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

NCT07254390 | Recruiting

• 1 other identifier: 2665
• Study Type: interventional
• Target: 48
• Locations: 1 country
• Sites: 1

Brief Summary

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.

Conditions

Stroke

Keywords

Transcutaneous vagus nerve stimulation (tVNS); Stroke rehabilitation; Neuroplasticity; Upper limb motor recovery; Non-invasive neuromodulation

Outcome Measures

Primary Outcomes (1)

• Upper limb motor recovery assessed by Fugl-Meyer Assessment (FMA-UE)

  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 Outcomes (7)

• Functional Independence Measure (FIM)

  Baseline and 4 weeks.

• Barthel Index

  Baseline and 4 weeks

• Mini-Mental State Examination (MMSE)

  Baseline and 4 weeks

• Frontal Assessment Battery (FAB)

  Baseline and 4 weeks

• Patient Health Questionnaire-9 (PHQ-9)

  Baseline and 4 weeks

Study Arms (4)

Khymeia + Sham tVNS

SHAM COMPARATOR

Device: Sham tVNS; Device: Khymeia robotic upper limb rehabilitation

Traditional Rehabilitation + Active tVNS

EXPERIMENTAL

Device: Active trans-auricular vagus nerve stimulation (tVNS); Behavioral: Traditional Rehabilitation

Traditional Rehabilitation + Sham tVNS

SHAM COMPARATOR

Device: Sham tVNS; Behavioral: Traditional Rehabilitation

Khymeia + Active tVNS

EXPERIMENTAL

Device: Active trans-auricular vagus nerve stimulation (tVNS); Device: Khymeia robotic upper limb rehabilitation

Interventions

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.

Khymeia + Active tVNS; Traditional Rehabilitation + Active tVNS

Khymeia robotic upper limb rehabilitation DEVICE

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

Khymeia + Active tVNS; Khymeia + Sham tVNS

Traditional Rehabilitation BEHAVIORAL

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

Traditional Rehabilitation + Active tVNS; Traditional Rehabilitation + Sham tVNS

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 + Sham tVNS; Traditional Rehabilitation + Sham tVNS

Eligibility Criteria

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

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Istituti Clinici Scientifici Maugeri SpA: lead

Study Sites (1)

ICS Maugeri - Montescano

Montescano, Pavia, 27040, Italy

RECRUITING

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Cira Fundaro'

CONTACT

0385247268; cira.fundaro@icsmaugeri.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: SPONSOR

Study Record Dates

• First Submitted: November 19, 2025
• First Posted: November 28, 2025
• Study Start: January 8, 2025
• Primary Completion (Estimated): December 20, 2026
• Study Completion (Estimated): April 3, 2027
• Last Updated: May 12, 2026

Record last verified: 2026-05

Locations

IT (1)