Oral Treatment With α-Lipoic Acid Improves Symptomatic Diabetic Polyneuropathy

The SYDNEY 2 trial

  1. Dan Ziegler, MD, FRCPE1,
  2. Alexander Ametov, MD2,
  3. Alexey Barinov, MD3,
  4. Peter J. Dyck, MD4,
  5. Irina Gurieva, MD5,
  6. Phillip A. Low, MD4,
  7. Ullrich Munzel, PHD6,
  8. Nikolai Yakhno, MD3,
  9. Itamar Raz, MD7,
  10. Maria Novosadova, MD5,
  11. Joachim Maus, MD6 and
  12. Rustem Samigullin, MD6
  1. 1German Diabetes Clinic, German Diabetes Center, Leibniz Institute at the Heinrich Heine University, Düsseldorf, Germany
  2. 2Russian Medical Academy for Advanced Studies, Moscow, Russia
  3. 3Neurology Clinic, Moscow Medical Academy, Moscow, Russia
  4. 4Department of Neurology, Mayo Clinic, Rochester, Minnesota
  5. 5Federal Center for Diabetic Foot, Moscow, Russia
  6. 6MEDA Pharma, Bad Homburg, Germany
  7. 7Hadassah University, Jerusalem, Israel
  1. 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, and the patients’ global assessment of efficacy. The NIS was numerically reduced. Safety analysis showed a dose-dependent increase in nausea, vomiting, and vertigo.

CONCLUSIONS—Oral treatment with ALA for 5 weeks improved neuropathic symptoms and deficits in patients with DSP. An oral dose of 600 mg once daily appears to provide the optimum risk-to-benefit ratio.

Footnotes

  • D. Z., A.A., A.B., P.J.D., I.G., P.A.L., N.Y., I.R., and M.N. received honoraria for speaking activities and research grants from MEDA.

    A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.

    The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C Section 1734 solely to indicate this fact.

    • Accepted July 26, 2006.
    • Received June 12, 2006.
| Table of Contents