Four years of treatment with alpha-lipoic acid for diabetic polyneuropathy failed to achieve the study’s primary endpoint but did yield some clinically meaningful improvements, an international team reports.…
Dr. Dan Ziegler, with Heinrich Heine University Hospital, Dusseldorf, Germany and colleagues reported that, the primary endpoint of the placebo-controlled NATHAN 1 trial was a composite of the Neuropathy Impairment Score-Lower Limbs (NIS-LL) and seven neurophysiologic tests.
That outcome was similar in the treatment and placebo groups. They attribute this null result largely to the lack of deterioration in nerve conduction and quantitative sensory tests (QST) in the placebo group.
However, the change in NIS-LL was significantly better with alpha-lipoic acid than placebo (p=0.05), as was the change in the muscular weakness subscore, according to the published report. The team had assigned 460 diabetic patients with mild-to-moderate polyneuropathy to receive oral alpha-lipoic acid 600 mg or matching placebo four times daily for four years.
Two intervention patients and one placebo patient discontinued because they couldn’t tolerate the treatment. Serious adverse events occurred in 38.1% of patients taking alpha-lipoic acid and in 28.0% of those on placebo.
Dr. Ziegler and colleagues 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.
“In conclusion,” they write, “four-year treatment with alpha-lipoic acid in mild-to-moderate DSPN was well tolerated and was associated with improvement of neuropathic impairments but not nerve conduction attributes.”
“The reasons for the disparity between the effects of alpha-lipoic acid on neuropathic deficits and nerve conduction or QST are not understood,” they add.
At a minimum, they note, “The designs of future trials in similar diabetic populations should anticipate a long-term stable neuropathic condition.”
Diabetes Care Aug.2011