Steps Against the Burden of Parkinson's Disease (StepuP)

StepuP: Steps Against the Burden of Parkinson's Disease

Parkinson's Disease Treadmill Training RCT Summary

Parkinson's disease (PD) affects over 10 million people globally. Despite optimal pharmacological treatment, approximately 70% of individuals experience unstable gait and falls, leading to loss of confidence, social isolation, fractures, and frequent hospitalisations. Treadmill training-especially when augmented by mechanical or virtual-reality perturbations-has shown promise in improving gait and reducing fall risk. However, the mechanisms underlying these benefits remain poorly understood, limiting the ability to personalise interventions effectively.

This randomised controlled trial (RCT) forms part of the broader Steps Against the Burden of Parkinson's Disease project (CT-IDs: 6ef2e427b002, 6ef2e427b003, 6ef2e427b004), comprising three harmonised but independently conducted RCTs. All sites follow a shared core protocol, allowing for pooled data analysis while preserving site-specific perturbation adaptations. Findings from this trial will be reported both independently and as part of the combined dataset.

In this trial, participants with PD will undergo 12 sessions of treadmill training, with or without virtual reality and perturbation-based adaptations. Assessments will be conducted at baseline, post-training, and follow-up. The intervention aims to enhance gait through improved sensorimotor integration and balance control. During the follow-up period, a smartphoneapp "Walking Tall" will be used to encourage continued exercises and long-term retention of training effects.

Biomechanical analyses will focus on changes in foot placement control. Neurophysiological outcomes will be examined using EEG and EMG, targeting reductions in beta-band EEG power and enhanced EEG-EMG coherence as markers of improved gait stability.

Recognising that laboratory-based improvements may not always translate to daily life, this study will also investigate gait self-efficacy as a potential moderator of transfer. Remote monitoring tools will capture real-world mobility outcomes over a week. Machine learning techniques will be employed to identify factors differentiating those who improve in both settings from those who do not. These insights will inform the development of personalised interventions capable of translating training effects into meaningful real-life outcomes.

Study Overview

• Status: Recruiting
• Conditions: Parkinson Disease (PD)
• Intervention / Treatment: Other: Exercise; Other: Exercise

Detailed Description

i. Rationale The rationale of this trial is that speed-dependent treadmill training (SDTT) improves gait in people with Parkinson's disease (PD) through enhanced sensorimotor integration, with cortical activity changes as underlying neural correlates. Additional benefits may be gained when treadmill training includes perturbations, which help train reactive balance responses. Furthermore, it is hypothesised that improvements in gait quality through SDTT can enhance gait self-efficacy, which may mediate or moderate the transfer of training effects to everyday mobility. Understanding these mechanisms is essential for personalising interventions and maximising real-world outcomes.

ii. Objectives

The objectives of the StepuP project are to:

1. Understand the kinematic and neural mechanisms that underlie improvements in gait due to treadmill training with and without mechanically and VR-triggered gait adaptations in people with PD.
2. Assess the extent to which gait improvements measured in the laboratory transfer to improvements in daily-life mobility.
3. Identify the mechanisms that support or limit the transfer of training effects from lab-based gait improvements to real-world mobility.
4. Determine for whom treadmill training improves gait characteristics in the lab and for whom it does not, and similarly, who benefits in terms of daily-life mobility.

Achieving these objectives will advance understanding of the variability in individual response to treadmill training, allowing more targeted and ultimately personalised interventions to improve outcomes in PD.

iii. Endpoints This trial will evaluate the effects of treadmill training with and without perturbations on gait performance and neural correlates in people with PD.

Primary endpoint:

> Change in gait speed under controlled treadmill conditions.

Secondary endpoints:

• Clinical outcomes: Changes in motor symptoms and function measured through clinical assessments.
• Kinematic outcomes: Changes in gait parameters such as step length and variability from baseline to follow-up.
• Neurophysiological outcomes: EEG and EMG markers, including changes in EEG beta power and EEG-EMG coherence.

Exploratory endpoints:

• Real-world gait metrics assessed via wearable sensors.
• Gait self-efficacy assessed with validated questionnaires to examine psychological influences on transfer.

These outcomes will help identify how and for whom treadmill training leads to meaningful, lasting improvements in mobility.

• Study Type: Interventional
• Enrollment (Estimated): 42
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Matthew A Brodie, PhD; Phone Number: +614 4988 6272; Email: a.m.brodie@unsw.edu.au
• Study Contact Backup: Name: Yoshiro Okubo, PhD; Phone Number: +61 293991065; Email: y.okubo@neura.edu.au

Study Locations

• Australia
  • New South Wales
    • Randwick, New South Wales, Australia, 2031
      • Recruiting
      • Neuroscience Research Australia
      • Contact: Matthew A Brodie, PhD; Phone Number: +61 449 886 272; Email: a.m.brodie@unsw.edu.au
      • Contact: Yoshiro Okubo, PhD; Phone Number: 1065 +61 293991065; Email: y.okubo@neura.edu.au

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

1. Diagnosis of PD according to the MDS Criteria
2. Hoehn and Yahr stages I to III;
3. Movement Disorder Society-sponsored version of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) gait sub-score of 1 or more
4. Signed informed consent to participation

Exclusion Criteria:

• Any known general health condition likely to interfere with or to pose a contraindication to non-medically supervised physical exercise.
• Moderate or severe depression (BDI-II ≥18)
• Cognitive impairment which may preclude the possibility to provide a fully informed consent to enrolment.
• Linguistic comprehension capacity less than 75% in ordinary conversation
• Severe psychiatric comorbidity which may interfere with compliance to the study protocol
• History of or current status of substance dependency
• Unable to walk less than 1 floor
• Thoracic pain in the last 4 weeks
• Currently enrolled in other interventional studies
• Implanted Deep Brain Stimulation device

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Speed-dependent treadmill training (SDTT); SDTT adjusts the treadmill's speed in real time to match an individual's walking pace, creating a dynamic and adaptive training environment. This approach simulates real-world walking conditions, promoting neuromuscular coordination, balance, and functional mobility. By tailoring speed to the user's natural gait, SDTT supports the development of efficient and more natural walking patterns. It has shown promise across clinical populations, including those with neurological disorders, musculoskeletal conditions, or recovering from injury. Its flexibility allows for progressive challenge as walking ability improves, making SDTT a valuable tool for optimising gait and mobility outcomes.	Other: Exercise; SDTT adjusts the treadmill's speed in real time to match an individual's walking pace, creating a dynamic and adaptive training environment. This approach simulates real-world walking conditions, promoting neuromuscular coordination, balance, and functional mobility. By tailoring speed to the user's natural gait, SDTT supports the development of efficient and more natural walking patterns. It has shown promise across clinical populations, including those with neurological disorders, musculoskeletal conditions, or recovering from injury. Its flexibility allows for progressive challenge as walking ability improves, making SDTT a valuable tool for optimising gait and mobility outcomes.; Other Names: Treadmill training; Gait training; SDTT; Other: Exercise; The SDTT+ program combines speed-dependent treadmill training with perturbations and VR-triggered adaptations. Reactive gait responses are elicited through controlled accelerations and decelerations of treadmill belts, simulating real-life balance challenges.; Other Names: VR; Treadmill training; Gait training; SDTT+; perturbation training
Experimental: SDTT+ perturbations + VR triggered adaptations; The SDTT+ program combines speed-dependent treadmill training with perturbations and VR-triggered adaptations. Reactive gait responses are elicited through controlled accelerations and decelerations of treadmill belts, simulating real-life balance challenges.	Other: Exercise; SDTT adjusts the treadmill's speed in real time to match an individual's walking pace, creating a dynamic and adaptive training environment. This approach simulates real-world walking conditions, promoting neuromuscular coordination, balance, and functional mobility. By tailoring speed to the user's natural gait, SDTT supports the development of efficient and more natural walking patterns. It has shown promise across clinical populations, including those with neurological disorders, musculoskeletal conditions, or recovering from injury. Its flexibility allows for progressive challenge as walking ability improves, making SDTT a valuable tool for optimising gait and mobility outcomes.; Other Names: Treadmill training; Gait training; SDTT; Other: Exercise; The SDTT+ program combines speed-dependent treadmill training with perturbations and VR-triggered adaptations. Reactive gait responses are elicited through controlled accelerations and decelerations of treadmill belts, simulating real-life balance challenges.; Other Names: VR; Treadmill training; Gait training; SDTT+; perturbation training

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gait speed	Comfortable walking speed overground	Baseline (week 1), Post-Training (week 14), Follow-up (week 26)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fall Events	The number of falls experienced and whether they resulted in injury will be recorded. This includes a 12-month retrospective report at baseline and ongoing reporting throughout the study.	Retrospective report at Baseline (week 1); ongoing reporting through Follow-up (week 26).
EuroQol 5-Dimension (EQ-5D) Questionnaire	This quality-of-life instrument includes a descriptive profile and a visual analogue scale (VAS) to rate current health. The VAS ranges from 0 (the worst health imaginable) to 100 (the best health imaginable). Higher scores on the VAS indicate better health status.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
Frailty Index (FI)	The Frailty Index assesses physical frailty based on five criteria: shrinking (unintentional weight loss), low physical endurance or energy (self-reported exhaustion), low physical activity, weakness (grip strength), and slow walking speed. Based on the number of criteria met (0 to 5), participants are classified into the following categories: Non-frail (0 criteria met) Pre-frail (1-2 criteria met) Frail (3 or more criteria met)	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
FACIT Fatigue Scale (Functional Assessment of Chronic Illness Therapy - Fatigue)	The FACIT Fatigue Scale measures self-reported fatigue and its impact on daily activities and functioning over the past week. Each item is scored on a 5-point Likert scale ranging from 0 ("Not at all") to 4 ("Very much"). Total Score Range: 0 to 52. Higher scores indicate less fatigue and better functioning.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
Visual Analogue Scale (VAS)	The VAS is used to assess subjective pain intensity or other symptom severity.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
Foot placement kinematics	Three-dimensional motion capture will be used to evaluate gait and movement patterns, specicially the foot placement in relation to the centre of mass.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
Timed Up and Go (TUG)	The TUG test assesses mobility, balance, and walking ability.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
Two-Minute Walk Test (2MWT)	This test measures functional exercise capacity by recording the distance walked in two minutes.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
Mini-BESTest	The Mini-BESTest evaluates dynamic balance across multiple domains of postural control.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
Modified Gait Efficacy Scale (mGES)	The mGES measures confidence in walking under challenging everyday conditions.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
Short Falls Efficacy Scale International (Short FES-I)	The Short Falls Efficacy Scale International is a 7-item questionnaire assessing concern about falling during a range of physical and social activities. Each item is scored from 1 (not at all concerned) to 4 (very concerned), resulting in a total score ranging from 7 to 28. Higher scores indicate greater concern about falling, which reflects a worse outcome.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
Montreal Cognitive Assessment (MoCA)	The MoCA evaluates cognitive function, including memory, attention, language, and executive functions. The MoCA consists of 30 points, with scores ranging from 0 to 30. Higher scores indicate better cognitive function, reflecting a better outcome.	Baseline (week 1), Follow-up (week 26).
Color Trail Test (CTT)	The CTT assesses cognitive flexibility, visual attention, and processing speed. The CTT consists of two parts (CTT-1 and CTT-2), where participants are required to connect numbered circles in sequence, alternating between colours in the second part. Performance is measured by the time (in seconds) taken to complete each part. shorter completion times indicate better cognitive function, reflecting a better outcome.	Baseline (week 1), Follow-up (week 26).
Movement Disorder Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS Part III)	The MDS-UPDRS Part III is the motor examination component of the Unified Parkinson's Disease Rating Scale developed by the Movement Disorder Society. It assesses motor signs of Parkinson's disease across 18 items (e.g., tremor, rigidity, bradykinesia, posture, gait), each rated on a 5-point scale from 0 (normal) to 4 (severe impairment). The total score ranges from 0 to 132. Higher scores indicate greater motor impairment, reflecting a worse outcome.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
New Freezing of Gait Questionnaire (NFOGQ)	The NFOGQ is a 9-item patient-reported instrument designed to assess the presence, severity, and impact of freezing of gait (FOG) in individuals with Parkinson's disease. Items are scored on a 5-point Likert scale ranging from 0 (absence or no impact) to 4 (severe or frequent impact). The total score ranges from 0 to 28, with higher scores reflecting more severe and frequent freezing episodes. Higher scores indicate worse freezing of gait symptoms, representing a worse outcome.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
Daily Step Count	The average number of steps taken per day will be recorded via wearable sensors.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
Uninterrupted Walking Duration	Duration of uninterrupted walking bouts will be measured using wearable sensors.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
Stride Time Variability	Stride-to-stride variability in walking rhythm will be derived from sensor data.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
Gait Symmetry	The symmetry of gait parameters between left and right limbs will be calculated.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
System Usability Scale (SUS)	Participants' acceptability and satisfaction with the intervention will be assessed via the SUS. The SUS is a 10-item questionnaire that assesses user satisfaction and perceived usability of a system or intervention. Each item is rated on a 5-point Likert scale from 1 (strongly disagree) to 5 (strongly agree). Raw item scores are converted to a composite score ranging from 0 to 100. Higher scores indicate better perceived usability and greater user satisfaction, reflecting a better outcome.	Post-Training (week 14), Follow-up (week 26).
Physical Activity Enjoyment Scale (PACES)	Participants' acceptability and satisfaction with the intervention will be assessed via the PACES. The PACES is an 18-item questionnaire designed to assess enjoyment of physical activity. Each item is rated on a 7-point Likert scale (e.g., from "I enjoy it" to "I hate it"), with some items reverse-scored. The total score ranges from 18 to 126, with higher scores indicating greater enjoyment of physical activity, reflecting a better outcome.	Post-Training (week 14), Follow-up (week 26).
Attitudes Towards Physical Activity	The Exercise Self-Efficacy Scale (ESES) will assess changes in attitudes toward physical activity. The ESES is a 10-item questionnaire that assesses confidence in engaging in physical activity despite common barriers. Each item is rated from 1 (not at all confident) to 4 (always confident). Total scores range from 10 to 40. Higher scores indicate greater confidence in the ability to exercise, reflecting a better outcome.	Post-Training (week 14), Follow-up (week 26).
Participant experience	Semi-structured qualitative interviews will explore participant experiences, perceived barriers, enablers, and reasons for withdrawal. As this is a qualitative assessment, no numerical scale applies, and responses will be analysed using thematic analysis methods.	Post-Training (week 14), Follow-up (week 26).
Beta band activity	EEG (electroencephalogram) will be used to measure brain activity by recording electrical signals from the scalp. It will assess beta band activity during walking to examine changes in cortical involvement associated with gait and training.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
EEG-EMG coherency in the beta band	Coherency between EEG and EMG signals in the beta frequency band will be assessed during walking to evaluate changes in corticomuscular connectivity associated with gait and training.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fracture History	The number and type of fractures sustained in the 12 months prior to baseline will be recorded.	Baseline (week 1).
Changes in medication	All current medications (including antiparkinsonian and non-antiparkinsonian drugs) will be recorded at each study visit to monitor changes in use and assess potential side effects. Changes in medication will be categorised (e.g., dosage adjustments), and the number of participants with any change in medication will be reported.	Baseline (week 1), Post-Training (week 14), Follow-up (week 26).
Number of participants using mobility aids (indoors and outdoors)	The use of mobility aids (e.g., cane, walker, rollator) will be documented separately for indoor and outdoor environments. The number and percentage of participants using walking aids will be reported at each time point.	Baseline (week 1), Follow-up (week 26).
Hand Grip Strength	Grip strength will be assessed using a hand dynamometer as a proxy for overall strength and frailty.	Baseline (week 1).

Collaborators and Investigators

• Sponsor: The University of New South Wales
• Collaborators: IRCCS Azienda Ospedaliero-Universitaria di Bologna; Tel Aviv Medical Center; VU University of Amsterdam; Neuroscience Research Australia; Shake it up Australia Foundation
• Investigators: Study Chair: Matthew Brodie, PhD, University of New South Wales; Principal Investigator: Yoshiro Okubo, PhD, Neuroscience Research Australia, University of New South Wales; Principal Investigator: Daniel Chan, PhD, MD, University of New South Wales; Principal Investigator: Luca Modenese, PhD, University of New South Wales; Principal Investigator: Frederic von Wegner, PhD, MD, University of New South Wales; Principal Investigator: Phu Hoang, PhD, MD, Neuroscience Research Australia; Principal Investigator: Husna Razee, PhD, University of New South Wales; Principal Investigator: Paulo Silva Pelicioni, PhD, University of New South Wales; Principal Investigator: Vicki Miller, Shake it up Australia Foundation; Principal Investigator: Carolyn Sue, PhD, MD, Neuroscience Research Australia; Principal Investigator: Martin Ostrowski, PhD, University of New South Wales; Principal Investigator: Mayna Ratanapongleka, Neuroscience Research Australia

Study record dates

Study Major Dates

• Study Start (Actual): July 9, 2025
• Primary Completion (Estimated): September 30, 2026
• Study Completion (Estimated): November 30, 2026

Study Registration Dates

• First Submitted: May 19, 2025
• First Submitted That Met QC Criteria: July 6, 2025
• First Posted (Actual): July 9, 2025

Study Record Updates

• Last Update Posted (Actual): July 17, 2025
• Last Update Submitted That Met QC Criteria: July 13, 2025
• Last Verified: July 1, 2025

More Information

Terms related to this study

• Keywords: gait; falls; EMG; EEG; balance; wearable device; VR; perturbation; real-world gait
• Additional Relevant MeSH Terms: Synucleinopathies; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Movement Disorders; Parkinsonian Disorders; Basal Ganglia Diseases; Parkinson Disease
• Other Study ID Numbers: iRECS5114; 2022885 (Other Grant/Funding Number: The National Health and Medical Research Council)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: The pseudonymized personal dataset corresponding to study participants who have opted in at the time of consent
• IPD Sharing Time Frame: The pseudonymized personal dataset corresponding to study participants who have opted in at the time of consent will be made available within two years of study completion

IPD Sharing Access Criteria

Researchers comply with applicable data protection law, particularly Chapter V of the GDPR and the recommendations of the European Data Protection Board.

Researchers submit an approved data management and intended use plan.

Researchers approved by all sites including the University of New South Wales Human Research Ethics Committee.

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No