Vitamin D Supplementation on Physical and Cognitive Function-Pilot Study

描述（由申请人提供）： 血液透析（HD）患者循环中1，25-OH维生素D水平降低，因为其主要生产部位是通过1-α羟化酶的健康肾脏。缺乏症在透析时用静脉注射1，25-OH活性维生素D治疗，滴定以达到国家肾脏基金会（NKF）肾透析结果质量倡议（KDOQI）指南推荐的目标甲状旁腺激素（PTH）值。尽管有这些静脉维生素D治疗，HD患者25-OH维生素缺乏症的患病率非常高。在非透析人群中，25-OH缺乏症与神经肌肉功能和认知能力差相关。目前尚不清楚维生素25-OH D缺乏在HD患者经历的高度普遍的肌无力和认知障碍中的作用。由于肾脏以外的许多组织具有能够将25 OH维生素D活化为1-25 OH维生素D的1-α羟化酶，因此仅针对PTH范围给予IV活性维生素D可能完全忽略其他骨骼外组织上的重要维生素D。我们研究的主要目的是确定维生素D补充对25-OH维生素D水平< 20 ng/ml的HD患者神经肌肉和认知功能的影响。我们提出一项前瞻性、随机、[双盲安慰剂对照]试验。入组的受试者将以2：1的比例随机接受维生素D（n=20）或[安慰剂]（n=10）治疗6个月。在基线神经肌肉和认知评估后，治疗组将每两周接受50，000 IU口服麦角钙化醇，持续6个月，并每月重新测量25（OH）维生素D3水平。补充维生素D 6个月后，将进行神经肌肉和认知评估。将分析[安慰剂]组和治疗组之间的神经肌肉功能和认知评估结果，以及两组6个月间隔前后的评估差异。 公共卫生相关性： James J. Peters VAMC的门诊HD部门在过去两年中每年增长近15%，是最大的VA透析中心之一。肌无力和认知障碍在HD患者中很常见，可能导致该人群中福尔斯的高患病率。福尔斯导致发病率增加，独立性降低，并可能增加死亡率。虽然认知障碍可能导致福尔斯跌倒，但也可能导致HD患者对复杂药物治疗和药物治疗方案的依从性差。鉴于维生素D治疗的安全性、低成本和潜在的临床益处，我们提出了一项研究来评估其在改善重要临床终点方面的作用。

DESCRIPTION (provided by applicant): Hemodialysis (HD) patients have reduced circulating levels of 1,25-OH vitamin D levels because its major site of production is the healthy kidney via the 1-alpha hydroxylase enzyme. The deficiency is treated with intravenous1,25-OH active vitamin D at dialysis which is titrated to achieve a targeted parathyroid hormone (PTH) value recommended by the National Kidney Foundation (NKF) Kidney Dialysis Outcomes Quality Initiative (KDOQI) Guidelines. Despite these intravenous vitamin D treatments, HD patients have a very high prevalence of 25-OH vitamin deficiency. 25-OH deficiency has been associated with poor neuromuscular function and cognition in non-dialysis populations. The role vitamin 25-OH D deficiency in the highly prevalent muscle weakness and cognitive impairment experienced by HD patients is currently not known. Since many tissues other than the kidney possess the 1-alpha hydroxylase enzyme capable of activating 25 OH vitamin D to 1-25 OH vitamin D, administering IV active vitamin D solely to target a PTH range may completely neglect important vitamin D on other extra-skeletal tissues. The primary goal of our study is to determine the effect of vitamin D supplementation on neuromuscular and cognitive function in HD patients with 25-OH vitamin D levels < 20 ng/ml. We propose a prospective, randomized, [double-blind placebo controlled] trial. Enrolled participants will be randomized 2:1 to receive vitamin D (n=20) or [placebo] (n=10) for 6 months. Following baseline neuromuscular and cognitive assessments, the treatment group will receive 50,000 IU of oral ergocalciferol every two weeks for 6 months, and have 25(OH) vitamin D3 levels re-measured at monthly intervals. Following 6 months of vitamin D supplementation, neuromuscular and cognitive assessments will be performed. Results from neuromuscular function and cognitive assessments between the [placebo] arm and treatment will be analyzed as well as differences in assessments prior to and following the 6 month interval in both groups. PUBLIC HEALTH RELEVANCE: The outpatient HD unit at the James J. Peters VAMC has grown nearly 15% each year for the past two years and is one of the largest VA dialysis centers. Muscle weakness and cognitive impairment are common among HD patients and likely contributes to the high prevalence of falls in this population. Falls result in increased morbidity, decreased independence, and likely increases mortality. While cognitive impairment can contribute to falls it is also likely to result in poor compliance with complex medical treatments and medication regimens required of HD patients. Given the safety, low cost of supplementation, and potential clinical benefits of vitamin D treatment, we propose a study to evaluate its role in improving important clinical endpoints.