Improvement in exercise duration, lung function and well-being in G551D-Cystic Fibrosis patients: a double-blind, placebo-controlled, randomised, cross-over study with ivacaftor

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 cystic fibrosis (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 (%) of VO2max (maximal oxygen consumption, primary outcome) during cardiopulmonary exercise testing (CPET), relevant other CPET physiological variables, lung function, BMI, sweat chloride, and disease specific health related quality of life (QOL) measures (CFQ-R and Alfred Wellness (AWEscore)). %VO2max was unchanged compared to placebo as was %minute ventilation. However, %exercise time (mean 7.3, CI 0.5-14,1, p=0.0222) significantly increased as did %FEV1 (11·7%, range 5.3-18.1, p<0·005) and %BMI (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 spirometri...
Source: Clinical Science - Category: Biomedical Science Authors: Tags: PublishAheadOfPrint Source Type: research