Randomised controlled trial dataset: efficacy and safety of ascorbic acid (Vitamin C) supplementation for children with Charcot-Marie-Tooth disease type 1A

This randomised controlled trial dataset is an output of an investigation into the efficacy and safety of ascorbic acid (Vitamin C) supplementation for children with Charcot-Marie-Tooth disease type 1A (CMT1A) . The purpose of this double-blind trial was to determine the effect of high-dose vitamin C on muscle strength, nerve function, gross motor coordination and health-related quality of life in children with CMT1A.

Background: CMT1A is the most common inherited nerve disorder. CMT1A is characterised by peripheral nerve demyelination, weakness, and impaired motor function and is caused by the duplication of the gene that encodes peripheral myelin protein 22 (PMP22). High-dose ascorbic acid has been shown to have remyelinating potential and to correct the phenotype of a transgenic mouse model of CMT1A by decreasing expression of PMP22. The efficacy and safety of ascorbic acid supplementation in children with CMT1A was tested.

Methods: This 12-month, randomised, double-blind, placebo-controlled trial was undertaken between June 2007 and December 2008, and assessed high-dose oral ascorbic acid (about 30 mg/kg/day) in 81 children with CMT1A (2-16 years). Randomisation was done on a 1:1 ratio by a computer-generated algorithm. All investigators and participants were blinded to treatment allocation with the exception of the trial pharmacist. The primary efficacy outcome was median nerve motor conduction velocity (m/s) at 12 months. Secondary outcomes were foot and hand strength, motor function, walking ability, and quality of life. Compliance was measured by plasma ascorbic acid concentration, pill count, and medication diary entries. Analysis was by intention to treat.

Findings: 81 children were randomly assigned to receive high-dose ascorbic acid (n=42) or placebo (n=39). 80 children completed 12 months of treatment. The ascorbic acid group had a small, non-significant increase in median nerve motor conduction velocity compared with the placebo group (adjusted mean difference 1.7 m/s, 95% CI -0.1 to 3.4; p=0.06). There was no measurable effect of ascorbic acid on neurophysiological, strength, function, or quality of life outcomes. Two children in the ascorbic acid group and four children in the placebo group reported gastrointestinal symptoms. There were no serious adverse events.

Interpretation: 12 months of treatment with high-dose ascorbic acid was safe and well tolerated but none of the expected efficacy endpoints were reached.

Data format: Data was collected in .csv and excel spreadsheets, and analysed using SPSS. The dataset contains identifying information, but may be de-identified for future reuse, if ethical conditions are met.

This description is drawn from the summary in the Australian New Zealand Clinical Trials Registry (ANZCTR) and associated publications. For further information regarding this dataset, please refer to the summary in the ANZCTR Registry and associated publications below.

本随机对照试验数据集是一项针对1A型腓骨肌萎缩症（Charcot-Marie-Tooth disease type 1A, CMT1A）儿童患者补充抗坏血酸（维生素C，ascorbic acid）的疗效与安全性研究的产出成果。本项双盲试验旨在探究大剂量维生素C对CMT1A儿童患者的肌肉力量、神经功能、粗大运动协调能力以及健康相关生活质量的影响。

背景：CMT1A是最常见的遗传性神经疾病，以周围神经脱髓鞘、肌无力及运动功能受损为特征，由编码周围髓鞘蛋白22（peripheral myelin protein 22, PMP22）的基因重复突变所致。已有研究表明，大剂量抗坏血酸具备髓鞘再生潜力，可通过降低PMP22的表达，纠正CMT1A转基因小鼠模型的表型。本研究旨在评估CMT1A儿童患者补充抗坏血酸的疗效与安全性。

方法：本试验为为期12个月的随机双盲安慰剂对照研究，于2007年6月至2008年12月间开展，共纳入81名2~16岁的CMT1A儿童患者，受试对象每日口服大剂量抗坏血酸（约30mg/kg/天）。采用计算机生成算法按1:1比例进行随机分组。除试验药师外，所有研究人员与受试者均对治疗分配不知情。本研究的主要疗效终点为12个月时的正中神经运动传导速度（单位：m/s）；次要疗效终点包括手足肌力、运动功能、行走能力及生活质量。依从性通过血浆抗坏血酸浓度、药片计数及用药日记进行评估。数据分析采用意向性治疗分析方法。

结果：共81名儿童被随机分配至大剂量抗坏血酸组（n=42）与安慰剂组（n=39），其中80名儿童完成了12个月的治疗。与安慰剂组相比，抗坏血酸组患者的正中神经运动传导速度出现小幅且无统计学意义的提升（校正均数差为1.7m/s，95%置信区间：-0.1~3.4；p=0.06）。未观察到抗坏血酸对神经生理学、肌力、运动功能或生活质量指标存在可测量的影响。抗坏血酸组有2名儿童、安慰剂组有4名儿童报告了胃肠道症状，未发生严重不良事件。

解读：为期12个月的大剂量抗坏血酸治疗安全性良好且耐受性佳，但未达到预设的所有疗效终点。

数据格式：研究数据以.csv及Excel电子表格形式收集，并使用SPSS软件进行分析。本数据集包含识别信息，在满足伦理条件的前提下，可进行去标识化处理以供后续复用。

本描述源自澳大利亚新西兰临床试验注册中心（Australian New Zealand Clinical Trials Registry, ANZCTR）的摘要及相关发表文献。如需了解本数据集的更多信息，请参阅ANZCTR注册平台及下述相关发表文献的摘要。