Steps Against the Burden of Parkinson's Disease - RCT Kiel

Official title

Steps Against the Burden of Parkinson's Disease

Overview

Parkinson's disease (PD) affects over 10 million worldwide, causing unstable gait and falls in 70% of patients despite medication. This leads to confidence loss, isolation, fractures, and hospitalizations. Treadmill training, augmented by mechanical/virtual-reality triggers, has proven effective in enhancing gait and reducing falls. However, underlying treadmill training mechanisms are unclear. To personalize training, we'll explore how PD patients benefit and transfer effects to daily life. This trial is part of three parallel randomized controlled trials within the Steps Against the Burden of Parkinson's Disease (CT-IDs: 6ef2e427b002, 6ef2e427b003, 6ef2e427b004) project, which will perform a pooled analysis across all sites in addition to individual RCT analyses. Each trial adheres to a shared core protocol while allowing for adaptations in the perturbation protocol, ensuring that data can be combined. Importantly, mechanistic findings and outcomes from this specific RCT will be reported independently, but also as part of a pooled analysis. In this trials, PD patients will undergo treadmill training with and without adaptations (perturbations). 12 sessions of treadmill training will be provided, with pre/post assessments and a Follow-up 12±2 weeks following T1 with pre/post assessments and a Follow-up 12±2 weeks following T1 at 8 to 12 weeks after the post assessment. For post treadmill training a phone app will be offered as a home-based speed dependent walk training intervention. This intervention is an App based training for gait adaptability and allows users to set their own training time and pace. It delivers a rhythmic metronomic beat for three different walking speeds, designed to trigger movement and encourage better walking patterns. Gait improvements are expected, driven by sensorimotor integration improving balance control. Biomechanical data analysis will reveal enhanced foot placement control. Neurophysiological changes will be studied through EEG and EMG, aiming to find improved gait stability with reduced EEG beta power and increased EEG-EMG coherence. Gait improvement in the lab might not correlate with daily-life results. Gait self-efficacy could influence transfer, prompting investigation into mechanistic associations with mobility outcomes. Remote digital tools will assess week-long mobility outcomes, employing machine learning to comprehend why some improve both in lab and life, while others don't. This will uncover mechanisms translating treatment effects into real-world outcomes, aiding personalized intervention development.

Detailed description

i. Rationale The rationale of this trial is that speed dependent treadmill training (SDTT) improves gait through improved sensorimotor integration, with changes in cortical activity as neural correlates. Additional benefits of treadmill training can be seen if perturbation or adaptations are added. This is based on the idea, that in addition to the sensorimotor integration the reactive balance in trained as well18. Furthermore, it hypothesizes that treadmill training and its effects on gait quality will improve gait self-efficacy, which mediates and/or modifies transfer of training effects to improved daily-life gait.

ii. Objectives

Thus, the objectives of our StepuP project are:

1. To 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. To assess to what extent improvements in gait due to treadmill training, as measured in the lab, transfer to improvements in daily life mobility; 3. To understand the mechanisms that underpin transfer from improvements in gait to improvements of mobility in daily life in people with PD; 4. To understand for whom treadmill training improves lab-based gait characteristics and for whom it does not, and understand for whom treadmill training improves mobility in daily life and for whom it does not.

Attaining these objectives will provide a better understanding of the successes and failures of treadmill training to improve gait stability and prevent falls in people with PD at an individual level, which in the medium term will allow targeted delivery of such interventions and in the long term will allow personalization of such interventions to improve outcomes for all.

iii. Endpoints Concerning the endpoints, this trial examines the effect of treadmill training with and without perturbations on gait performance, and neural correlates in people with PD. The primary endpoint is (change in) gait speed, secondary endpoints are divided into three groups (clinical, kinematic and neurophysiological). Clinical measures are used to assess the effect of training on disease symptoms. Kinematic measures are changes from baseline to Follow-up 12±2 weeks following T1, all under controlled conditions (treadmill), and provide insight into gait performance and quality. Neurophysiological measures aim to understand the neural control mechanisms underlying the training effects. On an exploratory level, the study aims to assess the training effects on daily-life gait by using wearable devices and assess gait self-efficacy using previously validated questionnaires.

Interventions

• Other Speed-dependent treadmill training (SDTT)
  This training methodology focuses on adjusting the treadmill's speed according to the individual's walking pace, creating a more dynamic and adaptive exercise environment. SDTT is designed to mimic real-world walking conditions and challenges, promoting neuromuscular coordination, balance, and overall mobility. By tailoring the treadmill speed to match the user's gait, SDTT encourages the development of natural and efficient walking patterns. This training technique has shown promise in various
• Other SDTT+ anteroposterior perturbations
  The SDTT+ anteroposterior perturbations program will trigger reactive gait adaptations by accelerations and decelerations of one of the belts of a split-belt treadmill.

Primary outcome measures

• Gait speed - T0 [Time frame: Baseline]
• Gait speed - T1 [Time frame: After Intervention (2-12 weeks)]
• Gait speed - T2 [Time frame: After Follow-up 12±2 weeks following T1 (20-32 weeks)]

Secondary outcome measures (12)

• Fall events (occurrence and frequency) and fall related injuries - T0 [Time frame: Baseline (T0)]
• Fracture history - T0 [Time frame: Baseline (T0)]
• Medication - T0 [Time frame: Baseline (T0)]
• Medication - T1 [Time frame: After Intervention (2-12 weeks)]
• Medication - T2 [Time frame: Follow-up 12±2 weeks following T1]
• Euro-Quality of life (EQ-5D) - T0 [Time frame: Baseline (T0)]
• Euro-Quality of life (EQ-5D) - T1 [Time frame: After Intervention (2-12 weeks)]
• Euro-Quality of life (EQ-5D) - T2 [Time frame: Follow-up 12±2 weeks following T1]
• Frailty Index (FI) - T0 [Time frame: Baseline (T0)]
• Frailty Index (FI) - T1 [Time frame: After Intervention (2-12 weeks)]
• Frailty Index (FI) - T2 [Time frame: Follow-up 12±2 weeks following T1]
• Functional Assessment of Chronic Illness Therapy (FACIT) Fatigue scale - T0 [Time frame: Baseline (T0)]

Eligibility criteria

Inclusion criteria

• Diagnosis of PD according to the MDS Criteria
• Hoehn and Yahr stages I to III;
• Movement Disorder Society-sponsored version of the Unified Parkinson Disease Rating Scale (MDS-UPDRS) gait sub-score of 1 or more
• 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

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Basic science

Study locations

Germany · 1 center

• University of Kiel — Kiel

Identifiers

NCT: NCT07058285 · 6ef2e427b002

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗