Effects of Trans-Auricular Vagal Stimulation on Neuromotor Recovery in Subacute Stroke During Technological and Traditional Training

May 7, 2026 updated by: Istituti Clinici Scientifici Maugeri SpA

Effects of Trans-Auricular Vagal Stimulation on Neuromotor Recovery Post-Stroke in the Subacute Phase During Training With the Khymeia Technological Device and Traditional Rehabilitation

This randomized pilot clinical study aims to investigate the effects of trans-auricular vagus nerve stimulation (tVNS) on neuromotor recovery in patients in the subacute phase after stroke. Participants admitted for intensive rehabilitation at ICS Maugeri Centers (Montescano, Pavia, Nervi) will be randomized into four groups receiving either traditional or technological rehabilitation (Khymeia device), combined with active or sham tVNS.

The Parasym® device (CE 0197) delivers non-invasive stimulation of the auricular branch of the vagus nerve at the left ear for 60 minutes daily.

The primary outcome is the improvement in upper limb motor function, assessed by the Fugl-Meyer scale. Secondary outcomes include other clinical, cognitive, and psychological measures, as well as neurophysiological and cardiovascular autonomic parameters.

The study hypothesizes that coupling tVNS with rehabilitation enhances cortical plasticity and accelerates motor recovery. Adverse effects are expected to be minimal, with previous studies reporting only mild transient skin irritation. The results may provide new insights into the neurophysiological mechanisms of recovery and support the integration of non-invasive neuromodulation in post-stroke rehabilitation.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

48

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Locations

  • Italy
    • Pavia
      • Montescano, Pavia, Italy, 27040
        • Recruiting
        • ICS Maugeri - Montescano
        • Contact:
        • Sub-Investigator:
          • Weizhi Chen

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

Inclusion Criteria:

  • Patients with hemiplegia following ischemic or hemorrhagic stroke occurred within the previous 6 months, clinically stable
  • Age ≥ 18 years
  • Single cortical or subcortical lesion documented on neuroimaging, corresponding to the motor deficit
  • Cognitively able to understand and follow therapeutic instructions
  • Upper limb weakness confirmed by a Motricity Index score below maximum
  • Spasticity, if present, compatible with limb function (Modified Ashworth Scale ≤ 2)
  • Written informed consent provided

Exclusion Criteria:

  • Multiple brain lesions on neuroimaging
  • Severe spasticity (Modified Ashworth Scale 3-4)
  • Aphasia preventing comprehension of verbal instructions
  • Cognitive decline or behavioral disorders interfering with collaboration during training
  • Orthopedic conditions or surgical outcomes preventing the execution of the rehabilitation training

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Khymeia + Active tVNS
Device: Khymeia robotic upper limb rehabilitation
Robotic-assisted rehabilitation for the upper limbs using the Khymeia system.
Device: Active trans-auricular vagus nerve stimulation (tVNS)
Active tVNS with the Parasym® device (CE 0197). Electrode placed on the left tragus, 25 Hz, 250 μs, intensity to tolerance, 60 min/day, 5 days/week for 4 weeks.
Sham Comparator: Khymeia + Sham tVNS
Device: Sham tVNS
Sham tVNS using the Parasym® device with electrodes on the left earlobe (non-vagal area). Same schedule as active tVNS (60 min/day, 5 days/week for 4 weeks).
Device: Khymeia robotic upper limb rehabilitation
Robotic-assisted rehabilitation for the upper limbs using the Khymeia system.
Experimental: Traditional Rehabilitation + Active tVNS
Device: Active trans-auricular vagus nerve stimulation (tVNS)
Active tVNS with the Parasym® device (CE 0197). Electrode placed on the left tragus, 25 Hz, 250 μs, intensity to tolerance, 60 min/day, 5 days/week for 4 weeks.
Behavioral: Traditional Rehabilitation
Standard traditional physical therapy and rehabilitation protocols for upper limb recovery.
Sham Comparator: Traditional Rehabilitation + Sham tVNS
Device: Sham tVNS
Sham tVNS using the Parasym® device with electrodes on the left earlobe (non-vagal area). Same schedule as active tVNS (60 min/day, 5 days/week for 4 weeks).
Behavioral: Traditional Rehabilitation
Standard traditional physical therapy and rehabilitation protocols for upper limb recovery.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Upper limb motor recovery assessed by Fugl-Meyer Assessment (FMA-UE)
Time Frame: Baseline and 4 weeks after treatment
The FMA-UE is a scale used to measure sensorimotor impairment. Scores range from 0 to 66, where higher scores indicate better motor function.
Baseline and 4 weeks after treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Functional Independence Measure (FIM)
Time Frame: Baseline and 4 weeks.
The FIM assesses the physical and cognitive disability of a patient. Total scores range from 18 to 126, where higher scores indicate greater independence in activities of daily living.
Baseline and 4 weeks.
Barthel Index
Time Frame: Baseline and 4 weeks
The Barthel Index measures the extent to which a person can function independently and has mobility in activities of daily living (ADL). The total score ranges from 0 to 100, where higher scores indicate better performance and greater independence.
Baseline and 4 weeks
Frontal Assessment Battery (FAB)
Time Frame: Baseline and 4 weeks
The FAB is a brief tool to assess frontal lobe functions (executive functions). Total scores range from 0 to 18, where higher scores indicate better executive performance.
Baseline and 4 weeks
Patient Health Questionnaire-9 (PHQ-9)
Time Frame: Baseline and 4 weeks
The PHQ-9 is a multipurpose instrument for screening, monitoring, and measuring the severity of depression. Scores range from 0 to 27. Higher scores indicate worse outcome (greater severity of depressive symptoms)
Baseline and 4 weeks
Generalized Anxiety Disorder-7 (GAD-7)
Time Frame: Baseline and 4 weeks
The GAD-7 is a self-reported questionnaire for screening and severity measuring of generalized anxiety disorder. Scores range from 0 to 21. Higher scores indicate worse outcome (greater severity of anxiety symptoms).
Baseline and 4 weeks
Somatosensory Evoked Potentials (Median Nerve)
Time Frame: Baseline and 4 weeks
Evaluation of the N20 peak latency (measured in milliseconds) and/or the N20-P25 amplitude (measured in microvolts) of the Somatosensory Evoked Potentials following stimulation of the median nerve at the wrist. Lower latency values and higher amplitude values indicate better neurological conduction and somatosensory pathway integrity.
Baseline and 4 weeks
Mini-Mental State Examination (MMSE)
Time Frame: Baseline and 4 weeks
The MMSE is a 30-point questionnaire used to measure cognitive impairment. Scores range from 0 to 30, where higher scores indicate better cognitive function (scores ≥24 are typically considered normal).
Baseline and 4 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Istituti Clinici Scientifici Maugeri SpA

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

January 8, 2025

Primary Completion (Estimated)

December 20, 2026

Study Completion (Estimated)

April 3, 2027

Study Registration Dates

First Submitted

November 19, 2025

First Submitted That Met QC Criteria

November 19, 2025

First Posted (Actual)

November 28, 2025

Study Record Updates

Last Update Posted (Actual)

May 12, 2026

Last Update Submitted That Met QC Criteria

May 7, 2026

Last Verified

May 1, 2026

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 2665

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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