Treatment of diabetic polyneuropathy with the antioxidant thioctic acid (alpha-lipoic acid): A two year multicenter randomized double-blind placebo-controlled trial (ALADIN II)

Short-term trials with the antioxidant thioctic acid (TA) appear to improve neuropathic symptoms in diabetic patients, but the long-term response rema ins to be established. Therefore, Type 1 and Type 2 diabetic patients with symptomatic polyneuropathy were randomly assigned to three treatment regime ns: (1) 2 x 600 mg of TA (TA 1200), (2) 600 mg of TA plus placebo (PLA) (TA 600) or (3) placebo and placebo (PLA). A trometamol salt solution of TA of 1200 or 600 mg or PLA was intravenously administered once daily for five c onsecutive days before enrolling the patients in the oral treatment phase. The study was prospective, PLA-controlled, randomized, double-blind and con ducted for two years. Severity of diabetic neuropathy was assessed by the N europathy Disability Score (NDS) and electrophysiological attributes of the sural (sensory nerve conduction velocity (SNCV), sensory nerve action pote ntial (SNAP)) and the tibial (motor nerve conduction velocity (MNCV), motor nerve distal latency (MNDL)) nerve. Statistical analysis was performed aft er independent reviewers excluded all patients with highly variable data al lowing a final analysis of 65 patients (TA 1200: n = 18, TA 600: n = 27; PL A: n = 20). At baseline no significant differences were noted between the g roups regarding the demographic variables and peripheral nerve function par ameters for these 65 patients. Statistically significant changes after 24 m onths between TA and PLA were observed (mean +/- SD) for sural SNCV: +3.8 /- 4.2 m/s in TA 1200, +3.0 +/- 3.0 m/s in TA 600, -0.1 +/- 4.8 m/s in PLA (p < 0.05 for TA 1200 and TA 600 vs. PLA); sural SNAP: +0.6 +/- 2.5 mu V in TA 1200, +0.3 +/- 1.4 mu V in TA 600, -0.7 +/- 1.5 mu Vin PLA (p = 0.076 f or TA 1200 vs. PLA and p < 0.05 for TA 600 vs. PLA), and in tibial MNCV: +1 .2 +/- 3.8 m/s in TA 1200, -0.3 +/- 5.2 m/s in TA 600, -1.5 +/- 2.9 m/s in PLA (p < 0.05 for TA 1200 vs. PLA). No significant differences between the groups after 24 months were noted regarding the tibial MNDL and the NDS. We conclude that in a subgroup of patients after exclusion of patients with e xcessive test variability throughout the trial, TA appeared to have a benef icial effect on several attributes of nerve conduction.