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

NCT07337226 | Not Yet Recruiting

• 1 other identifier: AVANTGARDE-PD
• Study Type: interventional
• Target: 60
• Locations: 0 countries
• Sites: N/A

Brief Summary

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

Conditions

Idiopathic Parkinson's Disease (PD)

Keywords

Parkinson's disease; Vagus nerve stimulation; non invasive brain stimulation; treadmill training; freezing of gait; rehabilitation

Outcome Measures

Primary Outcomes (1)

• Evaluation of objective changes in gait speed (m/s) through gait analysis.

  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.

  Baseline (T0) and Post-intervention (T1, 4 weeks)

Secondary Outcomes (11)

• Spatiotemporal and Kinematic Gait Parameters assessment (gait quality parameter).

  Baseline (T0), Post-intervention at 4 weeks (T1)

• Change in Motor Function (MDS-UPDRS Part III Total Score).

  Baseline (T0) and 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 Gait Speed from Post-intervention to Follow-up.

  Post-intervention at 4 weeks (T1) and Follow-up at 8 weeks (T2)

Other Outcomes (4)

• Imaging Outcomes (PCASL).

  Baseline (T0) and Post-treatment at 4 weeks (T1)

• Imaging Outcomes (fMRI).

  Baseline (T0) and Post-treatment at 4 weeks (T1)

• Inflammatory Biomarkers (Serum and Salivary Cytokines)

  Baseline (T0) and Post-treatment at 4 weeks (T1)

Study Arms (4)

taVNS paired with sensorized treadmill training (STT) and conventional physical therapy (cPT)

ACTIVE COMPARATOR

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 occur three times per week for four weeks (12 sessions total).

Procedure: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS); Other: Conventional Physical Therapy (cPT); Other: Sensorized Treadmill Training (STT)

taVNS paired with conventional physical therapy (cPT)

ACTIVE COMPARATOR

Participants will receive active taVNS (same parameters and device as Arm 1) during conventional physical therapy sessions without treadmill training. Sessions will occur three times per week for four weeks.

Procedure: Transcutaneous Auricular Vagus Nerve Stimulation (taVNS); Other: Conventional Physical Therapy (cPT)

Sham taVNS paired with STT and cPT

SHAM COMPARATOR

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: three sessions per week for four weeks.

Procedure: Sham Transcutaneous Auricular Vagus Nerve Stimulation (Sham taVNS); Other: Conventional Physical Therapy (cPT); Other: Sensorized Treadmill Training (STT)

Sham taVNS paired with cPT

SHAM COMPARATOR

Participants will receive sham stimulation (same device and sham procedure as Arm 3) during conventional physical therapy sessions without treadmill training. Schedule: three sessions per week for four weeks.

Procedure: Sham Transcutaneous Auricular Vagus Nerve Stimulation (Sham taVNS); Other: Conventional Physical Therapy (cPT)

Interventions

Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) PROCEDURE

Active taVNS delivered at the inner tragus of the left ear (25 Hz, 200 μs, intensity at sensory threshold)

Also known as: Transcutaneous Auricular Vagus Nerve Stimulation, taVNS, nVNS, tVNS, Transauricular Vagus Nerve Stimulation

taVNS paired with conventional physical therapy (cPT); taVNS paired with sensorized treadmill training (STT) and conventional physical therapy (cPT)

Sham Transcutaneous Auricular Vagus Nerve Stimulation (Sham taVNS) PROCEDURE

Sham taVNS using the electrode placement as active taVNS but without electrical stimulation beyond the initial sensation.

Also known as: Sham transcutaneous auricular vagus nerve stimulation, sham taVNS, sham

Sham taVNS paired with STT and cPT; Sham taVNS paired with cPT

Conventional Physical Therapy (cPT) OTHER

Conventional Physical Therapy delivered to all groups consist of exercises aimed at posture alignment, reduction of hypertone, balance improvement and overground gait training.

Also known as: Conventional Physical Therapy, cPT

Sham taVNS paired with STT and cPT; Sham taVNS paired with cPT; taVNS paired with conventional physical therapy (cPT); taVNS paired with sensorized treadmill training (STT) and conventional physical therapy (cPT)

Sensorized Treadmill Training (STT) OTHER

Sensorized Treadmill Training consist of a sensorized gait treadmill training with continuous visual feedback combined with dual cognitive tasks (e.g. repeat digits, repeat sequence of words, counting down the dates).

Also known as: Sensorized Treadmill Training, STT, treadmill, sensorized treadmill

Sham taVNS paired with STT and cPT; taVNS paired with sensorized treadmill training (STT) and conventional physical therapy (cPT)

Eligibility Criteria

• Age: 50 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Fondazione Policlinico Universitario Campus Bio-Medico: lead

MeSH Terms

Conditions

Parkinson Disease

Interventions

salicylhydroxamic acid; 2-cyclohexylidenhydrazo-4-phenyl-thiazole; Exercise Test

Condition Hierarchy (Ancestors)

Parkinsonian Disorders; Basal Ganglia Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Movement Disorders; Synucleinopathies; Neurodegenerative Diseases

Intervention Hierarchy (Ancestors)

Heart Function Tests; Diagnostic Techniques, Cardiovascular; Diagnostic Techniques and Procedures; Diagnosis; Respiratory Function Tests; Diagnostic Techniques, Respiratory System; Ergometry; Investigative Techniques

Study Officials

• Massimo Marano, MD, PhD

  Fondazione Policlinico Universitario Campus Bio-Medico, Via Alvaro del Portillo, 200, 00128 Roma, Italy

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Massimo Marano, MD, PhD

CONTACT

+39 3333488802; m.marano@policlinicocampus.it

Gaia Anzini, MD

CONTACT

+39 3662007406; gaia.anzini@unicampus.it

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: November 16, 2025
• First Posted: January 13, 2026
• Study Start: January 1, 2026
• Primary Completion (Estimated): October 1, 2027
• Study Completion (Estimated): October 1, 2027
• Last Updated: January 13, 2026

Record last verified: 2026-01

Data Sharing

• IPD Sharing: Will not share