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Double-blind, Placebo-Controlled Crossover Study

Matthias Vorgerd, MD; Jochen Zange, PhD; Rudolf Kley; T. Grehl, MD; Anika Hüsing; Matthias Jäger, PhD; Klaus Müller, MD; Rolf Schröder, MD; Wilhelm Mortier, MD; Klaus Fabian, PhD; Jean-Pierre Malin, MD; Alwin Luttmann, PhD

Arch Neurol. 2002;59:97-101.

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.

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

Patients  Nineteen patients with McArdle disease.

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

Main Outcome Measures  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.

From the Departments of Neurology (Drs Vorgerd, Grehl, and Malin and Mr Kley), Medical Informatics, Biometrics, and Epidemiology (Ms Hüsing), and Pediatrics (Dr Mortier), Ruhr-University Bochum, Bochum; the German Aerospace Center, Cologne (Drs Zange and Müller); the Institute of Occupational Physiology, University of Dortmund, Dortmund (Drs Jäger and Luttmann); the Department of Neurology, University of Bonn, Bonn (Dr Schröder); and the Institute of Sports Medicine, University of Dresden, Dresden (Dr Fabian), Germany.

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