G551D, a mutation of the cystic fibrosis transmembrane conductance regulator (CFTR) gene, results in impaired chloride channel function in cystic fibrosis (CF) with multiple end-organ manifestations. The effect of ivacaftor, a CFTR-potentiator, on exercise capacity in CF is unknown. Twenty G551D-CF patients were recruited to a single-centre, double-blind, placebo-controlled, 28-day crossover study of ivacaftor. Variables measured included percentage change from baseline (%Δ) of VO2max (maximal oxygen consumption, primary outcome) during cardiopulmonary exercise testing (CPET), relevant other CPET physiological variables, lung function, body mass index (BMI), sweat chloride and disease-specific health related quality of life (QOL) measures (CFQ-R and Alfred Wellness (AWEscore)). %ΔVO2max was unchanged compared with placebo as was %Δminute ventilation. However, %Δexercise time (mean 7.3, CI 0.5–14,1, P=0.0222) significantly increased as did %ΔFEV1 (11.7%, range 5.3–18.1, P<0·005) and %ΔBMI (1.2%, range 0.1–2.3, P=0·0393) whereas sweat chloride decreased (mean −43.4; range −55.5–18.1 mmol·l−1, P<0·005). Total and activity based domains in both CFQ-R and AWEscore also increased. A positive treatment effect on spirometry, BMI (increased), SCT (decreased) and total and activity based CF-specific QOL measures was expected. However, the lack of discernible improvement in VO2max and VE despite other positive changes including spirometric lung function and exercise time with a 28-day ivacaftor intervention suggests that ventilatory parameters are not the sole driver of change in exercise capacity in this study cohort. Investigation over a more prolonged period may delineate the potential interdependencies of the observed discordances over time. Trial registration number: ClinicalTrials.gov-NCT01937325.
Article navigation
Research Article|
July 17 2017
Improvement in exercise duration, lung function and well-being in G551D-cystic fibrosis patients: a double-blind, placebo-controlled, randomized, cross-over study with ivacaftor treatment
Deirdre Edgeworth
;
Deirdre Edgeworth
1
Cystic Fibrosis Service, The Alfred, Melbourne, Australia
Search for other works by this author on:
Dominic Keating
;
Dominic Keating
1
Cystic Fibrosis Service, The Alfred, Melbourne, Australia3
Department of Medicine, Monash University, Melbourne, Australia
Search for other works by this author on:
Matthew Ellis
;
Matthew Ellis
1
Cystic Fibrosis Service, The Alfred, Melbourne, Australia
Search for other works by this author on:
Brenda Button
;
Brenda Button
1
Cystic Fibrosis Service, The Alfred, Melbourne, Australia2
Department of Physiotherapy, The Alfred, Melbourne, Australia
Search for other works by this author on:
Elyssa Williams
;
Elyssa Williams
1
Cystic Fibrosis Service, The Alfred, Melbourne, Australia
Search for other works by this author on:
Denise Clark
;
Denise Clark
1
Cystic Fibrosis Service, The Alfred, Melbourne, Australia
Search for other works by this author on:
Audrey Tierney
;
Audrey Tierney
1
Cystic Fibrosis Service, The Alfred, Melbourne, Australia4
Department of Nutrition and Dietetics, The Alfred, Melbourne, Australia5
Department of Dietetics and Human Nutrition, La Trobe University, Melbourne, Australia
Search for other works by this author on:
Stephane Heritier
;
Stephane Heritier
1
Cystic Fibrosis Service, The Alfred, Melbourne, Australia6
School of Public Health and Preventative Medicine, Monash University, Melbourne, Australia
Search for other works by this author on:
Tom Kotsimbos
;
Tom Kotsimbos
1
Cystic Fibrosis Service, The Alfred, Melbourne, Australia3
Department of Medicine, Monash University, Melbourne, Australia
Search for other works by this author on:
John Wilson
1
Cystic Fibrosis Service, The Alfred, Melbourne, Australia3
Department of Medicine, Monash University, Melbourne, Australia
Correspondence: John Wilson (john.wilson@monash.edu)
Search for other works by this author on:
Clin Sci (Lond) (2017) 131 (15): 2037-2045.
Article history
Received:
April 23 2017
Revision Received:
June 07 2017
Accepted:
June 12 2017
Accepted Manuscript online:
June 13 2017
Citation
Deirdre Edgeworth, Dominic Keating, Matthew Ellis, Brenda Button, Elyssa Williams, Denise Clark, Audrey Tierney, Stephane Heritier, Tom Kotsimbos, John Wilson; Improvement in exercise duration, lung function and well-being in G551D-cystic fibrosis patients: a double-blind, placebo-controlled, randomized, cross-over study with ivacaftor treatment. Clin Sci (Lond) 1 August 2017; 131 (15): 2037–2045. doi: https://doi.org/10.1042/CS20170995
Download citation file:
Close
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionCited By
Related Articles
Dimeric cystic fibrosis transmembrane conductance regulator exists in the plasma membrane
Biochem J (September, 2003)
Elevation of hepatic sulphotransferase activities in mice with resistance to cystic fibrosis
Biochem J (May, 2002)
The structural basis of cystic fibrosis
Biochem Soc Trans (August, 2018)