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


CONCLUSIONS
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.


BACKGROUND
Current Controlled Trials ISRCTN56968278, ClinicalTrials.gov NCT00271635.
Verhamme
Camiel
C
Department of Neurology and Clinical Neurophysiology, Academic Medical Centre, University of Amsterdam, PO Box 22660, 1100 DD, Amsterdam, The Netherlands. c.verhamme@amc.uva.nl
de Haan
Rob J
RJ
Vermeulen
Marinus
M
Baas
Frank
F
de Visser
Marianne
M
van Schaik
Ivo N
IN
D000284:Administration, Oral; D000293:Adolescent; D001205:Ascorbic Acid / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D002607:Charcot-Marie-Tooth Disease / Q000188:drug therapy*; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008475:Median Nerve / Q000502:physiology; D053580:Muscle Strength / Q000187:drug effects; D009431:Neural Conduction / Q000502:physiology; D010919:Placebos / Q000008:administration & dosage; D012677:Sensation / Q000502:physiology; D012720:Severity of Illness Index; D016896:Treatment Outcome; D014815:Vitamins / Q000008:administration & dosage / Q000009:adverse effects* / Q000627:therapeutic use*; D055815:Young Adult
D010919:Placebos; D014815:Vitamins; D001205:Ascorbic Acid