Journal article
High-Dosage Ascorbic Acid Treatment in Charcot-Marie-Tooth Disease Type 1A: Results of a Randomized, Double-Masked, Controlled Trial
JAMA neurology, Vol.70(8), pp.981-987
08/01/2013
DOI: 10.1001/jamaneurol.2013.3178
PMCID: PMC3752369
PMID: 23797954
Abstract
Importance: No 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.
Objective: To determine whether 4-g/d AA improves the neuropathy of subjects with CMT1A.
Design: A 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.
Setting: Three referral centers with peripheral nerve clinics (Wayne State University, Johns Hopkins University, and University of Rochester).
Participants: One 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.
Interventions: Oral 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.
Results: The 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.
Details
- Title: Subtitle
- High-Dosage Ascorbic Acid Treatment in Charcot-Marie-Tooth Disease Type 1A: Results of a Randomized, Double-Masked, Controlled Trial
- Creators
- Richard A Lewis - Department of Neurology, Wayne State University, Detroit, MichiganMichael P McDermott - Department of Biostatistics and Computational Biology, University of Rochester, Rochester, New York. Department of Neurology, University of Rochester, Rochester, New YorkDavid N Herrmann - Department of Neurology, University of Rochester, Rochester, New YorkAhmet Hoke - Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MarylandLora L Clawson - Department of Neurology, Johns Hopkins School of Medicine, Baltimore, MarylandCarly Siskind - Department of Neurology, Wayne State University, Detroit, MichiganShawna M. E Feely - Department of Neurology, Wayne State University, Detroit, MichiganLindsey J Miller - Department of Neurology, Wayne State University, Detroit, MichiganRichard J Barohn - Department of Neurology, University of Kansas, Kansas CityPatricia Smith - Department of Neurology, University of Rochester, Rochester, New YorkElizabeth Luebbe - Department of Neurology, University of Rochester, Rochester, New YorkXingyao Wu - Department of Neurology, Wayne State University, Detroit, MichiganMichael E Shy - Department of Neurology, Wayne State University, Detroit, Michigan
- Resource Type
- Journal article
- Publication Details
- JAMA neurology, Vol.70(8), pp.981-987
- DOI
- 10.1001/jamaneurol.2013.3178
- PMID
- 23797954
- PMCID
- PMC3752369
- ISSN
- 2168-6149
- eISSN
- 2168-6157
- Grant note
- U54 NS065712 || NS / National Institute of Neurological Disorders and Stroke : NINDS
- Language
- English
- Date published
- 08/01/2013
- Academic Unit
- Neurology; Molecular Physiology and Biophysics; Stead Family Department of Pediatrics; Iowa Neuroscience Institute
- Record Identifier
- 9984020747102771