StrokeNCT07254390
Effects of Trans-Auricular Vagal Stimulation on Neuromotor Recovery in Subacute Stroke During Technological and Traditional Training
A study testing Active trans-auricular vagus nerve stimulation (tVNS), Khymeia robotic upper limb rehabilitation and Traditional Rehabilitation in people with Stroke, run by Istituti Clinici Scientifici Maugeri SpA at 1 site in Italy.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Stroke
- What is being tested?
- Active trans-auricular vagus nerve stimulation (tVNS), Khymeia robotic upper limb rehabilitation and Traditional Rehabilitation
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 48 participants
- Where
- 1 siteItaly
- Study dates
- 8 Jan 2025to 3 Apr 2027
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
Who cannot join
- 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
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Italy1 site, 1 recruiting
- Recruiting
ICS Maugeri - Montescano
Montescano, Pavia, 27040
Cira Fundarò, MD, 0385247268, cira.fundaro@icsmaugeri.it
Weizhi Chen
About this study
Official 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
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.
Read more
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
- Being tested
- Active trans-auricular vagus nerve stimulation (tVNS), Sham tVNS, Khymeia robotic upper limb rehabilitation, Traditional Rehabilitation
- Keywords
- Transcutaneous vagus nerve stimulation (tVNS), Stroke rehabilitation, Neuroplasticity, Upper limb motor recovery, Non-invasive neuromodulation
- Medical subject headings
- Stroke
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
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 tVNSDevice
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 rehabilitationDevice
Robotic-assisted rehabilitation for the upper limbs using the Khymeia system.
Traditional RehabilitationBehavioural
Standard traditional physical therapy and rehabilitation protocols for upper limb recovery.
| Study group | Role | What they receive |
|---|---|---|
| Khymeia + Sham tVNS | Sham comparator | Not described Receives: Device: Sham tVNS; Device: Khymeia robotic upper limb rehabilitation |
| Traditional Rehabilitation + Active tVNS | Experimental | Not described Receives: Device: Active trans-auricular vagus nerve stimulation (tVNS); Behavioral: Traditional Rehabilitation |
| Traditional Rehabilitation + Sham tVNS | Sham comparator | Not described Receives: Device: Sham tVNS; Behavioral: Traditional Rehabilitation |
| Khymeia + Active tVNS | Experimental | Not described Receives: Device: Active trans-auricular vagus nerve stimulation (tVNS); Device: Khymeia robotic upper limb rehabilitation |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Baseline and 4 weeks after treatment
Secondary outcomes (7)
Functional Independence Measure (FIM)
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.
Measured: Baseline and 4 weeks.
Barthel Index
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.
Measured: Baseline and 4 weeks
Mini-Mental State Examination (MMSE)
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).
Measured: Baseline and 4 weeks
Frontal Assessment Battery (FAB)
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.
Measured: Baseline and 4 weeks
Patient Health Questionnaire-9 (PHQ-9)
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)
Measured: Baseline and 4 weeks
Generalized Anxiety Disorder-7 (GAD-7)
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).
Measured: Baseline and 4 weeks
Somatosensory Evoked Potentials (Median Nerve)
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.
Measured: Baseline and 4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Nov 2025
- Study start8 Jan 2025
- Primary completion20 Dec 2026 (estimated)
- Study completion3 Apr 2027 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for StrokeStudies of the same condition, open and under way.
- More trials run by Istituti Clinici Scientifici Maugeri SpAThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind
- Who is masked
- Participant, Outcomes assessor
- Enrolment
- 48 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Istituti Clinici Scientifici Maugeri SpA
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07254390
- Sponsor's protocol ID
- 2665
- Status last verified
- May 2026
- First submitted
- 19 Nov 2025
- Last updated
- 12 May 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 12 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official 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
- ClinicalTrials.gov ID
- NCT07254390
- Acronym / sponsor ID
- 2665
- Conditions
- Stroke
- Keywords
- Transcutaneous vagus nerve stimulation (tVNS), Stroke rehabilitation, Neuroplasticity, Upper limb motor recovery, Non-invasive neuromodulation
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 48 participants (estimated)
- Lead sponsor
- Istituti Clinici Scientifici Maugeri SpAUniversity, hospital or other
- Study start
- 8 Jan 2025 (actual)
- Primary completion
- 20 Dec 2026 (estimated)
- Study completion
- 3 Apr 2027 (estimated)
- First posted
- 28 Nov 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Double blind (participant, outcomes assessor)
- Number of arms
- 4
| Arm | Type | Receives |
|---|---|---|
| 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- 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
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| 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. | Device | Khymeia + Active tVNS, Traditional Rehabilitation + Active tVNS |
| Sham tVNSSham 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 + Sham tVNS, Traditional Rehabilitation + Sham tVNS |
| Khymeia robotic upper limb rehabilitationRobotic-assisted rehabilitation for the upper limbs using the Khymeia system. | Device | Khymeia + Active tVNS, Khymeia + Sham tVNS |
| Traditional RehabilitationStandard traditional physical therapy and rehabilitation protocols for upper limb recovery. | Behavioural | Traditional Rehabilitation + Active tVNS, Traditional Rehabilitation + Sham tVNS |
Primary outcome
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.
7 secondary outcomes
Functional Independence Measure (FIM)
Time frame: Baseline and 4 weeks.
Barthel Index
Time frame: Baseline and 4 weeks
Mini-Mental State Examination (MMSE)
Time frame: Baseline and 4 weeks
Frontal Assessment Battery (FAB)
Time frame: Baseline and 4 weeks
Patient Health Questionnaire-9 (PHQ-9)
Time frame: Baseline and 4 weeks
Generalized Anxiety Disorder-7 (GAD-7)
Time frame: Baseline and 4 weeks
Somatosensory Evoked Potentials (Median Nerve)
Time frame: Baseline and 4 weeks
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 May 2026.
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Web-Based Tele-Rehabilitation Using Action Observation and Mirror Therapy for Subacute Stroke: A Randomized Controlled Trial
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Active trans-auricular vagus nerve stimulation (tVNS), Khymeia robotic upper limb rehabilitation and Traditional Rehabilitation in people with Stroke, run by Istituti Clinici Scientifici Maugeri SpA at 1 site in Italy.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: looking for participants now, as of the sponsor's last update on 12 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Italy. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Cira Fundaro' (0385247268, cira.fundaro@icsmaugeri.it), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Upper limb motor recovery assessed by Fugl-Meyer Assessment (FMA-UE) (time frame: Baseline and 4 weeks after treatment). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 May 2026.