NEW YORK (Reuters Health) – A 4-year placebo-controlled trial of alpha-lipoic acid to treat diabetes-related polyneuropathy produced no improvement in the study’s composite endpoint, but there were clinically meaningful improvements in impairment due to neuropathy.
Those findings are reported in Diabetes Care online July 20 by Dr. Dan Ziegler, with Heinrich Heine University Hospital, Dusseldorf, Germany and colleagues.
They note that effective treatment of distal symmetric sensorimotor polyneuropathy (DSPN) in diabetics remains a challenge, as the condition is not slowed by intensive diabetes therapy. Potentially disease-modifying therapeutic approaches have been developed, including treatment with antioxidants such as alpha-lipoic acid (ALA).
For the current study, the team assigned 460 diabetic patients with mild-to-moderate DSPN to receive oral ALA 600 mg or matching placebo four times daily for 4 years. The primary endpoint was a composite of the Neuropathy Impairment Score--Lower Limbs (NIS-LL) and seven neurophysiologic tests.
The change in primary endpoint from baseline to 4 years was not significantly different between treatment groups (p= 0.105), the researchers found. However, this null result was attributable largely to the lack of deterioration in nerve conduction and quantitative sensory tests (QST) in the placebo group. The change in NIS-LL was significantly better with ALA than placebo (p=0.05), as was the change in the muscular weakness subscore.
“The reasons for the disparity between the effects of ALA on neuropathic deficits and nerve conduction or QST are not understood,” the authors comment.
Two ALA patients and one placebo patient discontinued because of lack of tolerability. Serious adverse events occurred in 38.1% of patients in the ALA group and in 28.0% of those receiving placebo, Dr. Ziegler and colleagues report.
“In conclusion,” they write, “4-year treatment with ALA in mild-to-moderate DSPN was well tolerated and was associated with improvement of neuropathic impairments but not nerve conduction attributes.”
They advise, “The designs of future trials in similar diabetic populations should anticipate a long-term stable neuropathic condition.”
Efficacy and Safety of Antioxidant Treatment With ?-Lipoic Acid Over 4 Years in Diabetic Polyneuropathy
Diabetes Care 2011.