Comperative Effects of Transcutaneous Auricular and Cervical Vagus Nerve Stimulation in Subacute Stroke Patients

NCT ID: NCT07253870

Last Updated: 2025-12-03

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 54 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2025-11-20
• Study Completion Date: 2026-05-20

Brief Summary

This study aims to determine whether transcutaneous vagus nerve stimulation (tVNS) via auricular or cervical branches enhances recovery when combined with task-specific training in subacute stroke patients. We anticipate finding that both stimulation methods may improve upper limb motor function compared to conventional therapy. The research is expected to reveal specific cognitive domains (attention, memory, executive function) that benefit most from each stimulation approach, while also demonstrating meaningful improvements in patients' quality of life measures. These findings may make a significant practical contribution by providing clinicians with evidence-based guidance on suitable tVNS approach for improving functional independence and quality of life for stroke survivors.

Detailed Description

Stroke is characterized as a neurological deficit resulting from a sudden focal injury to central nervous system due to vascular issue by blockage and rupture of artery that leads to hypoxic injury and ultimately cell death. Stroke is primarily categories into two types: ischemic stroke that accounts for 85 % of cases and haemorrhagic stroke which make up 15%. Stroke leads to physical, cognitive, speech, perceptual and psychological Impairments. Post stroke impairments of the upper limb and lower limb leads to activity limitations in self-care and mobility and restricted participation in caring family and employment.

Multidisciplinary approach is used in stroke rehabilitation to create a rehabilitation program that aim to improve the function and improve the quality of life. Physical medicine and rehabilitation is focused on promoting recovery, improving or restoring functional abilities, anticipating potential long-term complications, and enhancing the quality of life for individuals with physical impairments or disabilities. Now a days there are many contemporary approaches used in rehabilitation like non-invasive brain simulation, robotics, gamification, virtual reality, CIMT, mirror therapy and many others, aimed to enhance the recovery after stroke.

Transcutaneous vagus nerve stimulation tVNS was developed two decades ago as a non-invasive, cost effective and easily applicable treatment option as compared to invasive vagus nerve stimulation for the treatment of epilepsy, cognitive impairments and stroke rehabilitation. Cutaneous innervation of vagus nerve is by two branches, one through auricular branch at external acoustic meatus, inner tragus, and the periauricular skin surrounding the cymba conchae and the other through cervical branch at anterior to sternocleidomastoid at the mid of neck. Several devices are used for stimulating the vagus nerve transcutaneously, as NEMOS that stimulates at the concha of outer ear, CE (European Conformity) and a hand held device Gammacore. On the other hand TENS-200 or Digitimer DS7A often require custom-made electrodes, also used in stimulation. In 2018 a systematic review was conducted on the safety of tVNS that results in transcutaneous vagus nerve stimulation (tVNS) is generally well tolerated in humans at the tested doses and is considered safe.

In parasympathetic nervous system vagus nerve is a major component that emerges from the medullae oblongata, passes through the jugular foramen to leave the cranial activity and travel downward between the neurovascular bundle situated between internal jugular vein and common carotid artery. It extends to thoracic and abdominal cavities and supply multiple organs and regulate autonomic nervous system. VNS play its role by stimulating the afferent and efferent fibers of the VN that primarily comprises the unmyelinated sensory afferent fibers, accounting for 80-90% of the nerve fiber, with the remaining 10-20% being myelinated efferent fibers. These fibers project upward to the brainstem nucleus and relay circuit, influencing the nucleus tractus solitarius (NTS) and locus coeruleus (LC). NTS projects different brain areas as amygdala, hippocampus, locus coeruleus and prefrontal cortex. The effects of direct VNS on enhancement of memory, motor learning and neuroplasticity also suggest a role for treatment of cognitive disorders, stroke, and other conditions. The cholinergic activity of the efferent branch of the vagus nerve has an immune inflammatory regulatory effect, which is referred to as the cholinergic anti-inflammatory pathway (CAP).

Upper limb impairment is a frequent outcome of stroke, greatly affecting a patient's quality of life. Recent research has shown that vagus nerve stimulation (VNS) combined with rehabilitation significantly enhances forelimb strength and movement speed in rat models of ischemic stroke. VNS is thought to amplify the advantages of rehabilitation by fostering neuroplasticity.

While the efficacy of taVNS in enhancing motor recovery post-stroke is well-documented, there is a paucity of comparative studies investigating the distinct effects of auricular and cervical tVNS on upper limb function, cognitive outcomes, and quality of life in subacute stroke patients. This gap necessitates further research to determine optimal stimulation modalities and their broader neurorehabilitation benefits

Conditions

Stroke; Stroke, Acute

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

Transcutaneous vagus nerve stimulation through auricular branch along with task specific exercises

Group A will receive application of TENS to stimulate the vagus nerve at the ear level, apply the clip electrodes at the targus/cymba concha and the other electrode anywhere in the skin over neck along with task specific exercises

Group Type: EXPERIMENTAL

Transcutaneous vagus nerve stimulation through auricular branch along with task specific exercises

Intervention Type: OTHER

Group A will receive application of TENS to stimulate the vagus nerve at the ear level, apply the clip electrodes at the targus/cymba concha and the other electrode anywhere in the skin over neck Mode on TENS will be normal, with the width pulse of 250µs. FITT will be as follow Frequency of 25 Hz, Intensity 1mA, Time 30 minutes and the treatment will be of 5 days a week for 8 consecutive weeks

• For grip and release: Use a soft ball, putty, or other textured objects. The patient squeezes the object to strengthen their grip and then releases it.
• Reaching task: Place objects at varying distances in front of the patient. Encourage them to reach out with the affected arm to grasp the items and then bring them back.
• Bilateral arm movement: Encourage simultaneous reaching or moving with both arms (e.g., pushing against a wall or lifting a lightweight object) to promote symmetry and coordination. Improve coordination and function of both arms.
• Tabletop activities: Engaging in activities lik

Transcutaneous vagus nerve stimulation through cervical branch along with task specific exercises

Group B will receive application of TENS to stimulate the vagus nerve at the neck level, apply the pad electrodes at the anterior mid to neck and the other electrode over back of neck along task specific exercises

Group Type: ACTIVE_COMPARATOR

Transcutaneous vagus nerve stimulation through cervical branch along with task specific exercises

Intervention Type: OTHER

Group B will receive application of TENS to stimulate the vagus nerve at the neck level, apply the pad electrodes at the anterior mid to neck and the other electrode over back of neck Mode on TENS will be normal, with the width pulse of 250µs. FITT will be as follow Frequency of 25 Hz, Intensity 1mA, Time 30 minutes and the treatment will be of 5 days a week for 8 consecutive weeks

• For grip and release: Use a soft ball, putty, or other textured objects. The patient squeezes the object to strengthen their grip and then releases it.
• Reaching task: Place objects at varying distances in front of the patient. Encourage them to reach out with the affected arm to grasp the items and then bring them back.
• Bilateral arm movement: Encourage simultaneous reaching or moving with both arms (e.g., pushing against a wall or lifting a lightweight object) to promote symmetry and coordination. Improve coordination and function of both arms.
• Tabletop activities: Engaging in activities like sortin

Interventions

Transcutaneous vagus nerve stimulation through auricular branch along with task specific exercises

Group A will receive application of TENS to stimulate the vagus nerve at the ear level, apply the clip electrodes at the targus/cymba concha and the other electrode anywhere in the skin over neck Mode on TENS will be normal, with the width pulse of 250µs. FITT will be as follow Frequency of 25 Hz, Intensity 1mA, Time 30 minutes and the treatment will be of 5 days a week for 8 consecutive weeks

• For grip and release: Use a soft ball, putty, or other textured objects. The patient squeezes the object to strengthen their grip and then releases it.
• Reaching task: Place objects at varying distances in front of the patient. Encourage them to reach out with the affected arm to grasp the items and then bring them back.
• Bilateral arm movement: Encourage simultaneous reaching or moving with both arms (e.g., pushing against a wall or lifting a lightweight object) to promote symmetry and coordination. Improve coordination and function of both arms.
• Tabletop activities: Engaging in activities lik

Intervention Type: OTHER

Transcutaneous vagus nerve stimulation through cervical branch along with task specific exercises

Group B will receive application of TENS to stimulate the vagus nerve at the neck level, apply the pad electrodes at the anterior mid to neck and the other electrode over back of neck Mode on TENS will be normal, with the width pulse of 250µs. FITT will be as follow Frequency of 25 Hz, Intensity 1mA, Time 30 minutes and the treatment will be of 5 days a week for 8 consecutive weeks

• For grip and release: Use a soft ball, putty, or other textured objects. The patient squeezes the object to strengthen their grip and then releases it.
• Reaching task: Place objects at varying distances in front of the patient. Encourage them to reach out with the affected arm to grasp the items and then bring them back.
• Bilateral arm movement: Encourage simultaneous reaching or moving with both arms (e.g., pushing against a wall or lifting a lightweight object) to promote symmetry and coordination. Improve coordination and function of both arms.
• Tabletop activities: Engaging in activities like sortin

Intervention Type: OTHER

Eligibility Criteria

Inclusion Criteria

• First ever ischemic stroke
• Subacute phase of stroke 3-6 months post onset
• Fugl-Meyer Assessment-Upper Extremity (FMA-UE) scores ranged from 20 - 50

Exclusion Criteria

• Previous injury or surgical intervention of vagus nerve
• Patients with cardiac arrest and arrythmias
• Uncontrolled hypertension
• Apraxia
• Other neurologic or musculoskeletal diseases
• Presence of implanted electronic devices

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 70 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Lahore University of Biological and Applied Sciences

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Aruba Saeed

Role: PRINCIPAL_INVESTIGATOR

Lahore University of Biological and Applied Sciences

Locations

Shadman Medical Center, Stroke Rehabilitation

Lahore, Punjab Province, Pakistan

Site Status: RECRUITING

Countries

Pakistan

Central Contacts

Wafa Mansha, DPT

Role: CONTACT

wafamalik583@gmail.com

+92266303005

Aruba Saeed, PhD

Role: CONTACT

arubasaeedpt@gmail.com

+923344399403

References

Butt MF, Albusoda A, Farmer AD, Aziz Q. The anatomical basis for transcutaneous auricular vagus nerve stimulation. J Anat. 2020 Apr;236(4):588-611. doi: 10.1111/joa.13122. Epub 2019 Nov 19.

Reference Type: BACKGROUND

PMID: 31742681 (View on PubMed)

Murphy SJ, Werring DJ. Stroke: causes and clinical features. Medicine (Abingdon). 2020 Sep;48(9):561-566. doi: 10.1016/j.mpmed.2020.06.002. Epub 2020 Aug 6.

Reference Type: BACKGROUND

PMID: 32837228 (View on PubMed)

Hays SA, Rennaker RL, Kilgard MP. Targeting plasticity with vagus nerve stimulation to treat neurological disease. Prog Brain Res. 2013;207:275-99. doi: 10.1016/B978-0-444-63327-9.00010-2.

Reference Type: BACKGROUND

PMID: 24309259 (View on PubMed)

Hilz MJ. Transcutaneous vagus nerve stimulation - A brief introduction and overview. Auton Neurosci. 2022 Dec;243:103038. doi: 10.1016/j.autneu.2022.103038. Epub 2022 Sep 27.

Reference Type: BACKGROUND

PMID: 36201901 (View on PubMed)

Other Identifiers

UBAS/ERB/FoRS/25/O32 Wafa

Identifier Type: -

Identifier Source: org_study_id