Trial reportJAMA neurology2013
High-dosage ascorbic acid treatment in Charcot-Marie-Tooth disease type 1A: results of a randomized, double-masked, controlled trial.
Trial report in JAMA neurology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT00484510 (A Randomized, Placebo-controlled, Double Masked 120 Subject "Futility Design" Clinical Trial of Ascorbic Acid Treatment of Charcot Marie Tooth Disease Type 1A.), which is not on this map. Cited by 71 papers, 3 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.
A Randomized, Placebo-controlled, Double Masked 120 Subject "Futility Design" Clinical Trial of Ascorbic Acid Treatment of Charcot Marie Tooth Disease Type 1A.
Who cites it
71 citing papers in PubMed, 3 syntheses or guidelines pooled it, 129 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
- Randomized trial of l-serine in patients with hereditary sensory and autonomic neuropathy type 1.Neurology · 2019Trial
- 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
- A phase III clinical trial of PXT3003 in Chinese patients with Charcot-Marie-Tooth disease type 1A.iScience · 2026Article
- Pathologic and Therapeutic Schwann Cells.Cells · 2025Review
- Review
- 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
- Lower limb muscle MRI fat fraction is a responsive outcome measure in CMT X1, 1B and 2A.Annals of clinical and translational neurology · 2024Article
- Article
- Evaluating plasma biomarkers NfL, GFAP, GDF15, and FGF21 as indicators of disease severity in Charcot-Marie Tooth patients.Frontiers in neurology · 2024Article
- AAV-mediated editing of PMP22 rescues Charcot-Marie-Tooth disease type 1A features in patient-derived iPS Schwann cells.Communications medicine · 2023Article
- Trials for Slowly Progressive Neurogenetic Diseases Need Surrogate Endpoints.Annals of neurology · 2023Review
- Candidate imaging biomarkers for PMP22-related inherited neuropathies.Annals of clinical and translational neurology · 2022Article
- Accelerate Clinical Trials in Charcot-Marie-Tooth Disease (ACT-CMT): A Protocol to Address Clinical Trial Readiness in CMT1A.Frontiers in neurology · 2022Article
- Farnesol Ameliorates Demyelinating Phenotype in a Cellular and Animal Model of Charcot-Marie-Tooth Disease Type 1A.Current issues in molecular biology · 2021Article
- Mechanisms and Treatments in Demyelinating CMT.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2021Review
- Animal Models as a Tool to Design Therapeutical Strategies for CMT-like Hereditary Neuropathies.Brain sciences · 2021Review
11 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
importanceNo current medications improve neuropathy in subjects with Charcot-Marie-Tooth disease type 1A (CMT1A). Ascorbic acid (AA) treatment improved the neuropathy of a transgenic mouse model of CMT1A and is a potential therapy. A lower dosage (1.5 g/d) did not cause improvement in humans. It is unknown whether a higher dosage would prove more effective.
objectiveTo determine whether 4-g/d AA improves the neuropathy of subjects with CMT1A.
designA futility design to determine whether AA was unable to reduce worsening on the CMT Neuropathy Score (CMTNS) by at least 50% over a 2-year period relative to a natural history control group.
settingThree referral centers with peripheral nerve clinics (Wayne State University, Johns Hopkins University, and University of Rochester).
participantsOne hundred seventy-four subjects with CMT1A were assessed for eligibility; 48 did not meet eligibility criteria and 16 declined to participate. The remaining 110 subjects, aged 13 to 70 years, were randomly assigned in a double-masked fashion with 4:1 allocation to oral AA (87 subjects) or matching placebo (23 subjects). Sixty-nine subjects from the treatment group and 16 from the placebo group completed the study. Two subjects from the treatment group and 1 from the placebo group withdrew because of adverse effects.
interventionsOral AA (4 g/d) or matching placebo. MAIN OUTCOMES AND MEASURES: Change from baseline to year 2 in the CMTNS, a validated composite impairment score for CMT.
resultsThe mean 2-year change in the CMTNS was -0.21 for the AA group and -0.92 for the placebo group, both better than natural history (+1.33). This was well below 50% reduction of CMTNS worsening from natural history, so futility could not be declared (P > .99). CONCLUSIONS AND RELEVANCE: Both treated patients and those receiving placebo performed better than natural history. It seems unlikely that our results support undertaking a larger trial of 4-g/d AA treatment in subjects with CMT1A.
trial registrationclinicaltrials.gov Identifier: NCT00484510.
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What OpenQuestion holds
Registered trials
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.