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

J Cyst Fibros. 2014 Mar;13(2):139-47. doi: 10.1016/j.jcf.2013.09.007.


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.

Publication types

  • Clinical Trial, Phase II
  • Multicenter Study
  • Randomized Controlled Trial

MeSH terms

  • Adult
  • Aminophenols / pharmacology*
  • Biomarkers
  • Child
  • Chlorides* / analysis
  • Chlorides* / metabolism
  • Cystic Fibrosis / drug therapy
  • Cystic Fibrosis / genetics
  • Cystic Fibrosis / metabolism
  • Cystic Fibrosis Transmembrane Conductance Regulator* / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator* / metabolism
  • Dose-Response Relationship, Drug
  • Double-Blind Method
  • Drug Monitoring / methods
  • Female
  • Humans
  • Male
  • Mutation
  • Nasal Mucosa* / metabolism
  • Nasal Mucosa* / physiopathology
  • Quinolones / pharmacology*
  • Reproducibility of Results
  • Respiratory System Agents / pharmacology
  • Specimen Handling / methods
  • Specimen Handling / standards
  • Sweat* / chemistry
  • Sweat* / metabolism
  • Treatment Outcome


  • Aminophenols
  • Biomarkers
  • Chlorides
  • Quinolones
  • Respiratory System Agents
  • Cystic Fibrosis Transmembrane Conductance Regulator
  • ivacaftor

Associated data

  • ClinicalTrials.gov/NCT00457821