Effect of ascorbic acid in patients with Charcot-Marie-Tooth disease type 1A: a multicentre, randomised, double-blind, placebo-controlled trial.
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.


RESULTS
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).


CONCLUSIONS
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.
Micallef
Joëlle
J
CIC-UPCET, CHU La Timone, AP-HM, UMR CNRS-Université de la Méditerranée 6193, Marseille, France.
Attarian
Shahram
S
Dubourg
Odile
O
Gonnaud
Pierre-Marie
PM
Hogrel
Jean-Yves
JY
Stojkovic
Tanya
T
Bernard
Rafaelle
R
Jouve
Elisabeth
E
Pitel
Severine
S
Vacherot
Francois
F
Remec
Jean-Francois
JF
Jomir
Laurent
L
Azabou
Eric
E
Al-Moussawi
Mahmoud
M
Lefebvre
Marie-Noelle
MN
Attolini
Laurence
L
Yaici
Sadek
S
Tanesse
Daniel
D
Fontes
Michel
M
Pouget
Jean
J
Blin
Olivier
O
D000328:Adult; D000975:Antioxidants / Q000009:adverse effects / Q000627:therapeutic use*; D001205:Ascorbic Acid / Q000009:adverse effects / Q000097:blood / Q000627:therapeutic use*; D002607:Charcot-Marie-Tooth Disease / Q000188:drug therapy* / Q000473:pathology / Q000523:psychology; D004311:Double-Blind Method; D005260:Female; D018737:Hand Strength / Q000502:physiology; D006801:Humans; D008297:Male; D008875:Middle Aged; D009068:Movement / Q000502:physiology; D053580:Muscle Strength; D011897:Random Allocation; D012677:Sensation / Q000502:physiology; D012959:Socioeconomic Factors; D016896:Treatment Outcome; D016138:Walking
D000975:Antioxidants; D001205:Ascorbic Acid