Association of VAgus Nerve Stimulation and Treadmill Training for GAit Rehabilitation in DE Novo Parkinson's Disease (AVANTGARDE-PD)
试验速览
- 阶段
- 不适用
- 状态
- 招募中
- 入组人数
- 60
- 试验地点
- 1
- 主要终点
- Evaluation of objective changes in gait speed (m/s) through gait analysis.
研究概览
简要总结
The goal of this clinical trial is to learn if transcutaneous auricular vagus nerve stimulation (taVNS) can improve gait and brain function in people with diagnosis of idiopathic Parkinson's disease (PD) within 6 months. It will also help researchers learn about the safety and biological effects of taVNS when used together with physical therapy.
The main questions it aims to answer are:
- Does taVNS paired with physical therapy improve walking speed and gait performance in people with PD?
- Does taVNS change brain activity or breain perfusion related to movement?
- Does taVNS reduce markers of inflammation and neurodegeneration in blood and saliva? Researchers will compare active taVNS to sham (placebo) stimulation to see if active taVNS works better when paired with physical therapy.
Participants will:
- Attend 12 rehabilitation sessions over 4 weeks (three per week)
- Receive either active or sham taVNS during each session while doing treadmill and conventional physical therapy
- Undergo gait and cognitive testing, MRI scans, and blood and saliva collection before and after treatment
- Return for a follow-up visit four weeks after therapy to check how long the effects last
详细描述
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.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Double (Participant, Outcomes Assessor)
入排标准
- 年龄范围
- 50 Years 至 80 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Idiopathic PD diagnosis within 6 months, confirmed by neurologist specialized in Parkinson's disease and movement disorders;
- •Ability to walking independently for at least 10 meters unassisted;
- •Age included between 50 and 80;
- •MMSE > 24;
- •On stable therapy for at least 1 month prior to the experiment.
排除标准
- •Clinical and radiological red flags for atypical, vascular parkinsonism or alternative diagnosis (e.g., normal pressure hydrocephalus);
- •Levodopa equivalent daily dose > 300 mg;
- •Any contraindication for taVNS (e.g., ear lesions, auditory prosthesis)
- •Any contraindication for MRI (e.g., non compatible pacemakers or prosthesis, claustrophobic subjects);
- •Concomitant neurological, orthopedic or active medical/oncological condition that would affect participating to the study;
- •Attempting to other neurorehabilitation programs within 3 months.
研究组 & 干预措施
taVNS paired with sensorized treadmill training (STT) and conventional physical therapy (cPT)
Participants will receive active taVNS, stimulation parameters: 25 Hz frequency, 200 μs pulse width, and intensity adjusted to the individual's sensory threshold, delivered to the left auricular tragus for the duration of each session (~30 minutes). During stimulation, participants will perform treadmill walking on a sensorized treadmill system with simultaneous conventional physical therapy exercises focused on posture, balance, and gait re-education. Sessions will be delivered over a 4-week period, for a total of 10 sessions.
干预措施: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) (Procedure)
taVNS paired with sensorized treadmill training (STT) and conventional physical therapy (cPT)
Participants will receive active taVNS, stimulation parameters: 25 Hz frequency, 200 μs pulse width, and intensity adjusted to the individual's sensory threshold, delivered to the left auricular tragus for the duration of each session (~30 minutes). During stimulation, participants will perform treadmill walking on a sensorized treadmill system with simultaneous conventional physical therapy exercises focused on posture, balance, and gait re-education. Sessions will be delivered over a 4-week period, for a total of 10 sessions.
干预措施: Conventional Physical Therapy (cPT) (Other)
taVNS paired with sensorized treadmill training (STT) and conventional physical therapy (cPT)
Participants will receive active taVNS, stimulation parameters: 25 Hz frequency, 200 μs pulse width, and intensity adjusted to the individual's sensory threshold, delivered to the left auricular tragus for the duration of each session (~30 minutes). During stimulation, participants will perform treadmill walking on a sensorized treadmill system with simultaneous conventional physical therapy exercises focused on posture, balance, and gait re-education. Sessions will be delivered over a 4-week period, for a total of 10 sessions.
干预措施: Sensorized Treadmill Training (STT) (Other)
taVNS paired with conventional physical therapy (cPT)
Participants will receive active taVNS (same parameters and device as Arm 1) during conventional physical therapy sessions without treadmill training.
Sessions will be delivered over a 4-week period, for a total of 10 sessions.
干预措施: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) (Procedure)
taVNS paired with conventional physical therapy (cPT)
Participants will receive active taVNS (same parameters and device as Arm 1) during conventional physical therapy sessions without treadmill training.
Sessions will be delivered over a 4-week period, for a total of 10 sessions.
干预措施: Conventional Physical Therapy (cPT) (Other)
Sham taVNS paired with STT and cPT
Sham stimulation will consist of few impulses delivered at 25 Hz for a duration of 60'' before waning, creating the same initial sensation without continuous current delivering.
Participants will simultaneously undergo treadmill-based and conventional physical therapy as described above.
Schedule: 10 sessions will be delivered over a 4-week period.
干预措施: Sham Transcutaneous Auricular Vagus Nerve Stimulation (Sham taVNS) (Procedure)
Sham taVNS paired with STT and cPT
Sham stimulation will consist of few impulses delivered at 25 Hz for a duration of 60'' before waning, creating the same initial sensation without continuous current delivering.
Participants will simultaneously undergo treadmill-based and conventional physical therapy as described above.
Schedule: 10 sessions will be delivered over a 4-week period.
干预措施: Conventional Physical Therapy (cPT) (Other)
Sham taVNS paired with STT and cPT
Sham stimulation will consist of few impulses delivered at 25 Hz for a duration of 60'' before waning, creating the same initial sensation without continuous current delivering.
Participants will simultaneously undergo treadmill-based and conventional physical therapy as described above.
Schedule: 10 sessions will be delivered over a 4-week period.
干预措施: Sensorized Treadmill Training (STT) (Other)
Sham taVNS paired with cPT
Participants will receive sham stimulation (same device and sham procedure as Arm 3) during conventional physical therapy sessions without treadmill training.
Schedule: 10 sessions will be delivered over a 4-week period.
干预措施: Sham Transcutaneous Auricular Vagus Nerve Stimulation (Sham taVNS) (Procedure)
Sham taVNS paired with cPT
Participants will receive sham stimulation (same device and sham procedure as Arm 3) during conventional physical therapy sessions without treadmill training.
Schedule: 10 sessions will be delivered over a 4-week period.
干预措施: Conventional Physical Therapy (cPT) (Other)
结局指标
主要结局
Evaluation of objective changes in gait speed (m/s) through gait analysis.
时间窗: Baseline (T0) and Post-intervention (T1, 4 weeks)
Gait speed (m/s) is measured using a 3D optoelectronic motion-capture system with inertial sensors during level walking on a 10-meter walkway with integrated force platforms. Standard lower-limb reflective markers and surface EMG are used to capture kinematic and muscle-activation patterns. Average gait speed is calculated as the mean forward velocity.
次要结局
- Cognitive Function (MoCA Total Score) assessment(Baseline (T0) and Post-intervention at 4 weeks (T1))
- Change in Cognitive Function (MoCA Total Score) from Post-intervention to Follow-up(Post-intervention at 4 weeks (T1) and Follow-up at 8 weeks (T2))
- Change in Motor Function (MDS-UPDRS Part III Total Score).(Baseline (T0) and Post-intervention at 4 weeks (T1).)
- Change in Gait Speed from Post-intervention to Follow-up.(Post-intervention at 4 weeks (T1) and Follow-up at 8 weeks (T2))
- Spatiotemporal and Kinematic Gait Parameters assessment (gait quality parameter).(Baseline (T0), Post-intervention at 4 weeks (T1))
- Cognitive Function (RBANS Total Score) assessment.(Baseline (T0) and Post-intervention at 4 weeks (T1))
- Quality of Life (PDQ-39 Total and Domain Scores) assessment.(Baseline (T0) and Post-intervention at 4 weeks (T1))
- Change in Cognitive Function (RBANS Total Score) from Post-intervention to Follow-up.(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.(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.(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.(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.(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.(Post-intervention at 4 weeks (T1) and Follow-up at 8 weeks (T2))
研究者
Massimo Marano
Principal Investigator
Fondazione Policlinico Universitario Campus Bio-Medico