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Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy.

Abstract

OBJECTIVE

To evaluate the efficacy and safety of alpha-lipoic acid given intravenously, followed by oral treatment in type 2 diabetic patients with symptomatic polyneuropathy.

RESEARCH DESIGN AND METHODS

In a multicenter randomized double-blind placebo-controlled trial (Alpha-Lipoic Acid in Diabetic Neuropathy [ALADIN] III Study), 509 outpatients were randomly assigned to sequential treatment with 600 mg alpha-lipoic acid once daily intravenously for 3 weeks, followed by 600 mg alpha-lipoic acid three times a day orally for 6 months (A-A; n = 167); 600 mg alpha-lipoic acid once daily intravenously for 3 weeks, followed by placebo three times a day orally for 6 months (A-P; n = 174); and placebo once daily intravenously for 3 weeks, followed by placebo three times a day orally for 6 months (P-P; n = 168). Outcome measures included the Total Symptom Score (TSS) for neuropathic symptoms (pain, burning, paresthesias, and numbness) in the feet, and the Neuropathy Impairment Score (NIS). Data analysis was based on the intention to treat.

RESULTS

No significant differences between the groups were noted for the demographic variables and the nerve function parameters at baseline. The TSS in the feet decreased from baseline to day 19 (median [range]) by -3.7 (-12.6 to 5.0) points in the group given alpha-lipoic acid intravenously and by -3.0 (-12.3 to 8.0) points in the placebo group (P = 0.447), but the area under curve on a daily basis was significantly smaller in the active as compared with the placebo group (85.6 [0-219] vs. 95.9 [5.5-220]); P = 0.033). After 7 months, the changes in the TSS from baseline were not significantly different between the three groups studied, which could be due to increasing intercenter variability in the TSS during the trial. The NIS decreased after 19 days by -4.34+/-0.35 points (mean +/- SEM) in A-A and A-P and -3.49+/-0.58 points in P-P (P = 0.02 for alpha-lipoic acid versus placebo) and after 7 months by -5.82+/-0.73 points in A-A, -5.76+/-0.69 points in A-P, and -4.37+/-0.83 points in P-P (P = 0.09 for A-A vs. P-P). The rates of adverse events were not different between the groups throughout the study.

CONCLUSIONS

These findings indicate that a 3-week intravenous treatment with alpha-lipoic acid, followed by a 6-month oral treatment, had no effect on neuropathic symptoms distinguishable from placebo to a clinically meaningful degree, possibly due to increasing intercenter variability in symptom scoring during the study. However, this treatment was associated with a favorable effect on neuropathic deficits without causing significant adverse reactions. Long-term trials that focus on neuropathic deficits rather than symptoms as the primary criterion of efficacy are needed to see whether oral treatment with alpha-lipoic acid over several years may slow or reverse the progression of diabetic neuropathy.

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  • Authors+Show Affiliations

    ,

    Diabetes-Forschungsinstitut an der Heinrich-Heine-Universität, Düsseldorf, Germany. dan.ziegler@dfi.uni-duesseldorf.de

    , , , , , ,

    Source

    Diabetes care 22:8 1999 Aug pg 1296-301

    MeSH

    Administration, Oral
    Antioxidants
    Diabetes Mellitus, Type 2
    Diabetic Neuropathies
    Double-Blind Method
    Female
    Follow-Up Studies
    Humans
    Injections, Intravenous
    Male
    Middle Aged
    Thioctic Acid
    Treatment Outcome

    Pub Type(s)

    Clinical Trial
    Journal Article
    Multicenter Study
    Randomized Controlled Trial
    Research Support, Non-U.S. Gov't

    Language

    eng

    PubMed ID

    10480774

    Citation

    Ziegler, D, et al. "Treatment of Symptomatic Diabetic Polyneuropathy With the Antioxidant Alpha-lipoic Acid: a 7-month Multicenter Randomized Controlled Trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy." Diabetes Care, vol. 22, no. 8, 1999, pp. 1296-301.
    Ziegler D, Hanefeld M, Ruhnau KJ, et al. Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. Diabetes Care. 1999;22(8):1296-301.
    Ziegler, D., Hanefeld, M., Ruhnau, K. J., Hasche, H., Lobisch, M., Schütte, K., ... Malessa, R. (1999). Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. Diabetes Care, 22(8), pp. 1296-301.
    Ziegler D, et al. Treatment of Symptomatic Diabetic Polyneuropathy With the Antioxidant Alpha-lipoic Acid: a 7-month Multicenter Randomized Controlled Trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. Diabetes Care. 1999;22(8):1296-301. PubMed PMID: 10480774.
    * Article titles in AMA citation format should be in sentence-case
    TY - JOUR T1 - Treatment of symptomatic diabetic polyneuropathy with the antioxidant alpha-lipoic acid: a 7-month multicenter randomized controlled trial (ALADIN III Study). ALADIN III Study Group. Alpha-Lipoic Acid in Diabetic Neuropathy. AU - Ziegler,D, AU - Hanefeld,M, AU - Ruhnau,K J, AU - Hasche,H, AU - Lobisch,M, AU - Schütte,K, AU - Kerum,G, AU - Malessa,R, PY - 1999/9/10/pubmed PY - 1999/9/10/medline PY - 1999/9/10/entrez SP - 1296 EP - 301 JF - Diabetes care JO - Diabetes Care VL - 22 IS - 8 N2 - OBJECTIVE: To evaluate the efficacy and safety of alpha-lipoic acid given intravenously, followed by oral treatment in type 2 diabetic patients with symptomatic polyneuropathy. RESEARCH DESIGN AND METHODS: In a multicenter randomized double-blind placebo-controlled trial (Alpha-Lipoic Acid in Diabetic Neuropathy [ALADIN] III Study), 509 outpatients were randomly assigned to sequential treatment with 600 mg alpha-lipoic acid once daily intravenously for 3 weeks, followed by 600 mg alpha-lipoic acid three times a day orally for 6 months (A-A; n = 167); 600 mg alpha-lipoic acid once daily intravenously for 3 weeks, followed by placebo three times a day orally for 6 months (A-P; n = 174); and placebo once daily intravenously for 3 weeks, followed by placebo three times a day orally for 6 months (P-P; n = 168). Outcome measures included the Total Symptom Score (TSS) for neuropathic symptoms (pain, burning, paresthesias, and numbness) in the feet, and the Neuropathy Impairment Score (NIS). Data analysis was based on the intention to treat. RESULTS: No significant differences between the groups were noted for the demographic variables and the nerve function parameters at baseline. The TSS in the feet decreased from baseline to day 19 (median [range]) by -3.7 (-12.6 to 5.0) points in the group given alpha-lipoic acid intravenously and by -3.0 (-12.3 to 8.0) points in the placebo group (P = 0.447), but the area under curve on a daily basis was significantly smaller in the active as compared with the placebo group (85.6 [0-219] vs. 95.9 [5.5-220]); P = 0.033). After 7 months, the changes in the TSS from baseline were not significantly different between the three groups studied, which could be due to increasing intercenter variability in the TSS during the trial. The NIS decreased after 19 days by -4.34+/-0.35 points (mean +/- SEM) in A-A and A-P and -3.49+/-0.58 points in P-P (P = 0.02 for alpha-lipoic acid versus placebo) and after 7 months by -5.82+/-0.73 points in A-A, -5.76+/-0.69 points in A-P, and -4.37+/-0.83 points in P-P (P = 0.09 for A-A vs. P-P). The rates of adverse events were not different between the groups throughout the study. CONCLUSIONS: These findings indicate that a 3-week intravenous treatment with alpha-lipoic acid, followed by a 6-month oral treatment, had no effect on neuropathic symptoms distinguishable from placebo to a clinically meaningful degree, possibly due to increasing intercenter variability in symptom scoring during the study. However, this treatment was associated with a favorable effect on neuropathic deficits without causing significant adverse reactions. Long-term trials that focus on neuropathic deficits rather than symptoms as the primary criterion of efficacy are needed to see whether oral treatment with alpha-lipoic acid over several years may slow or reverse the progression of diabetic neuropathy. SN - 0149-5992 UR - https://www.unboundmedicine.com/medline/citation/10480774/Treatment_of_symptomatic_diabetic_polyneuropathy_with_the_antioxidant_alpha_lipoic_acid:_a_7_month_multicenter_randomized_controlled_trial__ALADIN_III_Study___ALADIN_III_Study_Group__Alpha_Lipoic_Acid_in_Diabetic_Neuropathy_ L2 - http://care.diabetesjournals.org/cgi/pmidlookup?view=long&pmid=10480774 DB - PRIME DP - Unbound Medicine ER -