Clinical Efficacy of Fidarestat, a Novel Aldose Reductase Inhibitor, for Diabetic Peripheral Neuropathy
A 52-week multicenter placebo-controlled double-blind parallel group study
- Nigishi Hotta, MD1,
- Takayoshi Toyota, MD2,
- Kempei Matsuoka, MD3,
- Yukio Shigeta, MD4,
- Ryuichi Kikkawa, MD5,
- Toshio Kaneko, MD6,
- Akira Takahashi, MD7,
- Kimiya Sugimura, MD8,
- Yasuo Koike, MD9,
- Jun Ishii, MD10,
- Nobuo Sakamoto, MD11 and
- The SNK-860 Diabetic Neuropathy Study Group
- 1Third Department of Internal Medicine, Nagoya University School of Medicine, Nagoya
- 2Third Department of Internal Medicine, School of Medicine, Tohoku University, Sendai
- 3Department of Internal Medicine, Tokyo Saiseikai Central Hospital, Tokyo
- 4Shiga University of Medical Science, Ohtsu
- 5Third Department of Medicine, Shiga University of Medical Science, Ohtsu
- 6Yamaguchi Rosai Hospital, Ube
- 7Tokai Central Hospital, Kagamigahara
- 8Nagoya University College of Medical Technology, Nagoya
- 9Neurophysiology Section, Department of Examination, Nagoya University, Nagoya
- 10Fourth Department of Internal Medicine, Saitama Medical School, Saitama
- 11Chubu Rosai Hospital, Nagoya, Japan
Abstract
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.
- AR, aldose reductase
- FCV, F-wave conduction velocity
- MNCV, motor nerve conduction velocity
- SNCV, sensory nerve conduction velocity
Footnotes
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Address correspondence and reprint requests to Nigishi Hotta, MD, Third Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsuruma-cho, Showa-ku, Nagoya 466-8550, Japan. E-mail: hotta{at}chubuh.rofuku.go.jp.
Received for publication 6 February 2001 and accepted in revised form 19 June 2001.
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