CMT 1A: Effect of ascorbic acid in patients: a multicenter, randomised, double-b

October 13, 2009

Lancet Neurol. 2009 Oct 7. [Epub ahead of print]

Effect of ascorbic acid in patients with Charcot-Marie-Tooth disease type 1A: a

multicentre, randomised, double-blind, placebo-controlled trial.

Micallef J, Attarian S, Dubourg O, Gonnaud PM, Hogrel JY, Stojkovic T, Bernard

R, Jouve E, Pitel S, Vacherot F, Remec JF, Jomir L, Azabou E, Al-Moussawi M,

Lefebvre MN, Attolini L, Yaici S, Tanesse D, Fontes M, Pouget J, Blin O.

CIC-UPCET, CHU La Timone, AP-HM, UMR CNRS-Université de la Méditerranée 6193,

Marseille, France.

BACKGROUND: Charcot-Marie-Tooth disease type 1A (CMT1A) is a hereditary

peripheral neuropathy that affects roughly one in 5000 births. No specific

therapy currently exists for this degenerative disorder, which is characterised

by distal progressive muscle atrophy and sensory loss, although ascorbic acid

has been shown to reduce demyelination and improve muscle function in a

transgenic mouse model of CMT1A. We tested the safety and efficacy of ascorbic

acid in adults with CMT1A.

METHODS: This 12-month, randomised, double-blind, placebo-controlled study was

undertaken between September, 2005, and October, 2008. Patients diagnosed with

CMT1A according to clinical examination and confirmation by genotyping were

randomly assigned in a 1:1:1 ratio to receive 1 g ascorbic acid per day, 3 g

ascorbic acid per day, or placebo.

Treatment allocation was based on a computer-generated list of random numbers in

blocks of 12, with stratification according to study site and sex; all

investigators and participants were unaware of treatment allocation. The primary

outcome was the Charcot-Marie-Tooth disease neuropathy score (CMTNS) at 12

months.

Analysis was by intention to treat. This study is registered with the Orphanet

Database, number ORPHA60779.

FINDINGS: The median change in CMTNS from baseline to 12 months was 0.5 points

(95% CI -0.3 to 1.4) for the placebo group (n=62), 0.7 points (0.0 to 1.4) for

the 1 g ascorbic acid group (n=56), and -0.4 points (-1.2 to 0.4) for the 3 g

ascorbic acid group (n=61).

We did not find any significant difference in these changes between the groups

(p=0.14). The occurrence of adverse events did not differ between the groups

(p=0.74).

INTERPRETATION: Ascorbic acid at both doses was safe and well tolerated in

adults with CMT1A over 12 months. However, there were no significant differences

between the groups and the efficacy of ascorbic acid was not shown.

FUNDING: French Ministry of Health (National PHRC 2004) and Association

Française Contre les Myopathies.

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