Identification of passive wrist-worn accelerometry outcomes for improved disease monitoring and trial design in motor neuron diseaseResearch in context
Summary: Background: Motor neuron disease (MND) leads to progressive functional decline, making reliable measures of disease progression critical for patient care and clinical trials. Current clinical outcome measures lack the ability to continuously and objectively track functional decline in dail...
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Elsevier
2025-07-01
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| Series: | EBioMedicine |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352396425002233 |
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| author | Cory J. Holdom Rakesh Pilkar Christine C. Guo Ruben P.A van Eijk Nadia Sethi Robert D. Henderson Shyuan T. Ngo Frederik J. Steyn |
| author_facet | Cory J. Holdom Rakesh Pilkar Christine C. Guo Ruben P.A van Eijk Nadia Sethi Robert D. Henderson Shyuan T. Ngo Frederik J. Steyn |
| author_sort | Cory J. Holdom |
| collection | DOAJ |
| description | Summary: Background: Motor neuron disease (MND) leads to progressive functional decline, making reliable measures of disease progression critical for patient care and clinical trials. Current clinical outcome measures lack the ability to continuously and objectively track functional decline in daily life of patients with MND. This study assessed and validated wrist-worn accelerometry outcome measures for continuous monitoring in MND, with the potential to refine clinical trial outcomes. Methods: This longitudinal study included 95 patients with MND who wore an ActiGraph GT9X Link device on their non-dominant wrist for 8 days, with follow-up every 3–4 months. Accelerometer data were processed using ActiLife and GGIR. Joint models were used to simultaneously investigate the longitudinal change in ALS Functional Rating Scale-Revised (ALSFRS-R) scores and accelerometer-derived outcomes alongside their relationship with overall survival. Sample size estimates for clinical trials were generated using both accelerometer- and ALSFRS-R-based outcomes, and principal component analysis (PCA) explored outcome relationships. Findings: Accelerometer outcomes showed a slower rate of decline (−0.03 to −0.07 SD/month) compared to ALSFRS-R (−0.10 SD/month) and had stronger correlations with ALSFRS-R motor subdomains (partial r: 0.60–0.73). PCA revealed that longitudinal measures of accelerometry were distinct from the ALSFRS-R, highlighting the complementary nature of these measures. Peak 6-min activity predicted smaller clinical trial sample sizes for studies over 12 months. Accelerometer-derived outcomes were not significantly associated with survival. Interpretation: Wrist-worn accelerometry offers a practical solution for continuous monitoring in MND, complementing ALSFRS-R. Measures of peak performance, and specifically peak 6-min activity shows promise, potentially reducing sample sizes and improving disease tracking over longer duration studies. Further refinement and validation are needed to adopt actigraphy measures as clinical assessment outcomes. Funding: This study was supported by Wesley Medical Research (2016-32), the Honda Foundation, Motor Neurone Disease Research Australia, and FightMND. CJH received a Higher Degree Research Scholarship from UQ. STN received support from the Scott Sullivan Fellowship (MND and Me Foundation/RBWH Foundation), a FightMND Mid-Career Fellowship, and the AIBN. |
| format | Article |
| id | doaj-art-23f4ae1e50574049b6a3d80b36dddbc9 |
| institution | OA Journals |
| issn | 2352-3964 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Elsevier |
| record_format | Article |
| series | EBioMedicine |
| spelling | doaj-art-23f4ae1e50574049b6a3d80b36dddbc92025-08-20T02:37:45ZengElsevierEBioMedicine2352-39642025-07-0111710577910.1016/j.ebiom.2025.105779Identification of passive wrist-worn accelerometry outcomes for improved disease monitoring and trial design in motor neuron diseaseResearch in contextCory J. Holdom0Rakesh Pilkar1Christine C. Guo2Ruben P.A van Eijk3Nadia Sethi4Robert D. Henderson5Shyuan T. Ngo6Frederik J. Steyn7Australian Institute for Bioengineering and Nanotechnology, The University of Queensland, Australia; Corresponding author.ActiGraph, LLC, Pensacola, FL, USAActiGraph, LLC, Pensacola, FL, USADepartment of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, the Netherlands; Biostatistics & Research Support, Julius Center for Health Sciences and Primary Care, University Medical Center Utrecht, Utrecht, the NetherlandsClinical Pharmacogenomics and Precision Medicine, University of Florida, FL, USACentre for Clinical Research, The University of Queensland, Australia; Department of Neurology, Royal Brisbane and Women's Hospital, Brisbane, AustraliaAustralian Institute for Bioengineering and Nanotechnology, The University of Queensland, Australia; Department of Neurology, Royal Brisbane and Women's Hospital, Brisbane, AustraliaDepartment of Neurology, Royal Brisbane and Women's Hospital, Brisbane, Australia; School of Biomedical Sciences, The University of Queensland, Australia; Corresponding author. School of Biomedical Sciences, Faculty of Medicine, The University of Queensland, Australia.Summary: Background: Motor neuron disease (MND) leads to progressive functional decline, making reliable measures of disease progression critical for patient care and clinical trials. Current clinical outcome measures lack the ability to continuously and objectively track functional decline in daily life of patients with MND. This study assessed and validated wrist-worn accelerometry outcome measures for continuous monitoring in MND, with the potential to refine clinical trial outcomes. Methods: This longitudinal study included 95 patients with MND who wore an ActiGraph GT9X Link device on their non-dominant wrist for 8 days, with follow-up every 3–4 months. Accelerometer data were processed using ActiLife and GGIR. Joint models were used to simultaneously investigate the longitudinal change in ALS Functional Rating Scale-Revised (ALSFRS-R) scores and accelerometer-derived outcomes alongside their relationship with overall survival. Sample size estimates for clinical trials were generated using both accelerometer- and ALSFRS-R-based outcomes, and principal component analysis (PCA) explored outcome relationships. Findings: Accelerometer outcomes showed a slower rate of decline (−0.03 to −0.07 SD/month) compared to ALSFRS-R (−0.10 SD/month) and had stronger correlations with ALSFRS-R motor subdomains (partial r: 0.60–0.73). PCA revealed that longitudinal measures of accelerometry were distinct from the ALSFRS-R, highlighting the complementary nature of these measures. Peak 6-min activity predicted smaller clinical trial sample sizes for studies over 12 months. Accelerometer-derived outcomes were not significantly associated with survival. Interpretation: Wrist-worn accelerometry offers a practical solution for continuous monitoring in MND, complementing ALSFRS-R. Measures of peak performance, and specifically peak 6-min activity shows promise, potentially reducing sample sizes and improving disease tracking over longer duration studies. Further refinement and validation are needed to adopt actigraphy measures as clinical assessment outcomes. Funding: This study was supported by Wesley Medical Research (2016-32), the Honda Foundation, Motor Neurone Disease Research Australia, and FightMND. CJH received a Higher Degree Research Scholarship from UQ. STN received support from the Scott Sullivan Fellowship (MND and Me Foundation/RBWH Foundation), a FightMND Mid-Career Fellowship, and the AIBN.http://www.sciencedirect.com/science/article/pii/S2352396425002233Amyotrophic lateral sclerosisClinical outcome measuresActigraphyRemote monitoring |
| spellingShingle | Cory J. Holdom Rakesh Pilkar Christine C. Guo Ruben P.A van Eijk Nadia Sethi Robert D. Henderson Shyuan T. Ngo Frederik J. Steyn Identification of passive wrist-worn accelerometry outcomes for improved disease monitoring and trial design in motor neuron diseaseResearch in context EBioMedicine Amyotrophic lateral sclerosis Clinical outcome measures Actigraphy Remote monitoring |
| title | Identification of passive wrist-worn accelerometry outcomes for improved disease monitoring and trial design in motor neuron diseaseResearch in context |
| title_full | Identification of passive wrist-worn accelerometry outcomes for improved disease monitoring and trial design in motor neuron diseaseResearch in context |
| title_fullStr | Identification of passive wrist-worn accelerometry outcomes for improved disease monitoring and trial design in motor neuron diseaseResearch in context |
| title_full_unstemmed | Identification of passive wrist-worn accelerometry outcomes for improved disease monitoring and trial design in motor neuron diseaseResearch in context |
| title_short | Identification of passive wrist-worn accelerometry outcomes for improved disease monitoring and trial design in motor neuron diseaseResearch in context |
| title_sort | identification of passive wrist worn accelerometry outcomes for improved disease monitoring and trial design in motor neuron diseaseresearch in context |
| topic | Amyotrophic lateral sclerosis Clinical outcome measures Actigraphy Remote monitoring |
| url | http://www.sciencedirect.com/science/article/pii/S2352396425002233 |
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