Effect of Transcutaneous Auricular Vagus Nerve Stimulation Combined With Upper Extremity Robot-Assisted Training on Upper Extremity Motor Functions in Stroke Patients

The effects of stroke on the upper extremity are a common and significant cause of long-term disability, with 65% of patients reporting an inability to participate in daily activities with the affected upper extremity after 6 months. Robotic-assisted training (RAT) has been widely used in recent years to improve upper extremity function. RAT positively impacts upper extremity function and activities of daily living by inducing motor learning from intense, highly repetitive, and task-focused movements of the upper extremity. However, current, limited clinical solutions, including minimally invasive transcutaneous auricular vagus nerve stimulation (taVNS), have not yielded promising results. Therefore, the aim of this study was to investigate the effects of the combination of taVNS and RTA on motor impairment, upper extremity motor function, grip strength, daily living characteristics, and quality of life in individuals with stroke. Stroke medications were randomly assigned to RDE+taVNS (n=15) and RDE+sham taVNS (n=15). All participants will receive conventional treatment for 45 minutes per day, 3 days per week, for 5 weeks. One group will also receive RDE+taVNS treatment for 45 minutes per day, 2 days per week, for 5 weeks, while the other group will receive RDE+sha taVNS. Participants will be assessed using the Fugl-Meyer Upper Extremity Assessment, ARAT (Action Research Arm Test), and Box and Block Test as primary outcomes at baseline and after 5 weeks.

This project will contribute to the literature by demonstrating the effectiveness of taVNS, one of the most promising methods available. Furthermore, the results will prompt discussion on the applicability of the method not only to stroke patients but also to other disease groups. The unique value of this project is that it is the first study to investigate product improvements in taVNS systems.

Study Overview

• Status: Recruiting
• Conditions: Stroke; Stroke Treatment
• Intervention / Treatment: Device: Robotics Assisted Education + taVNS; Other: Robotics Assisted Education + sham

• Study Type: Interventional
• Enrollment (Estimated): 30
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Yusuf Açıkgöz; Phone Number: +905396335531; Email: fztysfackgz@gmail.com
• Study Contact Backup: Name: Rüstem MUSTAFAOĞLU, associate professor; Phone Number: +905554178535; Email: rustem.mustafaoglu@iuc.edu.tr

Study Locations

• Turkey (Türkiye)
  • Istanbul
    • Istanbul, Istanbul, Turkey (Türkiye)
      • Recruiting
      • İstanbul Üniversitesi-Cerrahpaşa Sağlık Bilimleri Fakültesi Büyükçekmece Yerleşkesi
      • Contact: RÜSTEM MUSTAFAOĞLU; Phone Number: +90 555 417 8535; Email: rustem.mustafaoglu@iuc.edu.tr

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• 1) Individuals aged 18-70 years diagnosed with ischemic or hemorrhagic stroke lasting longer than 6 months,
• Moderate to severe upper extremity weakness (20-50 out of 66 on the Fugl-Meyer Upper Extremity Motor Assessment Scale),
• Ability to communicate and understand (Mini Mental State Examination (MMSE) score ≥ 23), and 4) Upper extremity spasticity of 2 or less on the Modified Ashworth Scale.

Exclusion Criteria:

• Use of any stimulation device, such as a pacemaker or other neurostimulator,
• Presence of a medical or cognitive condition (personality disorder, anxiety, depression, etc.) that would prevent participants from participating in the study,
• Receiving a Botox injection into the affected upper extremity at least 4 weeks prior,
• Severe spasticity in the upper extremity (Modified Ashworth Scale ≥3),
• Presence of dysphagia or aphasia,
• Presence of cardiac problems such as atrial fibrillation, atrial flutter, sick sinus syndrome, or atrioventricular block.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Robotics Assisted Education + taVNS	Device: Robotics Assisted Education + taVNS; Conventional rehabilitation will be administered 3 days a week, 45 minutes per day, for 5 weeks. The combination of Upper Extremity Robotic-Assisted Training and Transcutaneous Auricular Vagus Nerve Stimulation will be administered 2 days a week, 45 minutes per day, for 5 weeks.
Sham Comparator: Robotics Assisted Education + sham	Other: Robotics Assisted Education + sham; Conventional rehabilitation will be administered 3 days a week, 45 minutes per day, for 5 weeks. The combination of Upper Extremity Robotic-Assisted Training and Sham Transcutaneous Auricular Vagus Nerve Stimulation will be administered 2 days a week, 45 minutes per day, for 5 weeks.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Fugl Meyer Upper Extremity Evaluation (FM-UE)	We will use the Fugl-Meyer Upper Motor Assessment score, which is the most sensitive for treatment outcomes in stroke patients presenting with unilateral paresis in the post-stroke period. It measures upper extremity use and impairment, measuring shoulder, elbow, forearm, wrist, finger, and reflex movements from proximal to distal, synergistic to extrinsic. The score ranges from 0 to 66 and consists of 33 items. 0-28 indicates severe motor impairment; 29-42 indicates moderate motor impairment; and 43-66 indicates mild motor impairment. Higher scores indicate better performance. The FM-UE consists of one component, each rated on a 3-point ordinal scale (0=not achieved, 1=partially contributed, 2=completely contributed). The minimum clinically meaningful change on the FM-UE for chronic stroke has been determined to be 4.25 to 7.25. Consistent with the literature, we define an improvement of at least 6 points or more as significant.	Outcome measures will be assessed and recorded at baseline (assessment session) and after intervention (week 5).
Box and Block Test (BBT)	The Box and Block Test is a manual dexterity test used to assess upper extremity motor function. It primarily assesses gross motor function. It is calculated by the number of 2.5 cm3 blocks thrown from one side to the other in 1 minute. A box and block test kit has been prepared to meet international standards.	Outcome measures will be assessed and recorded at baseline (assessment session) and after intervention (week 5).

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stroke Impact Scale (SIS)	The SIS 3.0 assesses function and quality of life based on subjective report in eight clinically important domains. It consists of two parts. The first part is the main scale of the IAS, which assesses multidimensional health-related quality of life (QOL) including strength, hand function, ADL/instrumental ADL, mobility, communication, emotion, memory/thinking, and social participation. It consists of 59 items, and each item is subjectively rated by stroke patients on a 5-point Likert-type scale according to their perceived difficulty with the item in the past week. The score for each domain is converted to a score out of 100, and the average scores for all domains are used to represent stroke patients' multidimensional health-related quality of life. The formula Domain Score = [(Average Item Score -1) / (5 -1) x 100] is used to convert each domain score. SIS 3.0 also includes assessment of post-stroke recovery using a 0-100 visual analog scale (0: no recovery, 100: complete recovery)	Outcome measures will be assessed and recorded at baseline (assessment session) and after intervention (week 5).
Hand Grip Strength	Grip strength on the affected side will be measured with a Jamar Hydraulic Dynamometer. The measurement protocol will be explained and demonstrated to the participant by an experienced physiotherapist. The dynamometer grip size will be adjusted to the participant's hand size, and the participant will be asked to squeeze the dynamometer for a practice trial. Anti-gravity support will be provided to maintain the position if necessary. Grip strength measurements with the Jamar dynamometer have proven to be highly valid and reliable, and normative values have been published.	Outcome measures will be assessed and recorded at baseline (assessment session) and after intervention (week 5).

Collaborators and Investigators

• Sponsor: Istanbul University - Cerrahpasa
• Investigators: Principal Investigator: Rüstem Mustafaoğlu, associate professor, Istanbul University-Cerrahpasa Faculty of Health Sciences, Department of Physiotherapy and Rehabilitation; Study Chair: Fatih Aykut Çavdar, Marmara University, Faculty of Health Sciences, Department of Physiotherapy and Rehabilitation; Study Chair: Yusuf Açıkgöz, Istanbul University-Cerrahpasa, Institute of Postgraduate Education; Study Chair: İpek Yeldan, Professor, Istanbul University-Cerrahpasa Faculty of Health Sciences, Department of Physiotherapy and Rehabilitation; Study Director: Belgin Erhan, Professor, Istanbul Medeniyet University Faculty of Medicine, Department of International Medicine and Rehabilitation

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2025
• Primary Completion (Estimated): March 1, 2027
• Study Completion (Estimated): June 1, 2027

Study Registration Dates

• First Submitted: November 21, 2025
• First Submitted That Met QC Criteria: November 21, 2025
• First Posted (Actual): December 2, 2025

Study Record Updates

• Last Update Posted (Actual): December 2, 2025
• Last Update Submitted That Met QC Criteria: November 21, 2025
• Last Verified: September 1, 2025

More Information

Terms related to this study

• Keywords: Stroke; Transcutaneous Auricular Vagus Nerve Stimulation; taVNS; Upper Extremity Robot-Assisted Training
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke; salicylhydroxamic acid
• Other Study ID Numbers: 1277364

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No