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JAMA Neurol. 2013 Aug;70(8):981-7. doi: 10.1001/jamaneurol.2013.3178.

High-dosage ascorbic acid treatment in Charcot-Marie-Tooth disease type 1A: results of a randomized, double-masked, controlled trial.

Author information

1
Department of Neurology, Wayne State University, Detroit, Michigan, USA.

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.

TRIAL REGISTRATION:

clinicaltrials.gov Identifier: NCT00484510.

PMID:
23797954
PMCID:
PMC3752369
DOI:
10.1001/jamaneurol.2013.3178
[Indexed for MEDLINE]
Free PMC Article
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