THE 6‐minute walk test and other endpoints in Duchenne muscular dystrophy: Longitudinal natural history observations over 48 weeks from a multicenter study
Craig M. McDonald,Erik K Henricson,R. Ted Abresch,Julaine Florence,Michelle Eagle,Eduard Gappmaier,Allan M. Glanzman,R. Spiegel,Jay A. Barth,Gary Elfring,A. Reha,Stuart W. Peltz +11 more
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Findings confirm the clinical meaningfulness of the 6MWD as the most accepted primary clinical endpoint in ambulatory DMD trials.Abstract:
Introduction: Duchenne muscular dystrophy (DMD) subjects ≥5 years with nonsense mutations were followed for 48 weeks in a multicenter, randomized, double-blind, placebo-controlled trial of ataluren. Placebo arm data (N = 57) provided insight into the natural history of the 6-minute walk test (6MWT) and other endpoints. Methods: Evaluations performed every 6 weeks included the 6-minute walk distance (6MWD), timed function tests (TFTs), and quantitative strength using hand-held myometry. Results: Baseline age (≥7 years), 6MWD, and selected TFT performance are strong predictors of decline in ambulation (Δ6MWD) and time to 10% worsening in 6MWD. A baseline 6MWD of <350 meters was associated with greater functional decline, and loss of ambulation was only seen in those with baseline 6MWD <325 meters. Only 1 of 42 (2.3%) subjects able to stand from supine lost ambulation. Conclusion: Findings confirm the clinical meaningfulness of the 6MWD as the most accepted primary clinical endpoint in ambulatory DMD trials.read more
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Measuring clinical effectiveness of medicinal products for the treatment of Duchenne muscular dystrophy
Stephen Lynn,Annemieke Aartsma-Rus,Kate Bushby,Pat Furlong,Nathalie Goemans,Annamaria De Luca,Anna Mayhew,Craig M. McDonald,Eugenio Mercuri,Francesco Muntoni,Marita Pohlschmidt,Jan J.G.M. Verschuuren,Thomas Voit,Elizabeth Vroom,Dominic J. Wells,Volker Straub +15 more
TL;DR: The manuscript elaborates on what is clinically meaningful and how to measure this in DMD and what to look out for in patients with DMD.
Journal ArticleDOI
European regulators’ views on a wearable-derived performance measurement of ambulation for Duchenne muscular dystrophy regulatory trials
Marion Haberkamp,Jane Moseley,Dimitrios Athanasiou,Fernando de Andres-Trelles,Andre Elferink,Mário M. Rosa,Armando Magrelli +6 more
TL;DR: European regulators provide an update on the recent regulatory consideration of a new endpoint (Stride Velocity 95th Centile (SV95C) that could be used in therapeutic DMD trials that aims to quantify a patient's ambulation directly, reliably and continuously in a home environment with a wearable device.
Journal ArticleDOI
Pulmonary Endpoints in Duchenne Muscular Dystrophy. A Workshop Summary.
Jonathan D. Finder,Oscar H. Mayer,Daniel W. Sheehan,Hemant Sawnani,R. Ted Abresch,Joshua O. Benditt,David J. Birnkrant,David J. Birnkrant,Tina Duong,Erik K Henricson,Kathi Kinnett,Craig M. McDonald,Anne M. Connolly +12 more
TL;DR: Parent Project Muscular Dystrophy convened a workshop in Bethesda, Maryland, on April 14 and 15, 2016, to summarize published respiratory data in DMD and give guidance to clinical researchers assessing the effect of interventions on pulmonary outcomes in D MD.
Journal ArticleDOI
Meta-analyses of ataluren randomized controlled trials in nonsense mutation Duchenne muscular dystrophy.
Craig Campbell,Richard J. Barohn,Enrico Bertini,Brigitte Chabrol,Giacomo P. Comi,Basil T. Darras,Richard S. Finkel,Kevin M. Flanigan,Nathalie Goemans,Susan T. Iannaccone,Kristi J. Jones,Janbernd Kirschner,Jean K. Mah,Katherine D. Mathews,Craig M. McDonald,Eugenio Mercuri,Yoram Nevo,Yann Péreón,J. Ben Renfroe,Monique M. Ryan,Jacinda B. Sampson,Ulrike Schara,Thomas Sejersen,Kathryn Selby,Mar Tulinius,Juan J. Vílchez,Thomas Voit,Lee-Jen Wei,Brenda L. Wong,Gary Elfring,Marcio Souza,Joseph McIntosh,Panayiota Trifillis,Stuart W. Peltz,Francesco Muntoni +34 more
TL;DR: Meta-analyses support previous evidence for ataluren in slowing disease progression versus placebo in patients with nmDMD over 48 weeks, and treatment benefit was most evident in Patients with a baseline 6MWD ≥300-<400 m (the ambulatory transition phase), thereby informing future trial design.
Journal ArticleDOI
Longitudinal timed function tests in Duchenne muscular dystrophy: ImagingDMD cohort natural history.
Harneet Arora,Rebecca J. Willcocks,Donovan J. Lott,Ann T. Harrington,Claudia R. Senesac,Kirsten L. Zilke,Michael J. Daniels,Dandan Xu,Gihan Tennekoon,Erika Finanger,Barry S. Russman,Richard S. Finkel,William T. Triplett,Barry J. Byrne,Glenn A. Walter,H. Lee Sweeney,Krista Vandenborne +16 more
TL;DR: In this article, the authors provided insight into the contemporary natural history of key functional endpoints in Duchenne muscular dystrophy (DMD) in 5-12.9 year olds.
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TL;DR: A tremendous heterogeneity of severity among males with Becker's muscular dystrophy is suggested, with mean intellectual and neuropsychologic function within normal limits, but with a large variability in intelligence quotient scores.
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TL;DR: A comprehensive set of DMD care recommendations for management of rehabilitation, orthopaedic, respiratory, cardiovascular, gastroenterology/nutrition, and pain issues, as well as general surgical and emergency-room precautions are presented.
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