title: Effect of ascorbic acid in patients with Charcot-Marie-Tooth disease type 1A: a multicentre, randomised, double-blind, placebo-controlled trial.
abstract: 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.
authors.affiliation: CIC-UPCET, CHU La Timone, AP-HM, UMR CNRS-Université de la Méditerranée 6193, Marseille, France.
authors.forename: Joëlle
authors.initials: J
authors.lastname: Micallef
authors.forename: Shahram
authors.initials: S
authors.lastname: Attarian
authors.forename: Odile
authors.initials: O
authors.lastname: Dubourg
authors.forename: Pierre-Marie
authors.initials: PM
authors.lastname: Gonnaud
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Hogrel
authors.forename: Tanya
authors.initials: T
authors.lastname: Stojkovic
authors.forename: Rafaelle
authors.initials: R
authors.lastname: Bernard
authors.forename: Elisabeth
authors.initials: E
authors.lastname: Jouve
authors.forename: Severine
authors.initials: S
authors.lastname: Pitel
authors.forename: Francois
authors.initials: F
authors.lastname: Vacherot
authors.forename: Jean-Francois
authors.initials: JF
authors.lastname: Remec
authors.forename: Laurent
authors.initials: L
authors.lastname: Jomir
authors.forename: Eric
authors.initials: E
authors.lastname: Azabou
authors.forename: Mahmoud
authors.initials: M
authors.lastname: Al-Moussawi
authors.forename: Marie-Noelle
authors.initials: MN
authors.lastname: Lefebvre
authors.forename: Laurence
authors.initials: L
authors.lastname: Attolini
authors.forename: Sadek
authors.initials: S
authors.lastname: Yaici
authors.forename: Daniel
authors.initials: D
authors.lastname: Tanesse
authors.forename: Michel
authors.initials: M
authors.lastname: Fontes
authors.forename: Jean
authors.initials: J
authors.lastname: Pouget
authors.forename: Olivier
authors.initials: O
authors.lastname: Blin
mesh_terms: 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
chemical_list: D000975:Antioxidants; D001205:Ascorbic Acid