The sensory symptoms of diabetic polyneuropathy are improved with alpha-lipoic acid: the SYDNEY trial.
OBJECTIVE
Because alpha-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.


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.
Ametov
Alexander S
AS
Russian Medical Academy for Advanced Studies, Moscow, Russia.
Barinov
Alexei
A
Dyck
Peter J
PJ
Hermann
Robert
R
Kozlova
Natalia
N
Litchy
William J
WJ
Low
Phillip A
PA
Nehrdich
Detlef
D
Novosadova
Maria
M
O'Brien
Peter C
PC
Reljanovic
Miroslav
M
Samigullin
Rustem
R
Schuette
Klemens
K
Strokov
Igor
I
Tritschler
Hans J
HJ
Wessel
Klaus
K
Yakhno
Nikolai
N
Ziegler
Dan
D
D000368:Aged; D000975:Antioxidants / Q000008:administration & dosage* / Q000009:adverse effects; D003929:Diabetic Neuropathies / Q000175:diagnosis / Q000188:drug therapy* / Q000503:physiopathology; D005260:Female; D006801:Humans; D007275:Injections, Intravenous; D008297:Male; D008875:Middle Aged; D009431:Neural Conduction; D009475:Neurons, Afferent / Q000502:physiology; D008063:Thioctic Acid / Q000008:administration & dosage* / Q000009:adverse effects; D016896:Treatment Outcome
D000975:Antioxidants; D008063:Thioctic Acid