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      Ascorbic acid in Charcot–Marie–Tooth disease type 1A (CMT-TRIAAL and CMT-TRAUK): a double-blind randomised trial

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          Summary Background Ascorbic acid reduced the severity of neuropathy in transgenic mice overexpressing peripheral myelin protein 22 (PMP22), a model of Charcot–Marie–Tooth disease type 1A (CMT1A) associated with the PMP22 duplication. However, in three 1-year trials, ascorbic acid had no benefit in human beings. We did a multicentre 2-year trial to test the efficacy and tolerability of ascorbic acid in patients with CMT1A. Methods Adult patients (aged 18–70 years) with symptomatic CMT1A were enrolled from nine centres in Italy and the UK, and were randomly assigned (1:1 ratio) to receive 1·5 g/day oral ascorbic acid or matching placebo for 24 months. The randomisation sequence was computer generated by block randomisation, stratified by centre and disease severity, and patients were allocated to treatment by telephone. The primary outcome was change in the CMT neuropathy score (CMTNS) at 24 months. Secondary outcomes were timed 10 m walk test, nine-hole peg test, overall neuropathy limitations scale, distal maximal voluntary isometric contraction, visual analogue scales for pain and fatigue, 36-item short-form questionnaire, and electrophysiological measurements. Patients, treating physicians, and physicians assessing outcome measures were masked to treatment allocation. Analysis of the primary outcome was done on all randomised patients who received at least one dose of study drug. This study is registered, numbers ISRCTN61074476 (CMT-TRAUK) and EudraCT 2006-000032-27 (CMT-TRIAAL). Findings We enrolled and randomly assigned 277 patients, of whom six (four assigned to receive ascorbic acid) withdrew consent before receiving treatment; 138 receiving ascorbic acid and 133 receiving placebo were eligible for analysis. Treatment was well tolerated: 241 of 271 patients (89% in each group) completed the study; 20 patients (nine receiving ascorbic acid) dropped out because of adverse events. Mean CMTNS at baseline with missing data imputed was 14·7 (SD 4·8) in the ascorbic acid group and 13·9 (4·2) in the placebo group. Mean worsening of CMTNS was 0·2 (SD 2·8, 95% CI −0·3 to 0·7) in the ascorbic acid group and 0·2 (2·7, −0·2 to 0·7) in the placebo group (mean difference 0·0, 95% CI −0·6 to 0·7; p=0·93). We recorded no differences between the groups for the secondary outcomes at 24 months. 21 serious adverse events occurred in 20 patients, eight in the ascorbic acid group and 13 in the placebo group. Interpretation Ascorbic acid supplementation had no significant effect on neuropathy compared with placebo after 2 years, suggesting that no evidence is available to support treatment with ascorbic acid in adults with CMT1A. Funding Telethon-UILDM and AIFA (Italian Medicines Agency) for CMT-TRIAAL, and Muscular Dystrophy Campaign for CMT-TRAUK.

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              This article reports on the development and validation of the Italian SF-36 Health Survey using data from seven studies in which an Italian version of the SF-36 was administered to more than 7000 subjects between 1991 and 1995. Empirical findings from a wide array of studies and diseases indicate that the performance of the questionnaire improved as the Italian translation was revised and that it met the standards suggested by the literature in terms of feasibility, psychometric tests, and interpretability. This generally satisfactory picture strengthens the idea that the Italian SF-36 is as valid and reliable as the original instrument and applicable and valid across age, gender, and disease. Empirical evidence from a cross-sectional survey carried out to norm the final version in a representative sample of 2031 individuals confirms the questionnaire's characteristics in terms of hypothesized constructs and psychometric behavior and gives a better picture of its external validity (i.e., robustness and generalizability) when administered in settings that are very close to real world.
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                Author and article information

                Journal
                The Lancet Neurology
                The Lancet Neurology
                Elsevier BV
                14744422
                April 2011
                April 2011
                : 10
                : 4
                : 320-328
                Article
                10.1016/S1474-4422(11)70025-4
                4d5415bf-6267-4737-8f89-f97ca46f8a27
                © 2011

                https://www.elsevier.com/tdm/userlicense/1.0/

                http://creativecommons.org/licenses/by/4.0/

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