汗液氯化物作为囊性纤维化跨膜传导调节因子（CFTR）活性的生物标志物：概念验证及依伐卡托临床试验数据
Sweat chloride as a biomarker of CFTR activity: proof of concept and ivacaftor clinical trial data.
作者信息
Accurso Frank J, Van Goor Fredrick, Zha Jiuhong, Stone Anne J, Dong Qunming, Ordonez Claudia L, Rowe Steven M, Clancy John Paul, Konstan Michael W, Hoch Heather E, Heltshe Sonya L, Ramsey Bonnie W, Campbell Preston W, Ashlock Melissa A
出版信息
J Cyst Fibros. 2014 Mar;13(2):139-47. doi: 10.1016/j.jcf.2013.09.007.
Abstract
BACKGROUND
We examined data from a Phase 2 trial {NCT00457821} of ivacaftor, a CFTR potentiator, in cystic fibrosis (CF) patients with aG551D mutation to evaluate standardized approaches to sweat chloride measurement and to explore the use of sweat chloride and nasal potential difference (NPD) to estimate CFTR activity.
METHODS
Sweat chloride and NPD were secondary endpoints in this placebo-controlled, multicenter trial. Standardization of sweat collection, processing,and analysis was employed for the first time. Sweat chloride and chloride ion transport (NPD) were integrated into a model of CFTR activity.
RESULTS
Within-patient sweat chloride determinations showed sufficient precision to detect differences between dose-groups and assess ivacaftor treatment effects. Analysis of changes in sweat chloride and NPD demonstrated that patients treated with ivacaftor achieved CFTR activity equivalent to approximately 35%–40% of normal.
CONCLUSIONS
Sweat chloride is useful in multicenter trials as a biomarker of CFTR activity and to test the effect of CFTR potentiators.
摘要
背景
我们研究了一项针对携带G551D突变的囊性纤维化（CF）患者的CFTR增强剂依伐卡托的2期试验{NCT00457821}的数据，以评估标准化的汗液氯化物测量方法，并探索使用汗液氯化物和鼻电位差（NPD）来估计CFTR活性。
方法
汗液氯化物和NPD是这项安慰剂对照的多中心试验的次要终点。首次采用了汗液收集、处理和分析的标准化方法。汗液氯化物和氯离子转运（NPD）被纳入CFTR活性模型。
结果
患者体内汗液氯化物测定显示出足够的精度，能够检测剂量组之间的差异并评估依伐卡托的治疗效果。对汗液氯化物和NPD变化的分析表明，接受依伐卡托治疗的患者实现的CFTR活性约相当于正常人的35% - 40%。
结论
汗液氯化物在多中心试验中作为CFTR活性的生物标志物以及测试CFTR增强剂的效果是有用的。
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