Trial reportThe Lancet. Neurology2011
Ascorbic acid in Charcot-Marie-Tooth disease type 1A (CMT-TRIAAL and CMT-TRAUK): a double-blind randomised trial.
Trial report in The Lancet. Neurology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 119 papers, 4 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
119 citing papers in PubMed, 4 syntheses or guidelines pooled it, 260 citations in OpenAlex.
- Targeted Therapies for Hereditary Peripheral Neuropathies: Systematic Review and Steps Towards a 'treatabolome'.Journal of neuromuscular diseases · 2021Pooled it
- Ascorbic acid for the treatment of Charcot-Marie-Tooth disease.The Cochrane database of systematic reviews · 2015Pooled it
- A meta-analysis of randomized double-blind clinical trials in CMT1A to assess the change from baseline in CMTNS and ONLS scales after one year of treatment.Orphanet journal of rare diseases · 2015Pooled it
- Interventions for fatigue in peripheral neuropathy.The Cochrane database of systematic reviews · 2014Pooled it
- A double-blind, placebo-controlled, randomized trial of PXT3003 for the treatment of Charcot-Marie-Tooth type 1A.Orphanet journal of rare diseases · 2021Trial
- Treadmill training in patients affected by Charcot-Marie-Tooth neuropathy: results of a multicenter, prospective, randomized, single-blind, controlled study.European journal of neurology · 2020Trial
- Nerve conduction velocity in CMT1A: what else can we tell?European journal of neurology · 2016Trial
- An exploratory randomised double-blind and placebo-controlled phase 2 study of a combination of baclofen, naltrexone and sorbitol (PXT3003) in patients with Charcot-Marie-Tooth disease type 1A.Orphanet journal of rare diseases · 2014Trial
- High-dosage ascorbic acid treatment in Charcot-Marie-Tooth disease type 1A: results of a randomized, double-masked, controlled trial.JAMA neurology · 2013Trial
- PXT3003: Lessons for therapeutic development in Charcot-Marie-Tooth disease type 1A and related neuropathies.iScience · 2026Review
- Myelination and Remyelination in Peripheral Nerve Injury: Mechanisms, Regulation, and Therapeutic Perspectives.MedComm · 2026Review
- A phase III clinical trial of PXT3003 in Chinese patients with Charcot-Marie-Tooth disease type 1A.iScience · 2026Article
- Quantifying Disease Progression in Patients With Charcot-Marie-Tooth Neuropathy Type 1A Using Quantitative Muscle MRI and Clinical Outcomes.Neurology · 2026Article
- Pathologic and Therapeutic Schwann Cells.Cells · 2025Review
- Nerve Diameter and DTI Parameters Maybe Potential Markers for Clinical Trial in Patients With Charcot-Marie-Tooth Disease Type 1A.European journal of neurology · 2025Article
- A Brief Review of Inherited Neuropathies: A Perspective from Saudi Arabia.Brain sciences · 2025Review
- Review
- Development of an initial training and evaluation programme for manual lower limb muscle MRI segmentation.European radiology experimental · 2024Article
- Advances and challenges in modeling inherited peripheral neuropathies using iPSCs.Experimental & molecular medicine · 2024Review
- Molecular mechanisms and therapeutic strategies for neuromuscular diseases.Cellular and molecular life sciences : CMLS · 2024Review
59 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
18 authors at 13 institutions in 3 countries.
Funding
Abstract
backgroundAscorbic 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.
methodsAdult 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).
findingsWe 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.
interpretationAscorbic 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.
fundingTelethon-UILDM and AIFA (Italian Medicines Agency) for CMT-TRIAAL, and Muscular Dystrophy Campaign for CMT-TRAUK.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.