Oral treatment with alpha-lipoic acid improves symptomatic diabetic polyneuropathy: the SYDNEY 2 trial.
OBJECTIVE
The aim of this trial was to evaluate the effects of alpha-lipoic acid (ALA) on positive sensory symptoms and neuropathic deficits in diabetic patients with distal symmetric polyneuropathy (DSP).


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.
Ziegler
Dan
D
FRCPE, Deutsche Diabetes-Klinik, Deutsches Diabetes-Zentrum, Leibniz-Institut an der Heinrich-Heine-Universität, Auf'm Hennekamp 65, 40225 Düsseldorf, Germany. dan.ziegler@ddz.uni-duesseldorf.de
Ametov
Alexander
A
Barinov
Alexey
A
Dyck
Peter J
PJ
Gurieva
Irina
I
Low
Phillip A
PA
Munzel
Ullrich
U
Yakhno
Nikolai
N
Raz
Itamar
I
Novosadova
Maria
M
Maus
Joachim
J
Samigullin
Rustem
R
D000284:Administration, Oral; D000368:Aged; D003929:Diabetic Neuropathies / Q000188:drug therapy*; D005260:Female; D005528:Foot; D006801:Humans; D008297:Male; D008875:Middle Aged; D010146:Pain / Q000188:drug therapy; D010292:Paresthesia / Q000188:drug therapy; D008063:Thioctic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome; D014803:Vitamin B Complex / Q000008:administration & dosage* / Q000009:adverse effects
D014803:Vitamin B Complex; D008063:Thioctic Acid