Ziegler Dan, Ametov Alexander, Barinov Alexey, Dyck Peter J, Gurieva Irina, Low Phillip A, Munzel Ullrich, Yakhno Nikolai, Raz Itamar, Novosadova Maria, Maus Joachim, Samigullin Rustem
FRCPE, Deutsche Diabetes-Klinik, Deutsches Diabetes-Zentrum, Leibniz-Institut an der Heinrich-Heine-Universität, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany.
Diabetes Care. 2006 Nov;29(11):2365-70. doi: 10.2337/dc06-1216.
The aim of this trial was to evaluate the effects of alpha-lipoic acid (ALA) on positive sensory symptoms and neuropathic deficits in diabetic patients with distal symmetric polyneuropathy (DSP).
In this multicenter, randomized, double-blind, placebo-controlled trial, 181 diabetic patients in Russia and Israel received once-daily oral doses of 600 mg (n = 45) (ALA600), 1,200 mg (n = 47) (ALA1200), and 1,800 mg (ALA1800) of ALA (n = 46) or placebo (n = 43) for 5 weeks after a 1-week placebo run-in period. The primary outcome measure was the change from baseline of the Total Symptom Score (TSS), including stabbing pain, burning pain, paresthesia, and asleep numbness of the feet. Secondary end points included individual symptoms of TSS, Neuropathy Symptoms and Change (NSC) score, Neuropathy Impairment Score (NIS), and patients' global assessment of efficacy.
Mean TSS did not differ significantly at baseline among the treatment groups and on average decreased by 4.9 points (51%) in ALA600, 4.5 (48%) in ALA1200, and 4.7 (52%) in ALA1800 compared with 2.9 points (32%) in the placebo group (all P < 0.05 vs. placebo). The corresponding response rates (>/=50% reduction in TSS) were 62, 50, 56, and 26%, respectively. Significant improvements favoring all three ALA groups were also noted for stabbing and burning pain, the NSC score, and the patients' global assessment of efficacy. The NIS was numerically reduced. Safety analysis showed a dose-dependent increase in nausea, vomiting, and vertigo.
Oral treatment with ALA for 5 weeks improved neuropathic symptoms and deficits in patients with DSP. An oral dose of 600 mg once daily appears to provide the optimum risk-to-benefit ratio.
本试验旨在评估α-硫辛酸（ALA）对糖尿病远端对称性多发性神经病变（DSP）患者感觉阳性症状和神经病变缺损的影响。
在这项多中心、随机、双盲、安慰剂对照试验中，俄罗斯和以色列的181例糖尿病患者在为期1周的安慰剂导入期后，接受每日一次口服600毫克（n = 45）（ALA600）、1200毫克（n = 47）（ALA1200）和1800毫克（ALA1800）的ALA（n = 46）或安慰剂（n = 43），持续5周。主要结局指标是总症状评分（TSS）相对于基线的变化，包括刺痛、灼痛、感觉异常和足部麻木。次要终点包括TSS的个体症状、神经病变症状与变化（NSC）评分、神经病变损害评分（NIS）以及患者对疗效的总体评估。
各治疗组在基线时的平均TSS无显著差异，与安慰剂组的2.9分（32%）相比，ALA600组平均下降4.9分（51%），ALA1200组下降4.5分（48%），ALA1800组下降4.7分（52%）（与安慰剂相比，均P < 0.05）。相应的缓解率（TSS降低≥50%）分别为62%、50%、56%和26%。在刺痛和灼痛、NSC评分以及患者对疗效的总体评估方面，也观察到所有三个ALA组均有显著改善。NIS在数值上有所降低。安全性分析显示，恶心、呕吐和眩晕呈剂量依赖性增加。
口服ALA治疗5周可改善DSP患者的神经病变症状和缺损。每日一次口服600毫克的剂量似乎能提供最佳的风险效益比。
