Long-term effects of ranirestat (AS-3201) on peripheral nerve function in patients with diabetic sensorimotor polyneuropathy
Long-term effects of ranirestat (AS-3201) on peripheral nerve function in patients with diabetic sensorimotor polyneuropathy
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DOI：
10.2337/diacare.29.01.06.dc05-1447
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发表时间：
2006-01-01
期刊：
影响因子：
16.2
通讯作者：
Buchanan, RA
中科院分区：
文献类型：
--
作者：
Bril, V;Buchanan, RA
实验-我们的目的是确定在完成12周的神经活检研究后，在糖尿病感觉运动性多发性神经病（DSP）患者中观察到的一种醛糖还原酶抑制剂ranirestat是否维持神经功能的改善。安慰剂对照活检试验，随机分为安慰剂组或5或20 mg/天的ranirestat组，持续12周。完成该活检研究的患者以相同的ranirestat剂量或5 mg/天ranirestat（如果他们最初用安慰剂治疗）提供48周的延长期。电生理测试，多伦多临床神经病变评分，振动感知阈值（VPT）进行了入口和12（结束活检研究）和60（结束48周的扩展）weeks.RESULTS -腓运动神经传导速度（NCV）改善20毫克/天组60周的治疗。20 mg/天治疗12周和60周后，腓肠神经和正中感觉神经传导速度均有所改善。20 mg/天治疗60周后，VPT改善。Ranirestat耐受性良好，5-和20-mg/day组之间的不良事件没有差异。结论-20毫克的Ranirestat每天改善NCV和VPT后60周的管理。治疗12周后观察到的感觉神经功能改善在60周时得以维持，并且在60周时观察到运动神经功能改善。
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.