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Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial.
Diabetes Care 2011; 34(9):2054-60DC

Abstract

OBJECTIVE

To evaluate the efficacy and safety of α-lipoic acid (ALA) over 4 years in mild-to-moderate diabetic distal symmetric sensorimotor polyneuropathy (DSPN). RESEARCH DESIGN AND 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 once 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%).

CONCLUSIONS

Four-year treatment with ALA in mild-to-moderate 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-treated subjects, secondary prevention of its progression by ALA according to the trial design was not feasible.

Authors+Show Affiliations

Institute for Clinical Diabetology, German Diabetes Center at the Heinrich Heine University, Germany. dan.ziegler@ddz.uni-duesseldorf.deNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Randomized Controlled Trial

Language

eng

PubMed ID

21775755

Citation

Ziegler, Dan, et al. "Efficacy and Safety of Antioxidant Treatment With Α-lipoic Acid Over 4 Years in Diabetic Polyneuropathy: the NATHAN 1 Trial." Diabetes Care, vol. 34, no. 9, 2011, pp. 2054-60.
Ziegler D, Low PA, Litchy WJ, et al. Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care. 2011;34(9):2054-60.
Ziegler, D., Low, P. A., Litchy, W. J., Boulton, A. J., Vinik, A. I., Freeman, R., ... Dyck, P. J. (2011). Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. Diabetes Care, 34(9), pp. 2054-60. doi:10.2337/dc11-0503.
Ziegler D, et al. Efficacy and Safety of Antioxidant Treatment With Α-lipoic Acid Over 4 Years in Diabetic Polyneuropathy: the NATHAN 1 Trial. Diabetes Care. 2011;34(9):2054-60. PubMed PMID: 21775755.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Efficacy and safety of antioxidant treatment with α-lipoic acid over 4 years in diabetic polyneuropathy: the NATHAN 1 trial. AU - Ziegler,Dan, AU - Low,Phillip A, AU - Litchy,William J, AU - Boulton,Andrew J M, AU - Vinik,Aaron I, AU - Freeman,Roy, AU - Samigullin,Rustem, AU - Tritschler,Hans, AU - Munzel,Ullrich, AU - Maus,Joachim, AU - Schütte,Klemens, AU - Dyck,Peter J, Y1 - 2011/07/20/ PY - 2011/7/22/entrez PY - 2011/7/22/pubmed PY - 2012/5/12/medline SP - 2054 EP - 60 JF - Diabetes care JO - Diabetes Care VL - 34 IS - 9 N2 - OBJECTIVE: To evaluate the efficacy and safety of α-lipoic acid (ALA) over 4 years in mild-to-moderate diabetic distal symmetric sensorimotor polyneuropathy (DSPN). RESEARCH DESIGN AND 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 once 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%). CONCLUSIONS: Four-year treatment with ALA in mild-to-moderate 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-treated subjects, secondary prevention of its progression by ALA according to the trial design was not feasible. SN - 1935-5548 UR - https://www.unboundmedicine.com/medline/citation/21775755/full_citation L2 - http://care.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=21775755 DB - PRIME DP - Unbound Medicine ER -