Earley Christopher J, Horská Alena, Mohamed Mona A, Barker Peter B, Beard John L, Allen Richard P
Department of Neurology, Johns Hopkins University, Johns Hopkins Bayview Medical Center, 5501 Hopkins Bayview Circle, AAC 1B-82, Baltimore, MD 21224, USA.
Sleep Med. 2009 Feb;10(2):206-11. doi: 10.1016/j.sleep.2007.12.006. Epub 2008 Feb 14.
The aim of this study was to ascertain whether high-dose intravenous (IV) iron sucrose could improve symptoms and change brain iron concentrations in idiopathic RLS.
The study was a randomized, parallel-group double-blind study of 1000mg iron sucrose given IV versus placebo. Primary measures of the clinical status were global rating scale (GRS) and periodic leg movements of sleep (PLMS). Primary measures of brain iron status were CSF ferritin and MRI-determined iron in the substantia nigra.
At the time of the interim analysis there were 7 placebo and 11 iron-treated subjects. At 2-weeks post-treatment, iron treatment resulted in a small but significant increase in CSF ferritin and a decrease in RLS severity (GRS) but did not change PLMS or MRI iron index. None of the secondary outcomes changed with treatment. There was no single case of clear treatment benefit in any of the patients. This interim analysis revealed an effect size that was too small to allow for adequate power to find significant differences with the planed 36-subject enrollment for either the primary objective outcome of PLMS or any of the secondary outcomes. The study was stopped at this planned break-point given the lack of both adequate power and any indication for clinically significant benefit.
High-dose IV iron failed to demonstrate the robust changes reported in three prior open-label studies. Differences in iron formulation, dosing regiment, and peripheral iron status may explain some of the discrepancies between this and previous IV iron treatment studies.
本研究旨在确定高剂量静脉注射蔗糖铁是否能改善特发性不宁腿综合征的症状并改变脑铁浓度。
本研究为一项随机、平行组双盲研究，比较静脉注射1000mg蔗糖铁与安慰剂的效果。临床状态的主要测量指标为总体评定量表（GRS）和睡眠期周期性腿部运动（PLMS）。脑铁状态的主要测量指标为脑脊液铁蛋白和通过MRI测定的黑质铁含量。
在中期分析时，有7名接受安慰剂治疗的受试者和11名接受铁剂治疗的受试者。治疗后2周，铁剂治疗使脑脊液铁蛋白有小幅但显著的升高，不宁腿综合征严重程度（GRS）降低，但未改变PLMS或MRI铁指数。没有任何次要结局指标因治疗而改变。没有一例患者有明确的治疗获益。本次中期分析显示效应量过小，以至于按照计划纳入36名受试者时，无论是PLMS的主要目标结局还是任何次要结局，都没有足够的检验效能来发现显著差异。鉴于缺乏足够的检验效能以及没有临床显著获益的迹象，该研究在这个计划的断点处停止。
高剂量静脉注射铁剂未能显示出之前三项开放标签研究中所报道的显著变化。铁剂配方、给药方案和外周铁状态的差异可能解释了本研究与之前静脉注射铁剂治疗研究之间的一些差异。
