Sweat chloride as a biomarker of CFTR activity: Proof of concept and ivacaftor clinical trial data

被引：119

作者：

Accurso, Frank J. ^{[1
,8
]}

Van Goor, Fredrick ^{[2
]}

Zha, Jiuhong ^{[2
]}

Stone, Anne J. ^{[2
]}

Dong, Qunming ^{[2
]}

Ordonez, Claudia L. ^{[2
]}

Rowe, Steven M. ^{[3
]}

Clancy, John Paul ^{[4
]}

Konstan, Michael W. ^{[5
]}

Hoch, Heather E. ^{[1
,8
]}

Heltshe, Sonya L. ^{[6
,9
]}

Ramsey, Bonnie W. ^{[6
,9
]}

Campbell, Preston W. ^{[7
]}

Ashlock, Melissa A. ^{[7
]}

机构：

[1] Univ Colorado Denver, Dept Pediat, Aurora, CO 80045 USA

[2] Vertex Pharmaceut Inc, Cambridge, MA 02139 USA

[3] Univ Alabama Birmingham, Birmingham, AL 35249 USA

[4] Cincinnati Childrens Hosp Med Ctr, Cincinnati, OH 45220 USA

[5] Case Western Reserve Univ, Sch Med, Dept Pediat, Rainbow Babies & Childrens Hosp, Cleveland, OH 44106 USA

[6] Univ Washington, Med Ctr, Seattle Childrens Hosp, Seattle, WA 98195 USA

[7] Cyst Fibrosis Fdn Therapeut, Bethesda, MD 20814 USA

[8] Univ Colorado Denver, Aurora, CO 80045 USA

[9] Seattle Childrens Hosp, Seattle, WA 98105 USA

来源：

JOURNAL OF CYSTIC FIBROSIS | 2014年 / 13卷 / 02期

关键词：

Cystic fibrosis; Nasal potential difference; Variance; Sweat test; NASAL POTENTIAL DIFFERENCE; AIRWAY ION-TRANSPORT; CYSTIC-FIBROSIS; CHANNEL FUNCTION; REGULATOR GENE; IN-VITRO; MUTATION; DIAGNOSIS; PANCREATITIS; GUIDELINES;

D O I：

10.1016/j.jcf.2013.09.007

中图分类号：

R56 [呼吸系及胸部疾病];

学科分类号：

摘要：

Background: We examined data from a Phase 2 trial {NCT00457821} of ivacaftor, a CFTR potentiator, in cystic fibrosis (CF) patients with a G551D 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. (C) 2013 European Cystic Fibrosis Society. Published by Elsevier B.V. All rights reserved.

引用

页码：139 / 147

页数：9

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