Oral Treatment With α-Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy

Oral Treatment With α-Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy The SYDNEY 2 trial Dan Ziegler , MD, FRCPE 1 , Alexander Ametov , MD 2 , Alexey Barinov , MD 3 , Peter J. Dyck , MD 4 , Irina Gurieva , MD 5 , Phillip A. Low , MD 4 , Ullrich Munzel , PHD 6 , Nikolai Yakhno , MD 3 , Itamar Raz , MD 7 , Maria Novosadova , MD 5 , Joachim Maus , MD 6 and Rustem Samigullin , MD 6 1 German Diabetes Clinic, German Diabetes Center, Leibniz Institute at the Heinrich Heine University, Düsseldorf, Germany 2 Russian Medical Academy for Advanced Studies, Moscow, Russia 3 Neurology Clinic, Moscow Medical Academy, Moscow, Russia 4 Department of Neurology, Mayo Clinic, Rochester, Minnesota 5 Federal Center for Diabetic Foot, Moscow, Russia 6 MEDA Pharma, Bad Homburg, Germany 7 Hadassah University, Jerusalem, Israel Address correspondence and reprint requests to Prof. Dan Ziegler, MD, FRCPE, Deutsche Diabetes-Klinik, Deutsches Diabetes-Zentrum, Leibniz-Institut an der Heinrich-Heine-Universität, Auf’m Hennekamp 65, 40225 Düsseldorf, Germany. E-mail: dan.ziegler{at}ddz.uni-duesseldorf.de Abstract OBJECTIVE —The aim of this trial was to evaluate the effects of α-lipoic acid (ALA) on positive sensory symptoms and neuropathic deficits in diabetic patients with distal symmetric polyneuropathy (DSP). RESEARCH DESIGN AND METHODS —In this multicenter, randomized, double-blind, placebo-controlled trial, 181 diabetic patients in Russia and Israel received once-daily oral doses of 600 mg ( n = 45) (ALA600), 1,200 mg ( n = 47) (ALA1200), and 1,800 mg (ALA1800) of ALA ( n = 46) or placebo ( n = 43) for 5 weeks after a 1-week placebo run-in period. The primary outcome measure was the change from baseline of the Total Symptom Score (TSS), including stabbing pain, burning pain, paresthesia, and asleep numbness of the feet. Secondary end points included individual symptoms of TSS, Neuropathy Symptoms and Change (NSC) score, Neuropathy Impairment Score (NIS), and patients’ global assessment of efficacy. RESULTS —Mean TSS did not differ significantly at baseline among the treatment groups and on average decreased by 4.9 points (51%) in ALA600, 4.5 (48%) in ALA1200, and 4.7 (52%) in ALA1800 compared with 2.9 points (32%) in the placebo group (all P < 0.05 vs. placebo). The corresponding response rates (≥50% reduction in TSS) were 62, 50, 56, and 26%, respectively. Significant improvements favoring all three ALA groups were also noted for stabbing and burning pain, the NSC score, a