Clinical Trial: Ascorbic Acid Treatment in CMT1A Trial (AATIC)

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

Official Title: Phase 2 Study of Ascorbic Acid Treatment in Charcot-Marie-Tooth Type 1A

Brief 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 Summary:

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
Sponsor: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Current Primary Outcome: Change in motor nerve conduction velocity of the median nerve after 1 year [ Time Frame: 1 year ]

Original Primary Outcome: Change in motor nerve conduction velocity of the median nerve after 1 year

Current Secondary Outcome:

  • Change in minimal F response latency of the median nerve after 1 year [ Time Frame: 1 year ]
  • Changes in compound muscle action potential amplitude and area after 1 year [ Time Frame: 1 year ]
  • Change in motor unit number estimation of the abductor pollicis brevis muscle after 1 year [ Time Frame: 1 year ]
  • Changes in handgrip strength, strength of armflexors, foot dorsiflexors, knee extensors and hip flexors after 1 year [ Time Frame: 1 year ]
  • Change in overall disability sum score after 1 year [ Time Frame: 1 year ]
  • Change in AMC Linear Disability Scale score after 1 year [ Time Frame: 1 year ]
  • Evaluation of serum ascorbic acid concentrations during 1 year [ Time Frame: 1 year ]
  • Evaluation of side effects during 1 year [ Time Frame: 1 year ]


Original Secondary Outcome:

  • Change in minimal F response latency of the median nerve after 1 year
  • Changes in compound muscle action potential amplitude and area after 1 year
  • Change in motor unit number estimation of the abductor pollicis brevis muscle after 1 year
  • Changes in handgrip strength, strength of armflexors, foot dorsiflexors, knee extensors and hip flexors after 1 year
  • Change in overall disability sum score after 1 year
  • Change in AMC Linear Disability Scale score after 1 year
  • Evaluation of serum ascorbic acid concentrations during 1 year
  • Evaluation of side effects during 1 year


Information By: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA)

Dates:
Date Received: January 3, 2006
Date Started: January 2006
Date Completion:
Last Updated: July 2, 2008
Last Verified: July 2008