Transcutaneous Vagus Nerve Stimulation for Motor Recovery After Stroke

Study Overview
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Brief Summary
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This study will evaluate the safety and effectiveness of Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) for improving motor recovery after stroke. Subacute stroke patients will receive RAVANS or sham stimulation concurrent with arm motor training during 10 intervention sessions occurring daily for 30 minutes over 2 weeks. The safety and improvements in arm motor function after the intervention will be compared in patients receiving RAVANS to those receiving sham stimulation.

Detailed Description
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This study will evaluate the safety, feasibility and effectiveness of Respiratory-gated Auricular Vagal Afferent Nerve Stimulation (RAVANS) for improving motor recovery after stroke. Subacute stroke patients will be randomized to RAVANS or sham stimulation groups. Patients will receive RAVANS or sham stimulation concurrent with arm motor training during 10 sessions occurring daily for 30 minutes over 2 weeks. Safety will be compared in patients receiving RAVANS to those receiving sham stimulation. Feasibility will be evaluated by recruitment into the study and retention of enrolled patients. Changes in arm motor function will be compared between RAVANS and sham stimulation groups from baseline to immediately after the intervention period and to function at 3-months after stroke.

Official Title
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Safety and Effectiveness of Transcutaneous Vagus Nerve Stimulation Therapy to Improve Motor Recovery After Stroke

Conditions
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Stroke, Upper Extremity Paresis

Intervention / Treatment
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* Device: Active RAVANS concurrent with arm motor training
* Device: Inactive RAVANS concurrent with arm motor training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Supratentorial ischemic or hemorrhagic stroke incurred 4-30 days prior; Contralesional UL motor impairment defined by NIHSS item 5 score 1 or 2 (scale 0-4); Age ≥ 18; Able to provide written informed consent. Exclusion Criteria: Implanted electronic device (e.g., pacemaker, neurostimulator); Pregnancy; Major psychiatric or medical condition that could interfere with study participation; Medical condition affecting left ear that could interfere with delivering RAVANS (e.g., wound, infection, malignancy, hypoesthesia); Significant pre-existing disability of stroke-affected UL in activities of daily living due to prior stroke or other medical cause defined by Stroke Impact Scale item 7 (SIS-hand) mean score < 4 (scale: 0-5); History of seizure during year before stroke or > 1 post-stroke seizure; Significant cognitive or language impairment that would interfere with informed consent or study participation; Severe dysphagia; Bradycardia defined as resting heart rate < 50 bpm; Nonsustained ventricular tachycardia; Cardiac conduction disorder (i.e., bundle branch block, heart block, long Q-T syndrome); History of asystole; History of recurrent vaso-vagal syncope; Hypotension defined as blood pressure < 90/60 mmHg.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: RAVANS<br> | Device: Active RAVANS concurrent with arm motor training<br>* Patient receives non-painful, sensory-level stimulation to the skin of left outer ear, where nerve endings of the auricular branch of the vagus nerve reside, while participating in arm motor training<br>|
| Sham Comparator: Sham stimulation<br> | Device: Inactive RAVANS concurrent with arm motor training<br>* Patient does not receive stimulation delivered to the skin of left outer ear while participating in arm motor training<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Upper extremity motor impairment | Change in upper extremity subtest of Fugl Meyer Assessment (FMA-UE) score | Baseline to just after 10 intervention sessions, and baseline to 3 months post-stroke | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Upper extremity motor function | Change in Action Research Arm Test (ARAT) score | Baseline to just after 10 intervention sessions, and baseline to 3 months post-stroke | 
| Grip force control | Change in accuracy, variability and temporal structure of performance on a grip force control task | Baseline to just after 10 intervention sessions, and baseline to 3 months post-stroke | 
| Upper extremity disability | Change in hand subtest of Stroke Impact Scale (SIS-hand) score | Baseline to 3 months post-stroke | 
| Mood state, anxiety and depression | Change in Hospital Anxiety and Depression Scale (HADS) scores | Baseline to 3 months post-stroke | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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stroke, vagus nerve stimulation, upper extremity paresis