Phocean Institute of Nephrology, Marseille, France.
ELSAN, Clinique Bouchard, Marseille, France.
Trials. 2021 May 25;22(1):364. doi: 10.1186/s13063-021-05302-9.
Muscle strength decreases as kidney failure progresses. Low muscle strength affects more than 50% of hemodialysis patients and leads to daily life activities impairment. In the general population, numerous studies have linked low 25OH-vitamin D (25OHD) concentrations to the loss of the muscle strength and low physical performances. Data on native vitamin D and muscle function are scarce in the chronic kidney disease (CKD) population, but low 25OHD levels have been associated with poor muscle strength. We present in this article the protocol of an ongoing study named VITADIAL testing if cholecalciferol supplementation in hemodialysis patients with low 25OHD improves their muscle strength.
METHODS/DESIGN: VITADIAL is a prospective open randomized French multicenter study. All patients will have 25OHD levels ≤50nmol/L at randomization. One group will receive 100,000 UI cholecalciferol once a month during 6 months; the other group will receive no treatment during 6 months. In order to randomize patients with 25OHD ≤50nmol/L, supplemented patients will undergo a 3 months wash-out period renewable 3 times (maximum of 12 months wash-out) until 25OHD reaches a level ≤50nmol/L. The main objective of this study is to analyze if a 6-month period of oral cholecalciferol (i.e., native vitamin D) supplementation improves muscle strength of hemodialysis patients with low 25OHD vitamin D levels. Muscle strength will be assessed at 0, 3, and 6 months, by handgrip strength measured with a quantitative dynamometer. Secondary objectives are (1) to analyze 25OHD plasma levels after vitamin D wash-out and/or supplementation, as well as factors associated with 25OHD lowering speed during wash-out, and (2) to analyze if this supplementation improves patient's autonomy, reduces frailty risk, and improves quality of life. Fifty-four patients are needed in each group to meet our main objective.
In the general population, around 30 randomized studies analyzed the effects of vitamin D supplementation on muscle strength. These studies had very different designs, sizes, and studied population. Globally, these studies and the meta-analysis of studies favor a beneficial effect of vitamin D supplementation on muscle strength, but this effect is mainly found in the subgroup of aged patients and those with the lowest 25OHD concentrations at inclusion. We reported a positive independent association between 25OHD and handgrip strength in a population of 130 hemodialysis patients in a dose-dependent manner. In our cohort, a plateau effect was observed above 75 nmol/L. Only two randomized studies analyzed the effect of native vitamin D supplementation on muscle strength in hemodialysis patients, but unfortunately, these two studies were underpowered. VITADIAL is a trial specifically designed to assess whether cholecalciferol might benefit to hemodialysis patient's muscle strength.
ClinicalTrials.gov NCT04262934 . Registered on 10 February 2020 - Retrospectively registered.
随着肾功能衰竭的进展，肌肉力量会下降。肌肉力量低下影响超过 50%的血液透析患者，并导致日常生活活动受损。在普通人群中，大量研究表明，低 25 羟维生素 D（25OHD）浓度与肌肉力量丧失和身体机能下降有关。在慢性肾脏病（CKD）人群中，关于天然维生素 D 和肌肉功能的数据很少，但低 25OHD 水平与肌肉力量差有关。我们在本文中介绍了一项正在进行的研究的方案，该研究名为 VITADIAL，旨在研究补充胆钙化醇是否可以改善血液透析患者的肌肉力量。
方法/设计：VITADIAL 是一项前瞻性、开放、随机的法国多中心研究。所有患者在随机分组时 25OHD 水平均≤50nmol/L。一组患者每月接受 100,000IU 胆钙化醇治疗 6 个月；另一组在 6 个月内不接受治疗。为了随机分组 25OHD≤50nmol/L 的患者，补充组患者将进行为期 3 个月的洗脱期，最多可进行 3 次（最长洗脱期为 12 个月），直到 25OHD 水平达到≤50nmol/L。该研究的主要目的是分析 6 个月的口服胆钙化醇（即天然维生素 D）补充是否可以改善 25OHD 维生素 D 水平低的血液透析患者的肌肉力量。肌肉力量将在 0、3 和 6 个月时使用定量测力计测量握力进行评估。次要目标是（1）分析维生素 D 洗脱和/或补充后的 25OHD 血浆水平，以及与洗脱过程中 25OHD 降低速度相关的因素，以及（2）分析这种补充是否可以提高患者的自主性、降低脆弱风险和改善生活质量。每组需要 54 例患者以满足我们的主要目标。
在普通人群中，大约有 30 项随机研究分析了维生素 D 补充对肌肉力量的影响。这些研究设计、规模和研究人群都非常不同。总体而言，这些研究和对研究的荟萃分析都支持维生素 D 补充对肌肉力量有益，但这种作用主要在年龄较大的患者亚组和纳入时 25OHD 浓度最低的患者亚组中发现。我们在 130 名血液透析患者的人群中报告了 25OHD 与握力之间呈剂量依赖性的正相关关系。在我们的队列中，观察到 75nmol/L 以上出现平台效应。只有两项随机研究分析了天然维生素 D 补充对血液透析患者肌肉力量的影响，但不幸的是，这两项研究的样本量都不足。VITADIAL 是一项专门设计的研究，旨在评估胆钙化醇是否可能有益于血液透析患者的肌肉力量。
ClinicalTrials.gov NCT04262934。2020 年 2 月 10 日注册-回顾性注册。
