Evaluation of Noninvasive Vagus Nerve Stimulation on Functional Status in Ischemic Stroke

Study Overview
=================
Brief Summary
-----------------
In this study, the effectiveness of vagus nerve stimulation in patients with right and left hemiparesis will be compared with each other and with the sham application.

Detailed Description
-----------------
This prospective study will include 80 participants with a diagnosis of ischemic stroke who meet the inclusion criteria. In addition to the conventional rehabilitation program, non-invasive vagus nerve stimulation will be applied to the participants through the left ear with the Vagustim™-Ear tens electrode. As a vagus stimulation protocol, 10 sessions, 30 minutes, noninvasive auricular stimulation will be applied, stimulation frequency is 10 Hz, the pulse width is 300 µs, biphasic. In the study, sham vagus nerve stimulation (0 mA) will be applied to the participants in the control group. The study will be completed when the evaluation of the participants is made in the 1st and 3rd months after the last intervention. The upper extremity functions of the patients participating in the study were determined by Fugl-Meyer upper extremity test and box and block test, upper and lower extremity spasticities by modified Ashworth scale, and sleep quality by Pittsburgh sleep quality index. Quality of life will be evaluated with the stroke-specific quality of life scale, balance functions with the Berg balance test, dependency levels in daily activities with the Barthel index, and sympathetic dysfunctions with COMPASS-31. Participants' blood pressure and pulse values will be evaluated before and after each session.

Official Title
-----------------
Evaluation of Noninvasive Vagus Nerve Stimulation on Functional Status in Ischemic Stroke

Conditions
-----------------
Stroke, Ischemic, Hemiplegia, Hemiparesis;Poststroke/CVA

Intervention / Treatment
-----------------
* Device: transcutaneous auricular vagus nerve stimulation
* Device: Sham stimulation


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: History of subacute-chronic ischemic stroke (3-12 months) Exclusion Criteria: Bilateral or unilateral previous injury to the vagus nerve (eg injury during carotid endarterectomy). Severe depression (Beck Depression Scale > 29) Current use of any other stimulation device, such as a pacemaker or other neurostimulator; current use of any other investigational device or drug. Medical or mental instability (diagnosis of personality disorder, psychosis, or substance abuse) that would prevent the subject from following the protocol timeline. Pregnancy or planning to become pregnant or breastfeed during the study period. Botox injections or hemiplegia rehabilitation within 6 months before treatment. Having a history of hemorrhagic stroke Presence of ongoing dysphagia or aspiration difficulties.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 65 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

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


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Active Stimulation for right hemiparesis patients<br>Active non-invasive transauricular vagus nerve stimulation over left ear in post-stroke right hemiparesis | Device: transcutaneous auricular vagus nerve stimulation<br>* In addition to the conventional rehabilitation program, non-invasive vagus nerve stimulation will be applied to the participants through the left ear with the Vagustim™-Ear tens electrode. As a vagus stimulation protocol, 10 sessions, 30 minutes, noninvasive auricular stimulation will be applied, stimulation frequency is 10 Hz, pulse width is 300 µs, and biphasic.<br>|
| Sham Comparator: Sham Stimulation for right hemiparesis patients<br>Sham non-invasive transauricular vagus nerve stimulation over left ear in post-stroke right hemiparesis | Device: Sham stimulation<br>* In addition to the conventional rehabilitation program, sham vagus nerve stimulation (0 mA) will be applied to the participants in the control group. Non-invasive vagus nerve stimulation will be applied to the participants through the left ear with the Vagustim™-Ear tens electrode. As a vagus stimulation protocol, 10 sessions, 30 minutes, and noninvasive auricular stimulation will be applied.<br>|
| Active Comparator: Active Stimulation for left hemiparesis patients<br>Active non-invasive transauricular vagus nerve stimulation over left ear in post-stroke left hemiparesis | Device: transcutaneous auricular vagus nerve stimulation<br>* In addition to the conventional rehabilitation program, non-invasive vagus nerve stimulation will be applied to the participants through the left ear with the Vagustim™-Ear tens electrode. As a vagus stimulation protocol, 10 sessions, 30 minutes, noninvasive auricular stimulation will be applied, stimulation frequency is 10 Hz, pulse width is 300 µs, and biphasic.<br>|
| Sham Comparator: Sham Stimulation for left hemiparesis patients<br>Sham non-invasive transauricular vagus nerve stimulation over left ear in post-stroke left hemiparesis | Device: Sham stimulation<br>* In addition to the conventional rehabilitation program, sham vagus nerve stimulation (0 mA) will be applied to the participants in the control group. Non-invasive vagus nerve stimulation will be applied to the participants through the left ear with the Vagustim™-Ear tens electrode. As a vagus stimulation protocol, 10 sessions, 30 minutes, and noninvasive auricular stimulation will be applied.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fugl-Meyer Assessment for Upper Extremity | It is considered as gold standard and is the only impairment level measure recommended for stroke trials. It consists of 30 items assessing motor function and 3 items assessing reflex function. The score most applicable to task performance is given from 0, inability, 1, beginning ability, to 2, normal (total score range, 0-66). | Change from Baseline Fugl-Meyer Assessment for Upper Extremity at 4 weeks and 12 weeks | 
| Stroke-Specific Quality of Life Scale | The Stroke-Specific Quality of Life Scale assesses health-related quality of life specific to stroke survivors. 49 questions under 12 subscales. Scores range from 49-245. Higher scores indicate better functioning. | Change from Baseline Stroke-Specific Quality of Life Scale at 4 weeks and 12 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Barthel Index | Barthel Index is used to measure the disability experienced by the patient in performing activities of daily living. It comprises 10 items regarding activities of daily living and mobility and assesses feeding, transfer from wheelchair to bed and back, self-care, bathing, walking, climbing stairs, dressing, and bladder and bowel continence. Scoring is based on whether the patient requires help or not in performing any of the above mentioned activities. Proposed guidelines for interpreting Barthel scores are that scores of 0-20 indicate total dependency, 21-60 indicate severe dependency, 61-90 indicate moderate dependency, and 91-99 indicates slight dependency. | Change from Baseline Barthel Index at 4 weeks and 12 weeks | 
| Modified Ashworth Scale | Modified Ashworth Scale (MAS) is used to assess spasticity. Scoring: 0: No increase in tone; 1: slight increase in tone giving a catch when slight increase in muscle tone, manifested by the limb was moved in flexion or extension; 1+: slight increase in muscle tone, manifested by a catch followed by minimal resistance throughout (ROM ); 2: more marked increase in tone but more marked increased in muscle tone through most limb easily flexed; 3: considerable increase in tone, passive movement difficult and, 4: limb rigid in flexion or extension | Change from Baseline Modified Ashworth Scale at 4 weeks and 12 weeks | 
| Berg Balance Test | Berg Balance Test is consisting of 14 items and measures the ability of individuals to maintain balance while performing functional tasks. Each task is scored from 0 (cannot perform independently) to 4 (stated best performance). 0-20 points are interpreted as high risk of falling, between 21-40 points as medium risk of falling, and between 41-56 points as low risk. | Change from Baseline Berg Balance Test at 4 weeks and 12 weeks | 
| Composite Autonomic Symptom Score (COMPASS-31) | The test has 6 domains looking at autonomic symptoms: orthostatic intolerance, vasomotor, secretomotor, gastrointestinal, bladder and pupillomotor. The six domain scores sum to a total COMPASS 31 score of 0 to 100, and a higher COMPASS 31 score indicates more severe autonomic symptoms. | Change from Baseline Composite Autonomic Symptom Score at 4 weeks and 12 weeks | 
| Pittsburgh Sleep Quality Index | The Pittsburgh Sleep Quality Index (PSQI) is a self-rated questionnaire which assesses sleep quality and disturbances over a 1-month time interval. Each item is weighted on a 0-3 interval scale. The global PSQI score is then calculated by totaling the seven component scores, providing an overall score ranging from 0 to 21, where lower scores denote a healthier sleep quality. | Change from Baseline Pittsburgh Sleep Quality Index at 4 weeks and 12 weeks |