Effect of ascorbic acid in patients with Charcot-Marie-Tooth disease type 1A: a multicentre, randornised, double-blind, placebo-control led trial
Effect of ascorbic acid in patients with Charcot-Marie-Tooth disease type 1A: a multicentre, randornised, double-blind, placebo-control led trial
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抗坏血酸对 1A 型夏科-玛丽-牙病患者的影响：一项多中心、随机、双盲、安慰剂对照试验
DOI：
10.1016/s1474-4422(09)70260-1
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发表时间：
2009-12-01
期刊：
影响因子：
48
通讯作者：
Blin, Olivier
中科院分区：
文献类型：
--
作者：
Micallef, Joelle;Attarian, Shahram;Blin, Olivier
背景 1A 型腓骨肌萎缩症 (CMT1A) 是一种遗传性周围神经病，大约每 5000 名新生儿中就有一人受到影响。尽管抗坏血酸已被证明可以在 CMT1A 转基因小鼠模型中减少脱髓鞘并改善肌肉功能，但目前尚无针对这种退行性疾病的具体疗法，其特点是远端进行性肌肉萎缩和感觉丧失。我们测试了抗坏血酸对成人 CMT1A 的安全性和有效性。方法这项为期 12 个月的随机、双盲、安慰剂对照研究于 2005 年 9 月至 2008 年 10 月进行。根据临床检查和基因分型确认诊断为 CMT1A 的患者按 1:1:1 的比例随机分配，接受每天 1 g 抗坏血酸、每天 3 g 抗坏血酸、或安慰剂。治疗分配基于计算机生成的随机数列表，每组 12 个，并根据研究地点和性别进行分层；所有研究人员和参与者都不知道治疗分配。主要结局是 12 个月时的腓骨肌萎缩症神经病变评分 (CMTNS)。分析是按意向治疗进行的。这项研究已在 Orphanet 数据库注册，编号为 ORPHA60779。 结果 安慰剂组 (n=62) 的 CMTNS 从基线到 12 个月的中位变化为 0.5 分（95% CI -0.3 至 1.4），1 g 抗坏血酸组（n=56）为 0.7 分（0.0 至 1.4），为 -0.4 分（-1.2 至 1.4）。 0.4) 对于 3 g 抗坏血酸基团 (n=61)。我们没有发现各组之间的这些变化有任何显着差异（p=0.14）。各组之间不良事件的发生率没有差异 (p=0.74)。 解释 对于 12 个月以上的 CMT1A 成人患者，两种剂量的抗坏血酸都是安全的且耐受性良好。然而，各组之间没有显着差异，并且未显示抗坏血酸的功效。
Background Charcot-Marie-Tooth disease type 1A (CMT1A) is a hereditary peripheral neuropathy that affects roughly one in 5000 births. No specific therapy currently exists for this degenerative disorder, which is characterised by distal progressive muscle atrophy and sensory loss, although ascorbic acid has been shown to reduce demyelination and improve muscle function in a transgenic mouse model of CMT1A. We tested the safety and efficacy of ascorbic acid in adults with CMT1A.Methods This 12-month, randomised, double-blind, placebo-controlled study was undertaken between September, 2005, and October, 2008. Patients diagnosed with CMT1A according to clinical examination and confirmation by genotyping were randomly assigned in a 1:1:1 ratio to receive 1 g ascorbic acid per day, 3 g ascorbic acid per day, or placebo. Treatment allocation was based on a computer-generated list of random numbers in blocks of 12, with stratification according to study site and sex; all investigators and participants were unaware of treatment allocation. The primary outcome was the Charcot-Marie-Tooth disease neuropathy score (CMTNS) at 12 months. Analysis was by intention to treat. This study is registered with the Orphanet Database, number ORPHA60779.Findings The median change in CMTNS from baseline to 12 months was 0.5 points (95% CI -0.3 to 1.4) for the placebo group (n=62), 0.7 points (0.0 to 1.4) for the 1 g ascorbic acid group (n=56), and -0.4 points (-1.2 to 0.4) for the 3 g ascorbic acid group (n=61). We did not find any significant difference in these changes between the groups (p=0.14). The occurrence of adverse events did not differ between the groups (p=0.74).Interpretation Ascorbic acid at both doses was safe and well tolerated in adults with CMT1A over 12 months. However, there were no significant differences between the groups and the efficacy of ascorbic acid was not shown.