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

描述（由申请人提供）：老年人福尔斯的公共卫生负担是巨大的。几条证据表明，维生素D补充剂可能会大大降低福尔斯的风险，在血清25-羟基维生素D [25（OH）D]水平低的人群中可能降低25%以上。然而，审判证据不足以指导政策。拟定的研究是一项无缝、两阶段、贝叶斯反应适应性随机试验，用于剂量范围确定和疗效确认。该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有效性水平。参与者将是居住在社区的成年人，年龄70岁以上（约40%黑人，约60%女性），基线血清25（OH）D水平为10-29 ng/ml，在前一年至少报告一次跌倒。 在评估招聘战略和完成数据收集程序的初始试点阶段之后，参与者将 随机分配至4种维生素D3（胆钙化醇）试验剂量之一：200 IU、1000 IU、2000 IU和4000 IU/d。受试者将服用分配的药物2年，并延长随访1年。该设计的第1阶段将选择在6个月随访期内预防福尔斯跌倒的最佳维生素D剂量。对照组（200 IU）和最佳剂量组的受试者将继续无缝进入第2阶段，并对所有受试者进行额外招募和持续随访。主要结局（第2阶段）是治疗2年内首次跌倒（或死亡）的时间。次要结果是跌倒率、跌倒模式、步态速度、平衡、肌肉力量、虚弱、SPPB评分，以及参与者样本中的400米步行时间和加速度计。福尔斯将从参与者每天完成的秋季日历中确定。随访访视将在3、12、24和36个月进行。有可能获得不同惠益的亚组 维生素D补充剂中的维生素D水平预先规定为：a）种族（黑人对其他人），B）基线维生素D水平（10-19对20- 29 ng/ml），和c）虚弱状态（虚弱、虚弱前期、不虚弱）。我们招募包括大量黑人在内的多样化人群的能力使我们能够在关键亚组中测试维生素D补充剂的效果。 该研究的优势包括一个跨学科的研究人员团队，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卓越的记录，其中许多都指导了政策。调查小组包括在维生素D代谢、内分泌学、老年病学、身体功能和福尔斯评估、生物统计学、流行病学、中心实验室程序、适应性设计、社区参与和招募方面具有专业知识的个人。基于我们在以前的社区试验中的记录，我们预计试验结果将及时，严格，并与公共卫生指南直接相关，并将立即影响与老年人补充维生素D相关的跌倒预防政策。

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.