Effect of high-dose creatine therapy on symptoms of exercise intolerance in McArdle disease: double-blind, placebo-controlled crossover study.
BACKGROUND
In a recent study, we showed that administration of low-dose creatine (Cr) (60 mg/kg daily) improved work capacity in patients with McArdle disease.


OBJECTIVE
To assess the efficacy of high-dose Cr therapy in McArdle disease.


METHODS
Randomized, double-blind, placebo-controlled crossover study.


METHODS
Nineteen patients with McArdle disease.


METHODS
Treatment with Cr, 150 mg/kg daily. Each treatment phase with Cr or placebo lasted 5 weeks.


METHODS
The patient's daily rating of symptoms of exercise intolerance. At the end of each treatment phase, serum creatine and serum creatine kinase levels, phosphorus 31 magnetic resonance spectroscopy, and surface electromyograms were assessed.


RESULTS
Clinical end points revealed increases in the intensity of exercise-induced pain in working muscles (mean treatment-induced difference [d], 0.30 in log(score); 95% confidence interval [CI], 0.05-0.55; P =.02), the limitation of daily activities (d, 0.59; 95% CI, 0.22-0.97;P =.005), and body mass index (d, 0.33 kg/m2, 95% CI, 0.10-0.56 kg/m2; P =.008) with Cr use. Surface electromyograms revealed a smaller increase in the electromyographic amplitude over time during muscle contraction with Cr use (d, -13.52%/min; 95% CI, -23.71%/min to -3.34%/min; P =.01). There were no significant changes in phosphorus 31 magnetic resonance spectroscopy variables.


CONCLUSIONS
Administration of high-dose Cr worsened the main clinical symptoms of exercise intolerance in McArdle disease. These neurologic adverse effects represent a major dose-limiting factor in Cr therapy for McArdle disease. Taken together with results of a previous study, the indication for symptomatic therapy with Cr needs to be clarified. An effective Cr dosage without adverse effects may be between 60 and 150 mg/kg daily.
Vorgerd
Matthias
M
Department of Neurology, Ruhr-University Bochum, Kliniken Bergmannsheil, Bürkle-de-la-Camp-Platz 1, 44789 Bochum, Germany. matthias.vorgerd@ruhr-uni-bochum.de
Zange
Jochen
J
Kley
Rudolf
R
Grehl
T
T
Hüsing
Anika
A
Jäger
Matthias
M
Müller
Klaus
K
Schröder
Rolf
R
Mortier
Wilhelm
W
Fabian
Klaus
K
Malin
Jean-Pierre
JP
Luttmann
Alwin
A
D000293:Adolescent; D000328:Adult; D002648:Child; D003401:Creatine / Q000008:administration & dosage* / Q000009:adverse effects*; D018592:Cross-Over Studies; D004311:Double-Blind Method; D004576:Electromyography; D015444:Exercise; D005260:Female; D006012:Glycogen Storage Disease Type V / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008875:Middle Aged; D018763:Muscle Fatigue / Q000187:drug effects; D010759:Phosphorus Isotopes; D017211:Treatment Failure
D010759:Phosphorus Isotopes; D003401:Creatine