Efficacy and Safety of Antioxidant Treatment With {alpha}-Lipoic Acid Over 4 Years in Diabetic Polyneuropathy: The NATHAN 1 Trial

Diabetes Care, 08/10/2011

Four–year treatment with α–lipoic acid (ALA) in mild–to–moderate diabetic distal symmetric sensorimotor polyneuropathy (DSPN) did not influence the primary composite end point but resulted in a clinically meaningful improvement and prevention of progression of neuropathic impairments and was well tolerated. Because the primary composite end point did not deteriorate significantly in placebo subjects, secondary prevention of its progression by ALA according to the trial design was not feasible.

Methods

  • In a multicenter randomized double–blind parallel–group trial, 460 diabetic patients with mild–to–moderate DSPN were randomly assigned to oral treatment with 600 mg ALA four times daily (n = 233) or placebo (n = 227) for 4 years.
  • Primary end point was a composite score (Neuropathy Impairment Score [NIS]–Lower Limbs [NIS–LL] and seven neurophysiologic tests).
  • Secondary outcome measures included NIS, NIS–LL, nerve conduction, and quantitative sensory tests (QSTs).

Results

  • Change in primary end point from baseline to 4 years showed no significant difference between treatment groups (P = 0.105).
  • Change from baseline was significantly better with ALA than placebo for NIS (P = 0.028), NIS–LL (P = 0.05), and NIS–LL muscular weakness subscore (P = 0.045).
  • More patients showed a clinically meaningful improvement and fewer showed progression of NIS (P = 0.013) and NIS–LL (P = 0.025) with ALA than with placebo.
  • Nerve conduction and QST results did not significantly worsen with placebo.
  • Global assessment of treatment tolerability and discontinuations due to lack of tolerability did not differ between the groups.
  • The rates of serious adverse events were higher on ALA (38.1%) than on placebo (28.0%).

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