Steps against the burden of Parkinson’s disease (StepuP): Protocol of a randomized controlled trial elucidating the biomechanical and neurophysiological mechanisms of a speed dependent treadmill training intervention

OBJECTIVE: Parkinson's disease can impair gait and stability, leading to reduced independence and increased fall risk. While speed dependent treadmill training (SDTT) is clinically effective, the specific biomechanical and neurophysiological mechanisms driving these improvements remain unclear. The "StepuP" multicenter randomized controlled trial aims to elucidate these mechanisms and determine whether training enriched with virtual reality or mechanical perturbations (SDTT+) enhances gait efficacy and transfer to daily life. METHODS: We will recruit 126 individuals with Parkinson's disease across four clinical sites and 21 healthy older adults as a reference group. Participants will be randomized to receive either standard SDTT or SDTT+ for 12 sessions. To capture the trajectory of recovery and retention, assessments will occur at three distinct timepoints: baseline, post-intervention, and a 12-week follow-up, each assessment including synchronized 64-channel electroencephalography (EEG), electromyography (EMG), and 3D kinematics. This multimodal setup allows for the quantification of cortical beta-band activity, corticomuscular coherence, and stability-related foot placement control. Furthermore, we will assess participant's satisfaction, usability, and engagement through questionnaires and interviews to understand individual adherence and barriers to training. SIGNIFICANCE: The primary clinical endpoint is comfortable overground walking speed. We hypothesize that gait improvements are mediated by improved stability-related foot placement and cortical sensorimotor integration. By correlating lab-based mechanistic changes with real-world mobility patterns and participant experiences, this study seeks to identify specific pathophysiological mechanisms engaged during the treadmill training. These insights will help distinguish responders from non-responders, facilitating the development of personalized, acceptable, and effective rehabilitation strategies.

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Journal
PLoS ONE
Published
2026-06-25
DOI
https://doi.org/10.1371/journal.pone.0348957
Primary Topic
Balance, Gait, and Falls Prevention
Type
article
Field-Weighted Citation Impact
0.00

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article

Steps against the burden of Parkinson’s disease (StepuP): Protocol of a randomized controlled trial elucidating the biomechanical and neurophysiological mechanisms of a speed dependent treadmill training intervention

Julius Welzel, Angela Contri, Navrag B. Singh, A.M. van Leeuwen et al.
PLoS ONE
Balance, Gait, and Falls Prevention
article

Steps against the burden of Parkinson’s disease (StepuP): Protocol of a randomized controlled trial elucidating the biomechanical and neurophysiological mechanisms of a speed dependent treadmill training intervention

Julius Welzel, Angela Contri, Navrag B. Singh, A.M. van Leeuwen, Jeffrey M. Hausdorff, Frederic von Wegner, Yoshiro Okubo, Ilaria D’Ascanio, V. Vinod, Sjoerd M. Bruijn, Johanna Geritz, Giovanna Lopane, Walter Maetzler, Clint Hansen, Deepak K. Ravi, Giovanna Calandra–Buonaura, Fabio La Porta, Eran Gazit, Husna Razee, Jaap H. van Dieën, Leonardo Pellicciari, Bernadette C.M. van Wijk, Mayna Ratanapongleka, Ilaria Casadei, Shahar Siman Tov, Noman Zahid, Francesca Tampellini, Revital Prusak, Pia Görrisen, Luca Palmerini, Charlotte Lang, Matthew Brodie, Mehwish Mehwish
article en

Abstract

OBJECTIVE: Parkinson's disease can impair gait and stability, leading to reduced independence and increased fall risk. While speed dependent treadmill training (SDTT) is clinically effective, the specific biomechanical and neurophysiological mechanisms driving these improvements remain unclear. The "StepuP" multicenter randomized controlled trial aims to elucidate these mechanisms and determine whether training enriched with virtual reality or mechanical perturbations (SDTT+) enhances gait efficacy and transfer to daily life. METHODS: We will recruit 126 individuals with Parkinson's disease across four clinical sites and 21 healthy older adults as a reference group. Participants will be randomized to receive either standard SDTT or SDTT+ for 12 sessions. To capture the trajectory of recovery and retention, assessments will occur at three distinct timepoints: baseline, post-intervention, and a 12-week follow-up, each assessment including synchronized 64-channel electroencephalography (EEG), electromyography (EMG), and 3D kinematics. This multimodal setup allows for the quantification of cortical beta-band activity, corticomuscular coherence, and stability-related foot placement control. Furthermore, we will assess participant's satisfaction, usability, and engagement through questionnaires and interviews to understand individual adherence and barriers to training. SIGNIFICANCE: The primary clinical endpoint is comfortable overground walking speed. We hypothesize that gait improvements are mediated by improved stability-related foot placement and cortical sensorimotor integration. By correlating lab-based mechanistic changes with real-world mobility patterns and participant experiences, this study seeks to identify specific pathophysiological mechanisms engaged during the treadmill training. These insights will help distinguish responders from non-responders, facilitating the development of personalized, acceptable, and effective rehabilitation strategies.

PLoS ONEVol. 21(6)
Rush University Medical Center (US), Tel Aviv University (IL), Tel Aviv Sourasky Medical Center (IL), Marconi University (IT), UNSW Sydney (AU), Christian-Albrechts-Universität zu Kiel (DE), ETH Zurich (CH), Institute for Biomedical Engineering (CH), Laboratori Guglielmo Marconi (Italy) (IT), Amsterdam Neuroscience (NL), University Hospital Schleswig-Holstein (DE), Istituto delle Scienze Neurologiche di Bologna (IT), Istituti di Ricovero e Cura a Carattere Scientifico (IT), Neuroscience Research Australia (AU), Vrije Universiteit Amsterdam (NL), University of Lübeck (DE), University of Bologna (IT)
National Science Foundation, Michael J. Fox Foundation for Parkinson's Research, EU Joint Programme – Neurodegenerative Disease Research, Schweizerischer Nationalfonds zur Förderung der Wissenschaftlichen Forschung, University of New South Wales, ZonMw, Ministero della Salute, Medical Research Council, National Health and Medical Research Council
Openalex Percentile: Top 4%
Balance, Gait, and Falls Prevention
DOIOpen Access PDFOpenAlex
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