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NCT Number: NCT07254390

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

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.

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Key information

Age range

18 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

ICS Maugeri - Montescano

Montescano, Pavia, 27040, Italy

Location status: Recruiting

Location contact

Cira Fundarò, MD

CONTACT

[email protected]

0385247268

Weizhi Chen

SUB_INVESTIGATOR

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Active trans-auricular vagus nerve stimulation (tVNS)

Device

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 tVNS

Device

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).

Khymeia robotic upper limb rehabilitation

Device

Robotic-assisted rehabilitation for the upper limbs using the Khymeia system.

Traditional Rehabilitation

Behavioral

Standard traditional physical therapy and rehabilitation protocols for upper limb recovery.

Primary outcomes

  1. 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.

Secondary outcomes

  1. 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.

  2. 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.

  3. 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).

  4. 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.

  5. 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)

  6. 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).

  7. 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.

Study contacts

Contact information is provided by the study sponsor or research team.

Cira Fundaro'

CONTACT

[email protected]

0385247268

Sponsors and collaborators

Lead sponsor

Istituti Clinici Scientifici Maugeri SpA

Other

Registry information

Official study title

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

Important dates

Study start
2025
Primary completion
2026
Study completion
2027
First posted
Nov 28, 2025
Registry last updated
May 12, 2026

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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