MULTICENTRE, RANDOMISED. DOUBLE BLIND, PLACEBO CONTROLLED TRIAL OF ASCORBIC ACID TREATMENT IN CHARCOT-MARIE-TOOTH DISEASE TYPE 1A (CMT1A)

Charcot-Marie-Tooth disease (CMT) is the most frequent neuromuscular hereditary disorder, although it is classified among the so-called rare diseases. There is no effective treatment for such neuropathies. CMT1A is the most frequent subtype, and is due to the excessive expression of the peripheral myelin protein PMP22. Transgenic animal models can reproduce the human disease. A recent study showed that CMT1A mice treated with ascorbic acid (AA, the common Vitamin C) have much less severe neuropathy as compared to untreated controls, as shown by clinical and histologic findings. Some clinical parameters even improved during treatment. Further experiments confirmed that AA reduces PMP22 expression. A clinical trial evaluating the efficacy of AA treatment in CMT1A patients is feasible and warranted, as Vitamin C is devoid of significant side effects and easily available. The efficacy of ascorbic acid treatment will be assessed through a multicentric, randomised, double blind, placebo-controlled trial. Two hundreds patients will be recruited and randomly assigned to AA treatment (1 gram daily) or to placebo, for two years. Clinical and electrophysiological evaluations (employing internationally validated impairment, disability, and quality of life scales) will be performed before treatment and after 6-12-18-24 months. Skin biopsy to determine skin sensory fibre density will be performed in a subgroup of patients at the beginning and at the end of treatment. Efficacy of therapy will be assessed by comparing outcome measures in AA and placebo treated groups. The study will allow a definite statement on efficacy of a low-cost therapy for one of the most frequent inherited neuromuscular disorder; furthermore, an improvement in outcome assessment, homogeneously performed in a co-ordinated network of centres, for future trials will be obtained.