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Long-Term Effects of Ranirestat (AS-3201) on Peripheral Nerve Function in Patients With Diabetic Sensorimotor Polyneuropathy

¹ Department of Medicine, University of Toronto, Toronto, Canada
² Dainippon Pharmaceuticals, Teaneck, New Jersey

Address correspondence and reprint requests to Vera Bril, EN11-209, Toronto General Hospital, University Health Network, 200 Elizabeth St., Toronto, Ontario, Canada, M5G 2C4. E-mail: vera.bril{at}utoronto.ca

OBJECTIVES—We aimed to determine whether ranirestat, an aldose reductase inhibitor, maintains the improved nerve function observed in patients with diabetic sensorimotor polyneuropathy (DSP) after completing a 12-week nerve biopsy study.

RESEARCH DESIGN AND METHODS—Patients with mild to moderate DSP, as determined by the presence of sural nerve responses, were enrolled in a double-blind, placebo-controlled biopsy trial and randomized to placebo or 5 or 20 mg/day ranirestat for 12 weeks. Patients completing this biopsy study were offered a 48-week extension at the same ranirestat dose or at 5 mg/day ranirestat if they were originally treated with placebo. Electrophysiological tests, the Toronto Clinical Neuropathy Score, and vibration perception thresholds (VPTs) were performed at entry and at 12 (end of the biopsy study) and 60 (end of the 48-week extension) weeks.

RESULTS—Peroneal motor nerve conduction velocity (NCV) improved in the 20-mg/day group following 60 weeks of treatment. Sural and median sensory NCV improved after both 12 and 60 weeks of treatment with 20 mg/day. VPT improved after 60 weeks of treatment with 20 mg/day. Ranirestat was well tolerated with no difference in adverse events between the 5- and 20-mg/day groups.

CONCLUSIONS—Twenty milligrams ranirestat per day improves NCV and VPT following 60 weeks of administration. The improved sensory nerve function observed after 12 weeks of therapy was maintained at 60 weeks, and improved motor nerve function was observed at 60 weeks.

Abbreviations: ARI, aldose reductase inhibitor • DSP, diabetic sensorimotor polyneuropathy • NCS, nerve conduction studies • NCV, nerve conduction velocity • TCNS, Toronto Clinical Neuropathy Score • VPT, vibration perception threshold

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