Ziegler D, Hanefeld M, Ruhnau K J, Meissner H P, Lobisch M, Schütte K, Gries F A
Diabetes-Forschungsinstitut an der Heinrich-Heine-Universität, Düsseldorf, Germany.
Diabetologia. 1995 Dec;38(12):1425-33. doi: 10.1007/BF00400603.
Anti-oxidant treatment has been shown to prevent nerve dysfunction in experimental diabetes mellitus, thus providing a rationale of potential therapeutic value for diabetic patients. The effects of the anti-oxidant alpha-lipoic acid (thioctic acid) were studied in a 3-week multicentre, randomized, double-blind placebo-controlled trial (Alpha-Lipoic Acid in Diabetic Neuropathy; ALADIN) in 328 non-insulin-dependent diabetic patients with symptomatic peripheral neuropathy who were randomly assigned to treatment with intravenous infusion of alpha-lipoic acid using three doses (1200, 600, or 100 mg ALA) or placebo (PLAC). Neuropathic symptoms (pain, burning, paraesthesiae, and numbness) were scored at baseline and at each visit (days 2-5, 8-12, and 15-19) prior to infusion. In addition, the Hamburg Pain Adjective List, a multidimensional specific pain questionnaire, and the Neuropathy Symptom and Disability Scores were assessed at baseline and day 19. According to the protocol 260 (65/63/66/66) patients completed the study. The total symptom score in the feet decreased from baseline to day 19 by -4.5 +/- 3.7 (-58.6%) points (mean +/- SD) in ALA 1200, -5.0 +/- 4.1 (-63.5%) points in ALA 600, -3.3 +/- 2.8 (-43.2%) points in ALA 100, and -2.6 +/- 3.2 (-38.4%) points in PLAC (ALA 1200 vs PLAC: p = 0.003; ALA 600 vs PLAC: p < 0.001). The response rates after 19 days, defined as an improvement in the total symptom score of at least 30%, were 70.8% in ALA 1200, 82.5% in ALA 600, 65.2% in ALA 100, and 57.6% in PLAC (ALA 600 vs PLAC; p = 0.002). The total scale of the Pain Adjective List was significantly reduced in ALA 1200 and ALA 600 as compared with PLAC after 19 days (both p < 0.01). The rates of adverse events were 32.6% in ALA 1200, 18.2% in ALA 600, 13.6% in ALA 100, and 20.7% in PLAC. These findings substantiate that intravenous treatment with alpha-lipoic acid using a dose of 600 mg/day over 3 weeks is superior to placebo in reducing symptoms of diabetic peripheral neuropathy, without causing significant adverse reactions.
抗氧化治疗已被证明可预防实验性糖尿病中的神经功能障碍，从而为糖尿病患者提供了具有潜在治疗价值的理论依据。在一项为期3周的多中心、随机、双盲、安慰剂对照试验（糖尿病神经病变中的α-硫辛酸；ALADIN）中，研究了抗氧化剂α-硫辛酸（硫辛酸）对328例有症状性周围神经病变的非胰岛素依赖型糖尿病患者的影响，这些患者被随机分配接受静脉输注三种剂量（1200、600或100mg ALA）的α-硫辛酸或安慰剂（PLAC）治疗。在基线时以及每次输注前的就诊时（第2 - 5天、第8 - 12天和第15 - 19天）对神经病变症状（疼痛、烧灼感、感觉异常和麻木）进行评分。此外，在基线和第19天评估了汉堡疼痛形容词列表（一种多维特异性疼痛问卷）以及神经病变症状和残疾评分。根据方案，260例（65/63/66/66）患者完成了研究。在第19天时，1200mg ALA组足部总症状评分较基线下降了-4.5±3.7（-58.6%）分（平均值±标准差），600mg ALA组下降了-5.0±4.1（-63.5%）分，100mg ALA组下降了-3.3±2.8（-43.2%）分，安慰剂组下降了-2.6±3.2（-38.4%）分（1200mg ALA组与安慰剂组比较：p = 0.003；600mg ALA组与安慰剂组比较：p < 0.001）。第19天后的缓解率定义为总症状评分至少改善30%，1200mg ALA组为70.8%，600mg ALA组为82.5%，100mg ALA组为65.2%，安慰剂组为57.6%（600mg ALA组与安慰剂组比较；p = 0.002）。与安慰剂组相比，19天后1200mg ALA组和600mg ALA组的疼痛形容词列表总分显著降低（均p < 0.01）。不良事件发生率在1200mg ALA组为32.6%，600mg ALA组为18.2%，100mg ALA组为13.6%，安慰剂组为20.7%。这些发现证实，在3周内每天静脉注射600mg剂量的α-硫辛酸在减轻糖尿病周围神经病变症状方面优于安慰剂，且不会引起明显的不良反应。
