Vascular Endothelial Growth Factor Gene Transfer for Diabetic Polyneuropathy: A Randomized, Double-Blinded Trial
Vascular Endothelial Growth Factor Gene Transfer for Diabetic Polyneuropathy: A Randomized, Double-Blinded Trial
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DOI：
10.1002/ana.21675
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发表时间：
2009-04-01
影响因子：
11.2
通讯作者：
Losordo, Douglas
中科院分区：
文献类型：
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作者：
Ropper, Allan H.;Gorson, Kenneth C.;Losordo, Douglas
目的：采用质粒血管内皮生长因子（VEGF）肌内基因转移治疗糖尿病多发性神经病的随机、盲法试验。方法：合并多发性神经病变的糖尿病患者随机接受vegf与安慰剂比例为3:1的治疗。在一条腿的坐骨神经、腓神经和胫神经附近的八个标准化部位注射三组。主要结果是6个月时症状评分的变化和预先规定的总体临床和电生理改善评分。次要结果是症状、检查评分、视觉模拟疼痛量表、神经传导和定量感觉测试的差异。结果：39例患者接受质粒VEGF治疗，11例患者接受安慰剂治疗。6个月时，两条腿的平均症状评分均有所改善，VEGF优于安慰剂（-1.2 +/- 0.5 vs -0.9 +/- 0.5；调整未治疗腿的变化后P < 0.01），与未治疗腿相比（-0.7 +/- 0.5;P = 0.02）。治疗组感觉丧失区和视觉模拟疼痛评分改善（-1.5 vs -0.5; p = 0.01）。39例VEGF患者中有12例符合总体改善标准，而11例安慰剂患者中有2例符合总体改善标准。包括神经传导电位在内的其他指标没有改善。VEGF患者不良事件84例，严重不良事件22例；安慰剂组有51个事件，其中2个是严重的。解释：肌内质粒VEGF基因转移改善了糖尿病神经病变症状，满足疗效的主要终点标准，但不影响大多数次要指标。治疗与更严重的不良事件相关，但没有达到统计学意义。这些结果不是结论性的，但可能证明进一步的临床研究是合理的。Ann Neurol 2009；65:386 - 393
Objective: Randomized, blinded trial of intramuscular gene transfer using plasmid vascular endothelial growth factor (VEGF) to treat diabetic polyneuropathy.Methods: Diabetic patients with polyneuropathy were randomized to receive a VEGF-to-placebo ratio of 3:1. Three sets of injections were given at eight standardized sites adjacent to the sciatic, peroneal, and tibial nerves of one leg. Primary outcomes were change in symptom score at 6 months and a prespecified overall clinical and electrophysiological improvement score. Secondary outcomes were differences in symptoms, examination scores, visual analog pain scale, nerve conduction, and quantitative sensory testing.Results: Thirty-nine patients received plasmid VEGF and 11 received placebo. Mean symptom score improved in both legs at 6 months, favoring VEGF over placebo (-1.2 +/- 0.5 vs -0.9 +/- 0.5; P < 0.01 after adjustment for change in the untreated leg) and compared with the untreated leg (-0.7 +/- 0.5; p = 0.02). The region of sensory loss and visual analog pain scale improved in the treated group (-1.5 vs -0.5; p = 0.01). Twelve of 39 VEGF versus 2 of 11 placebo patients met criterion for overall improvement. Other measures including nerve conduction potentials did not improve. There were 84 adverse events in VEGF patients, and 22 were serious; there were 51 events in placebo patients, and 2 were serious.Interpretation: Intramuscular plasmid VEGF gene transfer improved diabetic neuropathic symptoms, meeting primary end-point criteria for efficacy but not affecting most secondary measures. Treatment was associated with more serious adverse events that did not reach statistical significance. These results are not conclusive but may justify further clinical study. Ann Neurol 2009;65:386-393