Kusumanto Y H, van Weel V, Mulder N H, Smit A J, van den Dungen J J A M, Hooymans J M M, Sluiter W J, Tio R A, Quax P H A, Gans R O B, Dullaart R P F, Hospers G A P
Department of Internal Medicine, University of Groningen and University Medical Center Groningen, 9700 RB Groningen, The Netherlands.
Hum Gene Ther. 2006 Jun;17(6):683-91. doi: 10.1089/hum.2006.17.683.
Despite advances in revascularization techniques, limb salvage and relief of pain cannot be achieved in many diabetic patients with diffuse peripheral vascular disease. Our objective was to determine the effect of intramuscular administration of phVEGF165 (vascular endothelial growth factor gene-carrying plasmid) on critical limb ischemia (CLI) compared with placebo (0.9% NaCl). A double-blind, placebo-controlled study was performed in 54 adult diabetic patients with CLI. The primary end point was the amputation rate at 100 days. Secondary end points were a 15% increase in pressure indices (ankle-to-brachial index and toe-to-brachial index), clinical improvement (skin, pain, and Quality of Life score), and safety. In patients (n=27) treated with placebo versus phVEGF165-treated patients (n=27) the following results were found: 6 amputations versus 3 (p=not significant [NS]); hemodynamic improvement in 1 versus 7 (p=0.05); improvement in skin ulcers, 0 versus 7 (p=0.01); decrease in pain, 2 versus 5 (p=NS); and overall, 3 versus 14 responding patients (p=0.003). No grade 3 or 4 adverse effects were seen in these patients. We conclude that this small, randomized gene therapy study failed to meet the primary objective of significant amputation reduction. However, significant and meaningful improvement was found in patients treated with a VEGF165-containing plasmid. There were no substantial adverse events.
尽管血管重建技术取得了进展，但许多患有弥漫性外周血管疾病的糖尿病患者仍无法实现肢体挽救和疼痛缓解。我们的目的是确定与安慰剂（0.9%氯化钠）相比，肌肉注射phVEGF165（携带血管内皮生长因子基因的质粒）对严重肢体缺血（CLI）的影响。对54名患有CLI的成年糖尿病患者进行了一项双盲、安慰剂对照研究。主要终点是100天时的截肢率。次要终点是压力指数（踝臂指数和趾臂指数）增加15%、临床改善（皮肤、疼痛和生活质量评分）以及安全性。在接受安慰剂治疗的患者（n = 27）与接受phVEGF165治疗的患者（n = 27）中发现了以下结果：截肢6例与3例（p = 无显著差异[NS]）；血流动力学改善1例与7例（p = 0.05）；皮肤溃疡改善0例与7例（p = 0.01）；疼痛减轻2例与5例（p = NS）；总体而言，有反应的患者3例与14例（p = 0.003）。这些患者未出现3级或4级不良反应。我们得出结论，这项小型随机基因治疗研究未能达到显著降低截肢率的主要目标。然而，在接受含VEGF165质粒治疗的患者中发现了显著且有意义的改善。没有实质性的不良事件。
