Oral high dose ascorbic acid treatment for one year in young CMT1A patients: a randomised, double-blind, placebo-controlled phase II trial

Camiel Verhamme, Rob J de Haan, Marinus Vermeulen, Frank Baas, Marianne de Visser, Ivo N van Schaik, Camiel Verhamme, Rob J de Haan, Marinus Vermeulen, Frank Baas, Marianne de Visser, Ivo N van Schaik

Abstract

Background: High dose oral ascorbic acid substantially improved myelination and locomotor function in a Charcot-Marie-Tooth type 1A mouse model. A phase II study was warranted to investigate whether high dose ascorbic acid also has such a substantial effect on myelination in Charcot-Marie-Tooth type 1A patients and whether this treatment is safe.

Methods: Patients below age 25 years were randomly assigned to receive placebo or ascorbic acid (one gram twice daily) in a double-blind fashion during one year. The primary outcome measure was the change over time in motor nerve conduction velocity of the median nerve. Secondary outcome measures included changes in minimal F response latencies, compound muscle action potential amplitude, muscle strength, sensory function, Charcot-Marie-Tooth neuropathy score, and disability.

Results: There were no significant differences between the six placebo-treated (median age 16 years, range 13 to 24) and the five ascorbic acid-treated (19, 14 to 24) patients in change in motor nerve conduction velocity of the median nerve (mean difference ascorbic acid as opposed to placebo treatment of 1.3 m/s, confidence interval -0.3 to 3.0 m/s, P = 0.11) or in change of any of the secondary outcome measures over time. One patient in the ascorbic acid group developed a skin rash, which led to discontinuation of the study medication.

Conclusion: Oral high dose ascorbic acid for one year did not improve myelination of the median nerve in young Charcot-Marie-Tooth type 1A patients. Treatment was relatively safe.

Trial registration: Current Controlled Trials ISRCTN56968278, ClinicalTrials.gov NCT00271635.

Figures

Figure 1
Figure 1
Flow diagram of the trial.
Figure 2
Figure 2
Motor nerve conduction velocities of the median nerve over time. Motor nerve conduction velocity (MNCV) of the median nerve (m/s) over time (months) in the placebo (A) and ascorbic acid (B) treated participants. Each connected symbol corresponds with an individual participant.

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