Ascorbic Acid Treatment in CMT1A Trial (AATIC)
Condition: Charcot-Marie-Tooth Disease; Hereditary Motor and Sensory Neuropathies
MeSH terms: Tooth Diseases; Charcot-Marie-Tooth Disease; Nerve Compression Syndromes; Hereditary Sensory and Motor Neuropathy
Study type: Interventional
Phase: Phase 2

Summary: 
      Charcot-Marie-Tooth type IA (CMT1A) is the most prevalent hereditary peripheral neuropathy.
      Demyelination of peripheral nerves is the hallmark of CMT1A. Ascorbic acid has been shown to
      have a favorable influence on myelination in in vitro studies and in a mouse model for CMT1A.
      We will study the efficacy and safety of ascorbic acid treatment in young patients with
      CMT1A.
    

Detailed description: 
      Charcot-Marie-Tooth type 1A (CMT1A), or hereditary motor and sensory neuropathy type Ia (HMSN
      Ia), is an autosomal dominant disease, most often caused by a 1.5 Mb duplication of
      chromosome 17, giving rise to three copies of the peripheral myelin protein 22 gene (PMP22).
      Mutations in this gene rarely cause CMT1A. It is a primarily demyelinating neuropathy, as has
      been shown in nerve conduction studies and in histopathological investigations. The
      conduction velocities of peripheral nerves are already slowed at the age of five years.
      Longitudinal data show that these conduction velocities do not change during life, indicating
      that the degree of demyelination is rather constant during life.

      CMT1A is characterized clinically by distal muscle weakness and wasting, legs more than arms,
      impaired distal sensation, and reduced or absent reflexes. Moreover, foot and hand
      deformities are often encountered. In childhood, disease progression has been shown. In
      adults, there are indications for disease progression, but properly conducted longitudinal
      studies are awaited. Cross-sectional studies show that disease severity in adults is
      variable: a group of CMT1A patients is asymptomatic (5-10%), whereas other patients are
      wheelchair dependent (5-10%), still most have the classical CMT phenotype. Therapy is
      symptomatic and aims at maintaining functional possibilities and learning compensation
      mechanisms. There is no medication available that stabilizes or improves the clinical signs
      and symptoms.

      Ascorbic acid is needed in in vitro studies for proper myelination of axons (in cultures
      containing serum). Recently, in a mouse model for CMT1A it has been shown that ascorbic acid
      improves the CMT1A phenotype. Mice (2-4 months old) treated with ascorbic acid once a week
      during three months showed an increase in the percentage of myelinating nerve fibers and
      showed better results in locomotor tests.

      In this phase 2 study we will study the efficacy and safety of ascorbic acid in young
      patients with CMT1A. We will investigate whether ascorbic acid induces remyelination by
      measuring the nerve conduction of a peripheral nerve during a one year study period. CMT1A
      patients aged 12 years or older may cooperate sufficiently in nerve conduction studies. We
      include young patients, as clinical signs and symptoms especially develop relatively early in
      life. These signs and symptoms are due to axonal dysfunction, secondary to the demyelination.
      This is why we will investigate additionally whether there is an effect of ascorbic acid
      treatment on axonal function, strength and disabilities.
    

Intervention name(s): Placebo; ascorbic acid
Intervention type(s): Drug; Drug
Intervention description(s): Placebo 4 capsules b.i.d. during 1 year; Ascorbic acid 1000 mg (4 capsules of 250 mg) b.i.d. during 1 year
Other intervention name(s): Vitamin C
Intervention MeSH terms: Ascorbic Acid
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Treatment
Keywords: Charcot-Marie-Tooth Disease; Hereditary Motor and Sensory Neuropathies; Ascorbic Acid; Vitamin C