HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Erratum (v25,p413) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Hotta, N. Articles by Sakamoto, N. Search for Related Content PubMed PubMed Citation Articles by Hotta, N. Articles by Sakamoto, N. Social Bookmarking                What's this?

Clinical Efficacy of Fidarestat, a Novel Aldose Reductase Inhibitor, for Diabetic Peripheral Neuropathy

A 52-week multicenter placebo-controlled double-blind parallel group study

¹ Third Department of Internal Medicine, Nagoya University School of Medicine, Nagoya
² Third Department of Internal Medicine, School of Medicine, Tohoku University, Sendai
³ Department of Internal Medicine, Tokyo Saiseikai Central Hospital, Tokyo
⁴ Shiga University of Medical Science, Ohtsu
⁵ Third Department of Medicine, Shiga University of Medical Science, Ohtsu
⁶ Yamaguchi Rosai Hospital, Ube
⁷ Tokai Central Hospital, Kagamigahara
⁸ Nagoya University College of Medical Technology, Nagoya
⁹ Neurophysiology Section, Department of Examination, Nagoya University, Nagoya
¹⁰ Fourth Department of Internal Medicine, Saitama Medical School, Saitama
¹¹ Chubu Rosai Hospital, Nagoya, Japan

OBJECTIVE—The purpose of this study was to evaluate the efficacy of fidarestat, a novel aldose reductase (AR) inhibitor, in a double-blind placebo controlled study in patients with type 1 and type 2 diabetes and associated peripheral neuropathy.

RESEARCH DESIGN AND METHODS—A total of 279 patients with diabetic neuropathy were treated with placebo or fidarestat at a daily dose of 1 mg for 52 weeks. The efficacy evaluation was based on change in electrophysiological measurements of median and tibial motor nerve conduction velocity, F-wave minimum latency, F-wave conduction velocity (FCV), and median sensory nerve conduction velocity (forearm and distal), as well as an assessment of subjective symptoms.

RESULTS—Over the course of the study, five of the eight electrophysiological measures assessed showed significant improvement from baseline in the fidarestat-treated group, whereas no measure showed significant deterioration. In contrast, in the placebo group, no electrophysiological measure was improved, and one measure significantly deteriorated (i.e., median nerve FCV). At the study conclusion, the fidarestat-treated group was significantly improved compared with the placebo group in two electrophysiological measures (i.e., median nerve FCV and minimal latency). Subjective symptoms (including numbness, spontaneous pain, sensation of rigidity, paresthesia in the sole upon walking, heaviness in the foot, and hypesthesia) benefited from fidarestat treatment, and all were significantly improved in the treated versus placebo group at the study conclusion. At the dose used, fidarestat was well tolerated, with an adverse event profile that did not significantly differ from that seen in the placebo group.

CONCLUSIONS—The effects of fidarestat-treatment on nerve conduction and the subjective symptoms of diabetic neuropathy provide evidence that this treatment alters the progression of diabetic neuropathy.

Abbreviations: AR, aldose reductase • FCV, F-wave conduction velocity • MNCV, motor nerve conduction velocity • SNCV, sensory nerve conduction velocity

CiteULike    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				G. J. Ryan New pharmacologic approachesto treating diabetic retinopathy Am. J. Health Syst. Pharm., September 1, 2007; 64(17_Supplement_12): S15 - S21. [Abstract] [Full Text] [PDF]

				V. R. Drel, N. Mashtalir, O. Ilnytska, J. Shin, F. Li, V. V. Lyzogubov, and I. G. Obrosova The Leptin-Deficient (ob/ob) Mouse: A New Animal Model of Peripheral Neuropathy of Type 2 Diabetes and Obesity Diabetes, December 1, 2006; 55(12): 3335 - 3343. [Abstract] [Full Text] [PDF]

				N. Hotta, Y. Akanuma, R. Kawamori, K. Matsuoka, Y. Oka, M. Shichiri, T. Toyota, M. Nakashima, I. Yoshimura, N. Sakamoto, et al. Long-Term Clinical Effects of Epalrestat, an Aldose Reductase Inhibitor, on Diabetic Peripheral Neuropathy: The 3-year, multicenter, comparative Aldose Reductase Inhibitor-Diabetes Complications Trial Diabetes Care, July 1, 2006; 29(7): 1538 - 1544. [Abstract] [Full Text] [PDF]

				W. Sun, C. Gerhardinger, Z. Dagher, T. Hoehn, and M. Lorenzi Aspirin at Low-Intermediate Concentrations Protects Retinal Vessels in Experimental Diabetic Retinopathy Through Non-Platelet-Mediated Effects Diabetes, December 1, 2005; 54(12): 3418 - 3426. [Abstract] [Full Text] [PDF]

				F. Li, V. R. Drel, C. Szabo, M. J. Stevens, and I. G. Obrosova Low-Dose Poly(ADP-Ribose) Polymerase Inhibitor-Containing Combination Therapies Reverse Early Peripheral Diabetic Neuropathy Diabetes, May 1, 2005; 54(5): 1514 - 1522. [Abstract] [Full Text] [PDF]

				I. G. Obrosova, P. Pacher, C. Szabo, Z. Zsengeller, H. Hirooka, M. J. Stevens, and M. A. Yorek Aldose Reductase Inhibition Counteracts Oxidative-Nitrosative Stress and Poly(ADP-Ribose) Polymerase Activation in Tissue Sites for Diabetes Complications Diabetes, January 1, 2005; 54(1): 234 - 242. [Abstract] [Full Text] [PDF]

				K. Uehara, S.-I. Yamagishi, S. Otsuki, S. Chin, and S. Yagihashi Effects of Polyol Pathway Hyperactivity on Protein Kinase C Activity, Nociceptive Peptide Expression, and Neuronal Structure in Dorsal Root Ganglia in Diabetic Mice Diabetes, December 1, 2004; 53(12): 3239 - 3247. [Abstract] [Full Text] [PDF]

				D. Ziegler Polyneuropathy in the diabetic patient--update on pathogenesis and management Nephrol. Dial. Transplant., September 1, 2004; 19(9): 2170 - 2175. [Full Text] [PDF]

				A. M. Vincent, J. W. Russell, P. Low, and E. L. Feldman Oxidative Stress in the Pathogenesis of Diabetic Neuropathy Endocr. Rev., August 1, 2004; 25(4): 612 - 628. [Abstract] [Full Text] [PDF]

				A. J.M. Boulton, R. A. Malik, J. C. Arezzo, and J. M. Sosenko Diabetic Somatic Neuropathies Diabetes Care, June 1, 2004; 27(6): 1458 - 1486. [Full Text] [PDF]

				S. M Setter, R K. Campbell, and C. J Cahoon Biochemical Pathways for Microvascular Complications of Diabetes Mellitus Ann. Pharmacother., December 1, 2003; 37(12): 1858 - 1866. [Abstract] [Full Text] [PDF]

				R. Malik Failure to define the pathogenesis and treatment of human diabetic neuropathy The British Journal of Diabetes & Vascular Disease, March 1, 2003; 3(2): 107 - 111. [Abstract] [PDF]

				I. G. Obrosova, A. G. Minchenko, R. Vasupuram, L. White, O. I. Abatan, A. K. Kumagai, R. N. Frank, and M. J. Stevens Aldose Reductase Inhibitor Fidarestat Prevents Retinal Oxidative Stress and Vascular Endothelial Growth Factor Overexpression in Streptozotocin-Diabetic Rats Diabetes, March 1, 2003; 52(3): 864 - 871. [Abstract] [Full Text] [PDF]

				K. Ekberg, T. Brismar, B.-L. Johansson, B. Jonsson, P. Lindstrom, and J. Wahren Amelioration of Sensory Nerve Dysfunction by C-Peptide in Patients With Type 1 Diabetes Diabetes, February 1, 2003; 52(2): 536 - 541. [Abstract] [Full Text] [PDF]

				M. J. Sheetz and G. L. King Molecular Understanding of Hyperglycemia's Adverse Effects for Diabetic Complications JAMA, November 27, 2002; 288(20): 2579 - 2588. [Abstract] [Full Text] [PDF]

				Z. T. Bloomgarden Neuropathy, Womens' Health, and Socioeconomic Aspects of Diabetes Diabetes Care, June 1, 2002; 25(6): 1085 - 1094. [Full Text] [PDF]