Open Access Research article

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

Camiel Verhamme1*, Rob J de Haan2, Marinus Vermeulen1, Frank Baas1, Marianne de Visser1 and Ivo N van Schaik1

Author Affiliations

1 Department of Neurology and Clinical Neurophysiology, Academic Medical Centre, University of Amsterdam, PO Box 22660, 1100 DD, Amsterdam, The Netherlands

2 Department of Clinical Epidemiology and Biostatistics, Academic Medical Centre, University of Amsterdam, PO Box 22660, 1100 DD, Amsterdam, The Netherlands

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BMC Medicine 2009, 7:70  doi:10.1186/1741-7015-7-70

Published: 12 November 2009

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.