The Sensory Symptoms of Diabetic Polyneuropathy Are Improved With α-Lipoic Acid
The SYDNEY Trial
- The SYDNEY Trial Authors, for the SYDNEY Trial Study Group:,
- Alexander S. Ametov, MD1,
- Alexei Barinov, MD2,
- Peter J. Dyck, MD3,
- Robert Hermann, MD4,
- Natalia Kozlova, MD5,
- William J. Litchy, MD6,
- Phillip A. Low, MD3,
- Detlef Nehrdich, DIPL STAT4,
- Maria Novosadova, MD5,
- Peter C. O’Brien, PHD3,
- Miroslav Reljanovic, MD6,
- Rustem Samigullin, MD4,
- Klemens Schuette, BSC3,
- Igor Strokov, MD1,
- Hans J. Tritschler, PHD4,
- Klaus Wessel, PHD4,
- Nikolai Yakhno, MD2 and
- Dan Ziegler, MD7
- 1Russian Medical Academy for Advanced Studies, Moscow, Russia
- 2Neurology Clinic, Moscow Medical Academy, Russia
- 3Mayo Clinic, Rochester, Minnesota
- 4Viatris GmbH, Frankfurt, Germany
- 5Health Partners Medical Group, Minneapolis, Minnesota
- 6Ergomed, Zagreb, Croatia
- 7German Diabetes Research Institute, University of Düsseldorf, Germany
OBJECTIVE— Because α-lipoic acid (ALA), a potent antioxidant, prevents or improves nerve conduction attributes, endoneurial blood flow, and nerve (Na(+) K(+) ATPase activity in experimental diabetes and in humans and may improve positive neuropathic sensory symptoms, in this report we further assess the safety and efficacy of ALA on the Total Symptom Score (TSS), a measure of positive neuropathic sensory symptoms.
RESEARCH DESIGN AND METHODS— Metabolically stable diabetic patients with symptomatic (stage 2) diabetic sensorimotor polyneuropathy (DSPN) were randomized to a parallel, double-blind study of ALA (600 mg) (n = 60) or placebo (n = 60) infused daily intravenously for 5 days/week for 14 treatments. The primary end point was change of the sum score of daily assessments of severity and duration of TSS. Secondary end points were sum scores of neuropathy signs (NIS), symptoms (NSC), attributes of nerve conduction, quantitative sensation tests (QSTs), and an autonomic test.
RESULTS— At randomization, the groups were not significantly different by the criteria of metabolic control or neuropathic end points. After 14 treatments, the TSS of the ALA group had improved from baseline by an average of 5.7 points and the placebo group by an average of 1.8 points (P < 0.001). Statistically significant improvement from baseline of the ALA, as compared with the placebo group, was also found for each item of the TSS (lancinating and burning pain, asleep numbness and prickling), NIS, one attribute of nerve conduction, and global assessment of efficacy.
CONCLUSIONS— Intravenous racemic ALA, a potent antioxidant, rapidly and to a significant and meaningful degree, improved such positive neuropathic sensory symptoms as pain and several other neuropathic end points. This improvement of symptoms was attributed to improved nerve pathophysiology, not to increased nerve fiber degeneration. Because of its safety profile and its effect on positive neuropathic sensory symptoms and other neuropathic end points, this drug appears to be a useful ancillary treatment for the symptoms of diabetic polyneuropathy.
- ALA, α-lipoic acid
- DSPN, diabetic sensorimotor polyneuropathy
- HP-DB, heart pulse deep breathing
- ITT, intent-to-treat
- NIS, neuropathy impairment score
- NIS(LL), NIS of lower limbs
- NSC, neuropathy symptoms and change
- NSC(LL), neuropathy symptoms and change of lower limbs
- PP, per protocol
- QST, quantitative sensation test
- TSS, Total Symptom Score
This report was prepared by P.J.D.
Address correspondence and reprint requests to Peter J. Dyck, MD, Mayo Clinic, 200 First St. SW, Rochester, MN 55905. E-mail:.
Received for publication 1 August 2002 and accepted in revised form 10 December 2002.
P.J.D., W.J.L., P.A.L., and D.Z. have received honoraria from Vitaris GmbH and/or have served on an advisory panel for Vitaris GmbH, the manufacturer of α-lipoic acid.
A table elsewhere in this issue shows conventional and Système International (SI) units and conversion factors for many substances.
- DIABETES CARE