Association of VAgus Nerve Stimulation and Treadmill Training for GAit Rehabilitation in DE Novo Parkinson's Disease

Parkinson's disease (PD) is characterized by gait disturbance, impaired mobility, and progressive involvement of neural circuits responsible for locomotion and postural control. Although physical therapy is effective, its benefits are often modest and short-lived. Transcutaneous auricular vagus nerve stimulation (taVNS) is a non-invasive neuromodulation technique that activates the auricular branch of the vagus nerve and engages ascending brainstem pathways involved in motor control, arousal regulation, and inflammatory modulation. Previous studies have shown that taVNS can influence subcortical β-band oscillations, improve gait parameters, enhance cognitive performance, and modulate systemic inflammatory markers in individuals with PD.

This randomized, double-blind, sham-controlled clinical trial evaluates whether pairing taVNS with gait-focused rehabilitation enhances motor outcomes and neural plasticity in individuals with de novo PD. Participants are newly diagnosed (≤6 months) and undergo a 4-week rehabilitation program consisting of conventional physiotherapy, with or without sensorized treadmill training. Active or sham taVNS is administered during each therapy session. The study includes four parallel arms to independently assess the contributions of taVNS and treadmill-based gait training.

Outcomes are assessed at baseline (T0), immediately post-intervention (T1), and at a 4-week follow-up visit (T2). Primary and secondary outcomes include quantitative gait parameters, clinical motor scales, cognitive performance, and quality-of-life measures. Exploratory outcomes include changes in cerebral blood flow measured with pseudo-continuous arterial spin labeling (PCASL), functional connectivity during a simulated gait task using fMRI, and blood and salivary biomarkers of inflammation and neurodegeneration (e.g., TNF-α, interleukins, and α-synuclein).

The study aims to determine whether taVNS enhances rehabilitation-induced improvements in gait, whether these benefits persist beyond the treatment period, and whether taVNS induces measurable changes in brain perfusion, functional networks, or circulating biological markers relevant to PD pathophysiology. Results may support the development of a scalable, non-invasive therapeutic approach that can be integrated into early PD management.

• Spatiotemporal and Kinematic Gait Parameters assessment (gait quality parameter). [Срок оценки: Baseline (T0), Post-intervention at 4 weeks (T1)]
• Change in Motor Function (MDS-UPDRS Part III Total Score). [Срок оценки: Baseline (T0) and Post-intervention at 4 weeks (T1).]
• Cognitive Function (MoCA Total Score) assessment [Срок оценки: Baseline (T0) and Post-intervention at 4 weeks (T1)]
• Quality of Life (PDQ-39 Total and Domain Scores) assessment. [Срок оценки: Baseline (T0) and Post-intervention at 4 weeks (T1)]
• Change in Gait Speed from Post-intervention to Follow-up. [Срок оценки: Post-intervention at 4 weeks (T1) and Follow-up at 8 weeks (T2)]
• Change in Spatiotemporal and Kinematic Gait Parameters (gait quality parameter) from Post-intervention to Follow-up. [Срок оценки: Post-intervention at 4 weeks (T1) and Follow-up at 8 weeks (T2)]
• Change in Motor Function (MDS-UPDRS Part III Total Score) from Post-intervention to Follow-up. [Срок оценки: Post-intervention at 4 weeks (T1) and Follow-up at 8 weeks (T2)]
• Change in Cognitive Function (MoCA Total Score) from Post-intervention to Follow-up [Срок оценки: Post-intervention at 4 weeks (T1) and Follow-up at 8 weeks (T2)]
• Change in Quality of Life (PDQ-39) from Post-intervention to Follow-up. [Срок оценки: Post-intervention at 4 weeks (T1) and Follow-up at 8 weeks (T2)]
• Change in Inflammatory Biomarkers (Serum and Salivary Cytokines) from Post-intervention to Follow-up. [Срок оценки: Post-intervention at 4 weeks (T1) and Follow-up at 8 weeks (T2)]
• Change in Neurodegenerative Biomarker Levels (α-Synuclein) from Post-intervention to Follow-up. [Срок оценки: Post-intervention at 4 weeks (T1) and Follow-up at 8 weeks (T2)]