Home-based gait analysis as an exploratory endpoint during a multicenter phase 1 trial in limb girdle muscular dystrophy type R2 and facioscapulohumeral muscular dystrophy.
[en] INTRODUCTION/AIMS: Limb girdle muscular dystrophy type 2B (LGMDR2) and facioscapulohumeral muscular dystrophy (FSHD) are genetic muscular dystrophies with an increasing number of potential therapeutic approaches. The aim of this study is to report the data of exploratory digital outcomes extracted from wearable magneto-inertial sensors used in a non-controlled environment for ambulant patients with FSHD and LGMDR2 in a short-term, multicenter clinical study. METHODS: Digital outcomes (stride length, stride speed, and walk parameters in a non-controlled environment) were used as exploratory outcomes in the open-label study ATYR1940-C-004 in ambulant patients during the 3 mo of ATYR1940 treatment and 1 mo of follow-up. Activity and gait variables were calculated from the data recorded in 30-day sub-periods using the sensors. For each sub-period, activity and gait parameters were compared between FSHD and LGMDR2 patients. Change from baseline over the 4-mo study period was assessed. RESULTS: Ten patients (5 FSHD, 5 LGMDR2) were ambulant and compliant for analysis. Gait parameters, but not activity variables, were significantly lower in LGMDR2 compared to FSHD patients at baseline. Longitudinal analyses showed a slight but significant decrease in stride speed at month 4 for all subjects. Activity variables such as total number of strides per day were highly variable from month to month in individual patients, and no visit effects were found for this variable. DISCUSSION: The present study suggests that home-recorded stride speed constitutes a precise and sensitive outcome in ambulant patients with FSHD and LGMDR2.
Disciplines :
Neurology Pediatrics
Author, co-author :
Gidaro, Teresa
Gasnier, Erwan
Annoussamy, Melanie
Vissing, John
Attarian, Shahram
Mozaffar, Tahseen
Iyadurai, Stanley
Wagner, Kathryn R.
Vissière, David
Walker, Gennyne
Shukla, Sanjay S.
Servais, Laurent ; Centre Hospitalier Universitaire de Liège - CHU > Département de Pédiatrie > Service de pédiatrie
Language :
English
Title :
Home-based gait analysis as an exploratory endpoint during a multicenter phase 1 trial in limb girdle muscular dystrophy type R2 and facioscapulohumeral muscular dystrophy.
Publication date :
2022
Journal title :
Muscle and Nerve
ISSN :
0148-639X
eISSN :
1097-4598
Publisher :
John Wiley & Sons, Hoboken, United States - New York
Malik A, Hayat G, Kalia JS, Guzman MA. Idiopathic inflammatory myopathies: clinical approach and management. Front Neurol. 2016;7:64. doi:10.3389/fneur.2016.00064
Cohen J, DeSimone A, Lek M, Lek A. Therapeutic approaches in facioscapulohumeral muscular dystrophy. Trends Mol Med. 2020;27:123-137. doi:10.1016/j.molmed.2020.09.008
Lilien C, Gasnier E, Gidaro T, et al. Home-based monitor for gait and activity analysis. J Vis Exp. 2019;150. doi:10.3791/59668
Le Moing AG, Seferian AM, Moraux A, et al. A movement monitor based on magneto-inertial sensors for non-ambulant patients with Duchenne muscular dystrophy: a pilot study in controlled environment. PLoS One. 2016;11(6):e0156696. doi:10.1371/journal.pone.0156696
Haberkamp M, Moseley J, Athanasiou D, et al. European regulators’ views on a wearable-derived performance measurement of ambulation for Duchenne muscular dystrophy regulatory trials. Neuromuscul Disord. 2019;29(7):514-516. doi:10.1016/j.nmd.2019.06.003
Tasca G, Monforte M, Ottaviani P, et al. Magnetic resonance imaging in a large cohort of facioscapulohumeral muscular dystrophy patients: pattern refinement and implications for clinical trials. Ann Neurol. 2016;79(5):854-864. doi:10.1002/ana.24640
Walter MC, Reilich P, Thiele S, et al. Treatment of dysferlinopathy with deflazacort: a double-blind, placebo-controlled clinical trial. Orphanet J Rare Dis. 2013;8:26. doi:10.1186/1750-1172-8-26
Goselink RJM, Schreuder THA, Mul K, et al. Muscle ultrasound is a responsive biomarker in facioscapulohumeral dystrophy. Neurology. 2020;94(14):e1488-e1494. doi:10.1212/WNL.0000000000009211
Statland JM, Heatwole C, Eichinger K, Dilek N, Martens WB, Tawil R. Electrical impedance myography in facioscapulohumeral muscular dystrophy. Muscle Nerve. 2016;54(4):696-701. doi:10.1002/mus.25065
Gaudreault N, Gravel D, Nadeau S, Houde S, Gagnon D. Gait patterns comparison of children with Duchenne muscular dystrophy to those of control subjects considering the effect of gait velocity. Gait Posture. 2010;32(3):342-347. doi:10.1016/j.gaitpost.2010.06.003
Doglio L, Pavan E, Pernigotti I, Petralia P, Frigo C, Minetti C. Early signs of gait deviation in Duchenne muscular dystrophy. Eur J Phys Rehabil Med. 2011;47(4):587-594.
Rijken NH, van Engelen BG, de Rooy JW, Weerdesteyn V, Geurts AC. Gait propulsion in patients with facioscapulohumeral muscular dystrophy and ankle plantarflexor weakness. Gait Posture. 2015;41(2):476-481. doi:10.1016/j.gaitpost.2014.11.013
Poleur M, Ulinici A, Daron A, et al. Normative data on spontaneous stride velocity, stride length and walking activity in a non-controlled environment. Orphanet J Rare Dis. 2021;16:318.
Annoussamy M, Seferian AM, Daron A, et al. Natural history of type 2 and 3 spinal muscular atrophy: 2-year NatHis-SMA study. Ann Clin Transl Neurol. 2020;8:359-373. doi:10.1002/acn3.51281
Statland JM, Karanevich A, Bruetsch A, Huisinga J. A pilot study of the responsiveness of wireless motion analysis in facioscapulohumeral muscular dystrophy. Muscle Nerve. 2019;60(5):590-594. doi:10.1002/mus.26681