Treatment effect of idebenone on inspiratory function in patients with Duchenne muscular dystrophy

for the DELOS Study Group

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Assessment of dynamic inspiratory function may provide valuable information about the degree and progression of pulmonary involvement in patients with Duchenne muscular dystrophy (DMD). The aims of this study were to characterize inspiratory function and to assess the efficacy of idebenone on this pulmonary function outcome in a large and well-characterized cohort of 10–18 year-old DMD patients not taking glucocorticoid steroids (GCs) enrolled in the phase 3 randomized controlled DELOS trial. We evaluated the effect of idebenone on the highest flow generated during an inspiratory FVC maneuver (maximum inspiratory flow; V'I,max(FVC)) and the ratio between the largest inspiratory flow during tidal breathing (tidal inspiratory flow; V'I,max(t)) and the V'I,max(FVC). The fraction of the maximum flow that is not used during tidal breathing has been termed inspiratory flow reserve (IFR). DMD patients in both treatment groups of DELOS (idebenone, n = 31; placebo: n = 33) had comparable and abnormally low V'I,max(FVC) at baseline. During the study period, V'I,max(FVC) further declined by −0.29 L/sec in patients on placebo (95%CI: −0.51, −0.08; P = 0.008 at week 52), whereas it remained stable in patients on idebenone (change from baseline to week 52: 0.01 L/sec; 95%CI: −0.22, 0.24; P = 0.950). The between-group difference favoring idebenone was 0.27 L/sec (P = 0.043) at week 26 and 0.30 L/sec (P = 0.061) at week 52. In addition, during the study period, IFR improved by 2.8% in patients receiving idebenone and worsened by −3.0% among patients on placebo (between-group difference 5.8% at week 52; P = 0.040). Although the clinical interpretation of these data is currently limited due to the scarcity of routine clinical practice experience with dynamic inspiratory function outcomes in DMD, these findings from a randomized controlled study nevertheless suggest that idebenone preserved inspiratory muscle function as assessed by V'I,max(FVC) and IFR in patients with DMD. Pediatr Pulmonol. 2017;52:508–515.

Original languageEnglish (US)
Pages (from-to)508-515
Number of pages8
JournalPediatric Pulmonology
Volume52
Issue number4
DOIs
StatePublished - Apr 1 2017

Fingerprint

Duchenne Muscular Dystrophy
Placebos
Therapeutics
Respiration
Lung
idebenone
Glucocorticoids
Randomized Controlled Trials
Steroids
Muscles

Keywords

  • Duchenne muscular dystrophy
  • idebenone
  • inspiratory flow
  • respiratory function

ASJC Scopus subject areas

  • Pediatrics, Perinatology, and Child Health
  • Pulmonary and Respiratory Medicine

Cite this

Treatment effect of idebenone on inspiratory function in patients with Duchenne muscular dystrophy. / for the DELOS Study Group.

In: Pediatric Pulmonology, Vol. 52, No. 4, 01.04.2017, p. 508-515.

Research output: Contribution to journalArticle

@article{17d991470ff64290a2a488d5565d8b0f,
title = "Treatment effect of idebenone on inspiratory function in patients with Duchenne muscular dystrophy",
abstract = "Assessment of dynamic inspiratory function may provide valuable information about the degree and progression of pulmonary involvement in patients with Duchenne muscular dystrophy (DMD). The aims of this study were to characterize inspiratory function and to assess the efficacy of idebenone on this pulmonary function outcome in a large and well-characterized cohort of 10–18 year-old DMD patients not taking glucocorticoid steroids (GCs) enrolled in the phase 3 randomized controlled DELOS trial. We evaluated the effect of idebenone on the highest flow generated during an inspiratory FVC maneuver (maximum inspiratory flow; V'I,max(FVC)) and the ratio between the largest inspiratory flow during tidal breathing (tidal inspiratory flow; V'I,max(t)) and the V'I,max(FVC). The fraction of the maximum flow that is not used during tidal breathing has been termed inspiratory flow reserve (IFR). DMD patients in both treatment groups of DELOS (idebenone, n = 31; placebo: n = 33) had comparable and abnormally low V'I,max(FVC) at baseline. During the study period, V'I,max(FVC) further declined by −0.29 L/sec in patients on placebo (95{\%}CI: −0.51, −0.08; P = 0.008 at week 52), whereas it remained stable in patients on idebenone (change from baseline to week 52: 0.01 L/sec; 95{\%}CI: −0.22, 0.24; P = 0.950). The between-group difference favoring idebenone was 0.27 L/sec (P = 0.043) at week 26 and 0.30 L/sec (P = 0.061) at week 52. In addition, during the study period, IFR improved by 2.8{\%} in patients receiving idebenone and worsened by −3.0{\%} among patients on placebo (between-group difference 5.8{\%} at week 52; P = 0.040). Although the clinical interpretation of these data is currently limited due to the scarcity of routine clinical practice experience with dynamic inspiratory function outcomes in DMD, these findings from a randomized controlled study nevertheless suggest that idebenone preserved inspiratory muscle function as assessed by V'I,max(FVC) and IFR in patients with DMD. Pediatr Pulmonol. 2017;52:508–515.",
keywords = "Duchenne muscular dystrophy, idebenone, inspiratory flow, respiratory function",
author = "{for the DELOS Study Group} and Buyse, {Gunnar M.} and Thomas Voit and Ulrike Schara and Straathof, {Chiara S.M.} and D'Angelo, {Maria Grazia} and G{\"u}nther Bernert and Cuisset, {Jean Marie} and Finkel, {Richard S.} and Nathalie Goemans and Christian Rummey and Mika Leinonen and Mayer, {Oscar H.} and Paolo Spagnolo and Thomas Meier and McDonald, {Craig M.} and F. Knipp and {Van den Hauwe}, M. and V. Doppler and T. Gidaro and S. Coopman and S. Lutz and J. Kirschner and S. Borell and M. Will and E. Brighina and S. Gandossini and K. Gorni and E. Falcier and L. Politano and P. D’Ambrosio and A. Taglia and Verschuuren, {J. J.G.M.} and {V{\'i}lchez Padilla}, {J. J.} and {Muelas G{\'o}mez}, N. and T. Sejersen and M. Hovm{\"o}ller and Jeannet, {P. Y.} and C. Bloetzer and S. Iannaccone and D. Castro and G. Tennekoon and R. Finkel and C. B{\"o}nnemann and C. McDonald and E. Henricson and N. Joyce and S. Apkon and Richardson, {R. C.}",
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T1 - Treatment effect of idebenone on inspiratory function in patients with Duchenne muscular dystrophy

AU - for the DELOS Study Group

AU - Buyse, Gunnar M.

AU - Voit, Thomas

AU - Schara, Ulrike

AU - Straathof, Chiara S.M.

AU - D'Angelo, Maria Grazia

AU - Bernert, Günther

AU - Cuisset, Jean Marie

AU - Finkel, Richard S.

AU - Goemans, Nathalie

AU - Rummey, Christian

AU - Leinonen, Mika

AU - Mayer, Oscar H.

AU - Spagnolo, Paolo

AU - Meier, Thomas

AU - McDonald, Craig M.

AU - Knipp, F.

AU - Van den Hauwe, M.

AU - Doppler, V.

AU - Gidaro, T.

AU - Coopman, S.

AU - Lutz, S.

AU - Kirschner, J.

AU - Borell, S.

AU - Will, M.

AU - Brighina, E.

AU - Gandossini, S.

AU - Gorni, K.

AU - Falcier, E.

AU - Politano, L.

AU - D’Ambrosio, P.

AU - Taglia, A.

AU - Verschuuren, J. J.G.M.

AU - Vílchez Padilla, J. J.

AU - Muelas Gómez, N.

AU - Sejersen, T.

AU - Hovmöller, M.

AU - Jeannet, P. Y.

AU - Bloetzer, C.

AU - Iannaccone, S.

AU - Castro, D.

AU - Tennekoon, G.

AU - Finkel, R.

AU - Bönnemann, C.

AU - McDonald, C.

AU - Henricson, E.

AU - Joyce, N.

AU - Apkon, S.

AU - Richardson, R. C.

PY - 2017/4/1

Y1 - 2017/4/1

N2 - Assessment of dynamic inspiratory function may provide valuable information about the degree and progression of pulmonary involvement in patients with Duchenne muscular dystrophy (DMD). The aims of this study were to characterize inspiratory function and to assess the efficacy of idebenone on this pulmonary function outcome in a large and well-characterized cohort of 10–18 year-old DMD patients not taking glucocorticoid steroids (GCs) enrolled in the phase 3 randomized controlled DELOS trial. We evaluated the effect of idebenone on the highest flow generated during an inspiratory FVC maneuver (maximum inspiratory flow; V'I,max(FVC)) and the ratio between the largest inspiratory flow during tidal breathing (tidal inspiratory flow; V'I,max(t)) and the V'I,max(FVC). The fraction of the maximum flow that is not used during tidal breathing has been termed inspiratory flow reserve (IFR). DMD patients in both treatment groups of DELOS (idebenone, n = 31; placebo: n = 33) had comparable and abnormally low V'I,max(FVC) at baseline. During the study period, V'I,max(FVC) further declined by −0.29 L/sec in patients on placebo (95%CI: −0.51, −0.08; P = 0.008 at week 52), whereas it remained stable in patients on idebenone (change from baseline to week 52: 0.01 L/sec; 95%CI: −0.22, 0.24; P = 0.950). The between-group difference favoring idebenone was 0.27 L/sec (P = 0.043) at week 26 and 0.30 L/sec (P = 0.061) at week 52. In addition, during the study period, IFR improved by 2.8% in patients receiving idebenone and worsened by −3.0% among patients on placebo (between-group difference 5.8% at week 52; P = 0.040). Although the clinical interpretation of these data is currently limited due to the scarcity of routine clinical practice experience with dynamic inspiratory function outcomes in DMD, these findings from a randomized controlled study nevertheless suggest that idebenone preserved inspiratory muscle function as assessed by V'I,max(FVC) and IFR in patients with DMD. Pediatr Pulmonol. 2017;52:508–515.

AB - Assessment of dynamic inspiratory function may provide valuable information about the degree and progression of pulmonary involvement in patients with Duchenne muscular dystrophy (DMD). The aims of this study were to characterize inspiratory function and to assess the efficacy of idebenone on this pulmonary function outcome in a large and well-characterized cohort of 10–18 year-old DMD patients not taking glucocorticoid steroids (GCs) enrolled in the phase 3 randomized controlled DELOS trial. We evaluated the effect of idebenone on the highest flow generated during an inspiratory FVC maneuver (maximum inspiratory flow; V'I,max(FVC)) and the ratio between the largest inspiratory flow during tidal breathing (tidal inspiratory flow; V'I,max(t)) and the V'I,max(FVC). The fraction of the maximum flow that is not used during tidal breathing has been termed inspiratory flow reserve (IFR). DMD patients in both treatment groups of DELOS (idebenone, n = 31; placebo: n = 33) had comparable and abnormally low V'I,max(FVC) at baseline. During the study period, V'I,max(FVC) further declined by −0.29 L/sec in patients on placebo (95%CI: −0.51, −0.08; P = 0.008 at week 52), whereas it remained stable in patients on idebenone (change from baseline to week 52: 0.01 L/sec; 95%CI: −0.22, 0.24; P = 0.950). The between-group difference favoring idebenone was 0.27 L/sec (P = 0.043) at week 26 and 0.30 L/sec (P = 0.061) at week 52. In addition, during the study period, IFR improved by 2.8% in patients receiving idebenone and worsened by −3.0% among patients on placebo (between-group difference 5.8% at week 52; P = 0.040). Although the clinical interpretation of these data is currently limited due to the scarcity of routine clinical practice experience with dynamic inspiratory function outcomes in DMD, these findings from a randomized controlled study nevertheless suggest that idebenone preserved inspiratory muscle function as assessed by V'I,max(FVC) and IFR in patients with DMD. Pediatr Pulmonol. 2017;52:508–515.

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KW - idebenone

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KW - respiratory function

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