Imperial College London
Alternate

ProfessorJaneDavies

Faculty of Medicine, National Heart & Lung Institute

Professor of Paediatric Respirology & Experimental Medicine
 
 
 
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Contact

 

+44 (0)20 7594 7973j.c.davies

 
 
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Assistant

 

Mrs Gina Rivellini +44 (0)20 7594 7986

 
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Location

 

G44Emmanuel Kaye BuildingRoyal Brompton Campus

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Summary

 

Publications

Citation

BibTex format

@article{Vermeulen:2016:10.1016/j.jcf.2016.02.015,
author = {Vermeulen, F and Le, Camus C and Davies, JC and Bilton, D and Milenkovic, D and De, Boeck K},
doi = {10.1016/j.jcf.2016.02.015},
journal = {Journal of Cystic Fibrosis},
pages = {36--40},
title = {Variability of sweat chloride concentration in subjects with cystic fibrosis and G551D mutations},
url = {http://dx.doi.org/10.1016/j.jcf.2016.02.015},
volume = {16},
year = {2016}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Introduction:Sweat chloride concentration, a biomarker of CFTR function, is an appropriate outcome parameter in clinical trials aimed at correcting the basic CF defect. Although there is consensus on a cut-off value to diagnose CF, we have only limited information on the within subject variability of sweat chloride over time. Such information would be useful for sample size calculations in clinical trials. Therefore, we retrospectively analyzed repeated sweat chloride values obtained in patients with G551D mutation(s) assigned to placebo in an ivacaftor interventional trial.Methods:In subjects with G551D at least 12 years of age, a pilocarpine sweat test using Macroduct collector was taken on both arms at 8 time points over 48 weeks. We explored 1062 pilocarpine sweat test values obtained in 78 placebo patients of the VX08-770-102 trial.Results:Mean overall sweat chloride value (all patients, all tests, n = 1062) was 100.8 mmol/L (SD 12.7 mmol/L). Using a multilevel mixed model, the between-subject standard deviation (SD) for sweat chloride was 8.9 mmol/L (95% CI 7.4–10.6) and within-subject SD was 8.1 mmol/L (95% CI 7.5–8.7). Limits of repeatability for repeat measurements were − 19.7 to + 21.6 mmol/L using values from one arm, and − 13.3 to 11.8 mmol/L using mean of values obtained at 4 test occasions. Sample size calculations showed that the minimal treatment effect on sweat chloride concentration that can be demonstrated for a group of 5 patients is around 15 mmol/L, using a cross-over design and combinations of 4 tests for each phase of the trial. Conclusion:Although the sweat test is considered a robust measure, sweat chloride measurements in patients with CF and a G551D mutation had an inherent biological variability that is higher than commonly considered. Further analyses of placebo group data are crucial to learn more about the natural variability of this outcome parameter.
AU  - Vermeulen,F
AU  - Le,Camus C
AU  - Davies,JC
AU  - Bilton,D
AU  - Milenkovic,D
AU  - De,Boeck K
DO  - 10.1016/j.jcf.2016.02.015
EP  - 40
PY  - 2016///
SN  - 1569-1993
SP  - 36
TI  - Variability of sweat chloride concentration in subjects with cystic fibrosis and G551D mutations
T2  - Journal of Cystic Fibrosis
UR  - http://dx.doi.org/10.1016/j.jcf.2016.02.015
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000393629700008&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - http://hdl.handle.net/10044/1/57215
VL  - 16
ER  -
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