Lyons Thomas E, Miller Michael S, Serena Thomas, Sheehan Peter, Lavery Lawrence, Kirsner Robert S, Armstrong David G, Reese Amber, Yankee Ernest W, Veves Aristidis
Beth Israel Deaconess Medical Center and Harvard Medical School, Palmer 321 A, West Campus, Boston, MA 02215, USA.
Am J Surg. 2007 Jan;193(1):49-54. doi: 10.1016/j.amjsurg.2006.07.010.
Talactoferrin alfa, a recombinant form of human lactoferrin, is a novel immunomodulatory protein with demonstrated ulcer healing properties in animal models.
A phase 1/2 clinical study was conducted at 7 clinical sites to determine if talactoferrin can improve wound healing in diabetic patients with foot ulceration. Fifty-five patients with diabetic neuropathic foot ulcers participated in this 2-phase study. In phase 1, groups of 3 patients each received open-label 1%, 2.5%, or 8.5% talactoferrin gel twice daily, in a sequential design, to their ulcer for 30 days. No drug-related adverse events were found at any dose level. Phase 2 was a randomized, placebo-controlled, single-blind study of 2.5% and 8.5% gels, with patients equally divided between the 3 groups. In combination with good wound care, treatment was administered topically twice daily to the ulcers for 12 weeks. The primary endpoint was the incidence of > or = 75% healing (relative to baseline size).
The study, which in phase 2 was powered to detect a difference between the placebo and combined talactoferrin arms with P < .1, met the primary objective. The groups receiving the 2.5% (n = 15) and 8.5% (n = 15) gels had twice the incidence of > or = 75% reduction in ulcer size compared with the placebo group (n = 16): 47%, 53%, and 25%, respectively. On an intent-to-treat basis, the combination of the 2 active groups when compared with the placebo group showed a strong trend toward statistical significance (P = .09). There were no talactoferrin-related adverse events or laboratory abnormalities.
Topical talactoferrin appears to be safe and well tolerated and improves healing of diabetic neuropathic ulcers.
α-乳铁蛋白是重组人乳铁蛋白,是一种新型免疫调节蛋白,在动物模型中已证实具有促进溃疡愈合的特性。
在7个临床地点开展了一项1/2期临床研究,以确定α-乳铁蛋白是否能改善糖尿病足溃疡患者的伤口愈合情况。55例糖尿病神经病变性足部溃疡患者参与了这项2期研究。在第1阶段,每组3例患者按序贯设计,每天两次接受开放标签的1%、2.5%或8.5%α-乳铁蛋白凝胶治疗,持续30天,用药于溃疡处。在任何剂量水平均未发现与药物相关的不良事件。第2阶段是一项关于2.5%和8.5%凝胶的随机、安慰剂对照、单盲研究,患者平均分为3组。在良好伤口护理的基础上,每天两次对溃疡进行局部治疗,持续12周。主要终点是愈合≥75%(相对于基线大小)的发生率。
该研究在第2阶段有能力检测安慰剂组和联合α-乳铁蛋白组之间的差异,P<0.1,达到了主要目标。接受2.5%(n = 15)和8.5%(n = 15)凝胶治疗的组溃疡大小减少≥75%的发生率是安慰剂组(n = 16)的两倍:分别为47%、53%和25%。在意向性分析的基础上,两个活性组与安慰剂组相比显示出强烈的统计学显著性趋势(P = 0.09)。没有与α-乳铁蛋白相关的不良事件或实验室异常。
局部应用α-乳铁蛋白似乎安全且耐受性良好,可改善糖尿病神经病变性溃疡的愈合。