Effect of Non-invasive Vagus Nerve Stimulation on Cerebrovascular Reactivity and Cognition in Chronic Stroke Patients

This study will be conducted to assess the effect of non-invasive vagus nerve stimulation on cerebrovascular reactivity and cognition in chronic stroke patients

Study Overview

• Status: Not yet recruiting
• Conditions: Stroke
• Intervention / Treatment: Device: Trans-auricular vagus nerve stimulation; Other: Conventional physical therapy; Device: Computer based cognitive rehabilitation training; Device: Sham trans-auricular vagus nerve stimulation

Detailed Description

Stroke is a leading cause of disability worldwide, resulting in physical, cognitive, and emotional impairments. These impairments significantly affect individuals, families, and communities. It imposes a substantial social and financial burden on healthcare systems and economies. Deficits in cognitive functions are highly associated with reduced treatment outcomes after stroke. This interferes with social and occupational recovery and limit psychosocial functioning.

Introducing new therapeutic methods such as non-invasive vagus nerve stimulation (VNS) alongside traditional rehabilitation is essential for enhancing cognitive function after stroke. Vagus nerve stimulation can be invasive or non-invasive. Non-invasive method of VNS via transcutaneous stimulation of the peripheral auricular branch of the Vagus nerve (taVNS) is safer, better-tolerated method for delivering VNS with the same effect of invasive VNS.

There are few key human studies that assessed the effects of transcutaneous vagus nerve stimulation (tVNS) on cerebrovascular reactivity (CVR) and cognition in chronic stroke patients. Up to our knowledge, this is the first Egyptian study that will assess the effect of transcutaneous vagus nerve stimulation on cerebrovascular reactivity and cognition in chronic stroke patients. This study will hopefully be of benefit in the physical therapy field. This may guide rehabilitation programs of physical therapy toward better results.

• Study Type: Interventional
• Enrollment (Estimated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Ahmed Kamal; Phone Number: 01110053571; Email: kamsafahm567@gmaol.com
• Study Contact Backup: Name: Marwa Abd El-Moneim, PHD; Phone Number: 01005661591; Email: marwa.mostafa@cu.edu.eg

Study Locations

• Egypt
  • Cairo, Egypt
    • Ahmed Safwat Kamal

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Forty chronic ischemic hemiparetic patients, of both sexes, will represent the sample.
• The patient's age will range from 50 to 60 years old.
• Duration of illness will range from six months to twelve months.
• Patients with mild cognitive impairment according to Montreal Cognitive Assessment (MoCA) scale (from 18 to 25).
• Spasticity will be 1 or 1+ according to Modified Aschworth scale.
• Educated patients.

Exclusion Criteria:

• The patients will be excluded if they have one of the followings:
• Patients with other neurological disease that affect cognition.
• Visual, verbal or hearing impairments that can interfere with communication.
• Depression assessed by Hamilton Depression Scale (Ham-D).
• Patients with poor bone window.
• History of psychiatric disease.
• Hemorrhagic stroke patients.
• Uncontrolled blood pressure or low heart rate.
• Uncontrolled diabetes (>130 mg/dL especially if consistently over 150 to 160 mg/dL)
• Patients with any taVNS contraindications (open heart surgery, pacemaker or other implants, previous surgical intervention on Vagus nerve, Facial or ear pain, and recent ear trauma)
• Stroke patients with severe cognitive impairment.
• Uncooperative patients.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: True trans-auricular vagus nerve stimulation group; Patients will receive true trans-auricular vagus nerve stimulation and computer based cognitive rehabilitation training (CBCR; RehaCom), in addition to conventional physical therapy program.	Device: Trans-auricular vagus nerve stimulation; Transcutaneous vagal nerve stimulation will be done through EME Therapic 9200 electrotherapy device (EME Physio, Via degli Abeti 88/161122 Pesaro (PU), Italy). A clip electrode will be applied on cymba conchae of left ear. Stimulation parameters will be set to 30 minutes treatment time, a pulse width of 300 microseconds, pulse frequency 30 HZ and a pulsed mode with a duty cycle of 50% (30 sec on and 30 sec off time).; Other: Conventional physical therapy; The physical therapy program will include strengthening exercises to the antispastic muscles, stretching exercises to spastic muscles, gait training exercises, proprioceptive neuromuscular facilitation exercises for upper limb and lower limb, and graduated balance exercise.; Device: Computer based cognitive rehabilitation training; RehaCom (Dr. G. Schuhfrted Ges.m.b.II., model No. A-2340 device) will be used in this study for assessment and training two cognitive domains: attention/concentration and figural memory. Each patient will be in a comfortable sitting position in front of a screen during the session. The two domains will be assessed at the end of each session.; Attention/concentration domain (AC) includes 24 levels of difficulty. Assessment will start at level one and will be advanced to more challenging levels.; Figural memory domain includes nine levels of difficulty. Assessment will start at level one and will be advanced to more challenging levels. Each cognitive training session will last 30 minutes, with 15 minutes dedicated to each targeted domain.
Active Comparator: Sham trans-auricular vagus nerve stimulation group; Patients will receive sham trans-auricular vagus nerve stimulation (ta-VNS), and computer based cognitive rehabilitation training (CBCR; RehaCom) in addition to conventional physical therapy program.	Other: Conventional physical therapy; The physical therapy program will include strengthening exercises to the antispastic muscles, stretching exercises to spastic muscles, gait training exercises, proprioceptive neuromuscular facilitation exercises for upper limb and lower limb, and graduated balance exercise.; Device: Computer based cognitive rehabilitation training; RehaCom (Dr. G. Schuhfrted Ges.m.b.II., model No. A-2340 device) will be used in this study for assessment and training two cognitive domains: attention/concentration and figural memory. Each patient will be in a comfortable sitting position in front of a screen during the session. The two domains will be assessed at the end of each session.; Attention/concentration domain (AC) includes 24 levels of difficulty. Assessment will start at level one and will be advanced to more challenging levels.; Figural memory domain includes nine levels of difficulty. Assessment will start at level one and will be advanced to more challenging levels. Each cognitive training session will last 30 minutes, with 15 minutes dedicated to each targeted domain.; Device: Sham trans-auricular vagus nerve stimulation; Patients will receive false trans-auricular vagus nerve stimulation through EME Therapic 9200 electrotherapy device (EME Physio, Via degli Abeti 88/161122 Pesaro (PU), Italy). The ear clip electrode will be attached to the center of the left earlobe of the patient, as it is free from vagus innervation. Stimulation parameters will be set to 30 minutes treatment time, a pulse width of 300 microseconds, pulse frequency 30 HZ and a pulsed mode with a duty cycle of 50% (30 sec on and 30 sec off time).

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Breathing holding index	Transcranial doppler ultrasonography technique will be used to assess cerebrovascular reactivity by measuring the percentage increase in cerebral blood flow velocity during apnea, divided by the duration of breath hold in seconds. Breath holding index will be calculated according to the following equation: BHI= ((Mean Flow Velocity (MFV) post- Mean Flow Velocity (MFV)rest/ Mean Flow Velocity (MFV)rest) × (100/Duration in second)) normal range:1.03-1.65.	4 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Montreal Cognitive Assessment Scale (MOCA):	It will be used to assess cognition before and after treatment period for all patients. Each patient will be asked to write and draw using the non-affected hand. The test consists of a single page, with reading items presented in a clear and appropriately sized font. The assessment will include short-term memory, executive functions, visuospatial abilities, language, attention, concentration, working memory, and temporal and spatial orientation. Total score of MoCA is from 0 to 30. From 26-30 is normal cognition, from 18-25 is mild cognitive impairment (MCI), from 10-17 is moderate cognitive impairment, and less than ten is Severe cognitive impairment.	4 weeks
Attention/concentration domain (AC)	RehaCom (Dr. G. Schuhfrted Ges.m.b.II., model No. A-2340 device) will be used in this study to assess and rehabilitate the cognitive function in stroke patients. It is a valid and reliable instrument for assessing and improving cognitive functions in stroke patients. Attention/concentration domain (AC) includes 24 levels of difficulty. Assessment will start at level one and will be advanced to more challenging levels. normal range :10-12 level; indicative cognitive impairment: below 10 level	4 weeks
Figural memory domain	RehaCom (Dr. G. Schuhfrted Ges.m.b.II., model No. A-2340 device) will be used in this study to assess and rehabilitate the cognitive function in stroke patients. It is a valid and reliable instrument for assessing and improving cognitive functions in stroke patients. Figural memory domain includes 9 levels of difficulty. Assessment will start at level one and will be advanced to more challenging levels. normal range :7-8 level; indicative cognitive impairment: below 7 level	4 weeks

Collaborators and Investigators

• Sponsor: Cairo University
• Investigators: Study Director: Mohamed Soliman, Professor, Cairo university; Study Director: Shimaa Mohamed, Professor, Cairo university; Study Chair: Moshera Darwish, Professor, Cairo university

Study record dates

Study Major Dates

• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): February 15, 2027
• Study Completion (Estimated): February 28, 2027

Study Registration Dates

• First Submitted: May 31, 2026
• First Submitted That Met QC Criteria: May 31, 2026
• First Posted (Actual): June 4, 2026

Study Record Updates

• Last Update Posted (Actual): June 4, 2026
• Last Update Submitted That Met QC Criteria: May 31, 2026
• Last Verified: May 1, 2026

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: P.T.REC/012/006121

Drug and device information, study documents

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