Stride Velocity 95 th Centile Detects Decline in Ambulatory Function Over Shorter Intervals than the 6-Minute Walk Test or North Star Ambulatory Assessment in Duchenne Muscular Dystrophy
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| Titel: | Stride Velocity 95 th Centile Detects Decline in Ambulatory Function Over Shorter Intervals than the 6-Minute Walk Test or North Star Ambulatory Assessment in Duchenne Muscular Dystrophy |
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| Autoren: | Rabbia, Michael, Guridi Ormazabal, Maitea, Staunton, Hannah, Veenstra, Klaas, Eggenspieler, Damien, Annoussamy, Mélanie, Servais, Laurent, Strijbos, Paul |
| Quelle: | J Neuromuscul Dis |
| Verlagsinformationen: | SAGE Publications, 2024. |
| Publikationsjahr: | 2024 |
| Schlagwörter: | Research Report, Male, Pédiatrie, Walking/physiology, Walk Test, Walking, Pediatrics, Sciences de la santé humaine, Wearable Electronic Devices, 03 medical and health sciences, 0302 clinical medicine, Outcome Assessment, Health Care, Humans, Human health sciences, Child, digital endpoints, clinical trials, ambulation, Muscular Dystrophy, Duchenne/drug therapy, Muscular Dystrophy, Duchenne, dystrophy, Muscular Dystrophy, Duchenne/physiopathology, Neurology, muscular, stride velocity 95th centile, Female, Neurology (clinical) |
| Beschreibung: | Background: Stride Velocity 95 th Centile (SV95C) is the first wearable device-derived clinical outcome assessment (COA) to receive European Medicines Agency (EMA) qualification as a primary endpoint in ambulant patients with Duchenne muscular dystrophy (DMD) aged ≥4 years. Objective: To compare SV95C—in its first-ever clinical trial application as a secondary endpoint—with established motor function COAs used in the trial (Four-Stair Climb [4SC] velocity, North Star Ambulatory Assessment [NSAA], and Six-Minute Walk Distance [6MWD]). Methods: SV95C was a secondary endpoint in a subset ( n = 47) of participants in the SPITFIRE/WN40227 trial of taldefgrobep alfa, which was discontinued due to lack of clinical benefit. Participants in the ≤48-week SV95C sub-study were 6–11 years old and received corticosteroids for ≥6 months pre-treatment. Pearson correlations were used to compare SV95C with the other COAs. Responsiveness and changes over time were respectively assessed via standardized response means (SRMs) based on absolute changes and mixed models for repeated measures. Results: SV95C change at Week 24 was –0.07 m/s, with limited variability (standard deviation: 0.16, n = 27). The SRM for SV95C indicated moderate responsiveness to clinical change at the earliest timepoint (Week 12, n = 46), while those of the other COAs did not indicate moderate responsiveness until Week 36 (6MWD, n = 33) or Week 48 (4SC velocity, n = 20; NSAA total score, n = 20). Baseline correlations between SV95C and other COAs were strong ( r = 0.611–0.695). Correlations between SV95C change from baseline to Week 48 and changes in other COAs were moderate to strong ( r = 0.443–0.678).∥ Conclusions: Overall, SV95C demonstrated sensitivity to ambulatory decline over short intervals, low variability, and correlation with established COAs. Although the negative trial precluded demonstration of SV95C’s sensitivity to drug effect, these findings support the continued use of SV95C in DMD clinical trials. |
| Publikationsart: | Article Other literature type |
| Sprache: | English |
| ISSN: | 2214-3602 2214-3599 |
| DOI: | 10.3233/jnd-230188 |
| Zugangs-URL: | https://pubmed.ncbi.nlm.nih.gov/38640165 |
| Rights: | CC BY NC URL: https://journals.sagepub.com/page/policies/text-and-data-mining-license URL: http://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution (CC BY 4.0) License (http://creativecommons.org/licenses/by/4.0/) . |
| Dokumentencode: | edsair.doi.dedup.....f3704503c502c303f754b1d44db7cd1e |
| Datenbank: | OpenAIRE |
Nájsť tento článok vo Web of Science | Abstract: | Background: Stride Velocity 95 th Centile (SV95C) is the first wearable device-derived clinical outcome assessment (COA) to receive European Medicines Agency (EMA) qualification as a primary endpoint in ambulant patients with Duchenne muscular dystrophy (DMD) aged ≥4 years. Objective: To compare SV95C—in its first-ever clinical trial application as a secondary endpoint—with established motor function COAs used in the trial (Four-Stair Climb [4SC] velocity, North Star Ambulatory Assessment [NSAA], and Six-Minute Walk Distance [6MWD]). Methods: SV95C was a secondary endpoint in a subset ( n = 47) of participants in the SPITFIRE/WN40227 trial of taldefgrobep alfa, which was discontinued due to lack of clinical benefit. Participants in the ≤48-week SV95C sub-study were 6–11 years old and received corticosteroids for ≥6 months pre-treatment. Pearson correlations were used to compare SV95C with the other COAs. Responsiveness and changes over time were respectively assessed via standardized response means (SRMs) based on absolute changes and mixed models for repeated measures. Results: SV95C change at Week 24 was –0.07 m/s, with limited variability (standard deviation: 0.16, n = 27). The SRM for SV95C indicated moderate responsiveness to clinical change at the earliest timepoint (Week 12, n = 46), while those of the other COAs did not indicate moderate responsiveness until Week 36 (6MWD, n = 33) or Week 48 (4SC velocity, n = 20; NSAA total score, n = 20). Baseline correlations between SV95C and other COAs were strong ( r = 0.611–0.695). Correlations between SV95C change from baseline to Week 48 and changes in other COAs were moderate to strong ( r = 0.443–0.678).∥ Conclusions: Overall, SV95C demonstrated sensitivity to ambulatory decline over short intervals, low variability, and correlation with established COAs. Although the negative trial precluded demonstration of SV95C’s sensitivity to drug effect, these findings support the continued use of SV95C in DMD clinical trials. |
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| ISSN: | 22143602 22143599 |
| DOI: | 10.3233/jnd-230188 |