测试剂量中的一种：200IU、1000IU、2000IU和4000IU/d。参与者将服用他们分配的药片2年，并延长随访停药1年。该设计的第一阶段将在6米的随访期内选择预防跌倒的最佳剂量的维生素D。对照组(200iu)和最佳剂量组的参与者将继续无缝进入第二阶段，并对所有参与者进行额外的招募和持续的跟踪。主要结果(阶段2)是治疗2年后首次跌倒(或死亡)的时间。次要结果是跌倒发生率、跌倒模式、步态速度、平衡、肌肉力量、虚弱、SPPB评分，以及在参与者样本中的400米步行时间和加速度计。跌倒将从参与者每天完成的秋季日历中确定。后续访问将在3点、12点、24点和36点进行。具有差异化收益潜力的子组 补充维生素D的标准是预先规定的：a)种族(黑人和其他人)，b)基线维生素D水平(10-19vs20-29 ng/ml)，以及c)虚弱状态(虚弱、虚弱前、不虚弱)。我们有能力招募不同的人群，包括大量的黑人，这使我们能够在关键的亚群中测试补充维生素D的效果。这项研究的优势包括一支跨学科调查团队，他们在临床试验的设计、实施、分析和传播方面拥有丰富的经验和出色的记录，其中许多试验都有指导政策。调查团队包括具有维生素D代谢、内分泌学、老年病学、身体功能和跌倒评估、生物统计学、流行病学、中央实验室程序、适应性设计、社区参与和招募方面的专业知识的个人。根据我们在以前的社区试验中的记录，我们预计试验结果将是及时的、严格的，并与公共卫生指南直接相关，并将立即影响与老年人维生素D补充有关的预防跌倒政策。

DESCRIPTION (provided by applicant): The public health burden of falls in older persons is substantial. Several lines of evidence suggest that vitamin D supplements might substantially reduce the risk of falls, potentially by > 25% in persons with low serum 25-hydroxyvitamin D [25(OH)D] levels. However, trial evidence is insufficient to guide policy. The proposed study is a seamless, two stage, Bayesian response-adaptive randomized trial for dose-ranging and efficacy confirmation. The trial is designed to identify the best overall dose of vitamin D supplementation and confirm the level of efficacy of that dose for fall prevention. Participants wil be community-dwelling adults, aged 70+ (~40% black, ~60% women), with a baseline serum 25(OH)D level of 10-29 ng/ml, who report at least one fall in the prior year. After an initial pilt phase to evaluate recruitment strategies and finalize data collection procedures, participants will be randomly assigned to 1 of 4 vitamin D3 (cholecalciferol) test doses: 200IU, 1000IU, 2000IU and 4000IU/d. Participants will take their assigned pills for 2 years with extended follow-up off therapy for 1 more year. Stage 1 of this design will select the best dose of vitamin D for prevention of falls over a 6m follow-up period. Participants in the control (200IU) and best dose group will continue seamlessly into Stage 2 with additional recruitment and continued follow-up of all participants. The principal outcome (Stage 2) is time to first fall (or death) over 2 years f therapy. Secondary outcomes are fall rates, patterns of falling, gait speed, balance, muscle strength, frailty, SPPB score, and, in a sample of participants, 400m walk time and accelerometry. Falls will be ascertained from fall calendars completed daily by participants. Follow-up visits will occur at 3, 12, 24 and 36m. Subgroups with potential for differential benefit from vitamin D supplementation are pre- specified as: a) race (blacks vs others), b) baseline vitamin D levels (10-19 vs 20-29ng/ml), and c) frailty status (frail, pre-frail, not frail). Our prven capacity to recruit a diverse population, including large numbers of blacks, allows us to test the effects of vitamin D supplementation in key subgroups. Strengths of the study include a team of interdisciplinary investigators who have vast experience and an exceptional track record in the design, conduct, analysis and dissemination of clinical trials, many of which have guided policy. The investigative team includes individuals with expertise in vitamin D metabolism, endocrinology, geriatrics, assessment of physical function and falls, biostatistics, epidemiology, central laboratory procedures, adaptive designs, community engagement, and recruitment. Building on our record in previous community-based trials, we expect that trial results will be timely, rigorous, and directly relevant to public health guidelines and will immediately influence fall prevention policies related to vitamin D supplementation in older persons.