Plasticity Biomarkers,Interleukin-6 and Motor Performance in Response to Vagus Nerve Stimulation After Stroke

NCT ID: NCT06388954

Last Updated: 2025-05-13

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

RECRUITING

Clinical Phase

NA

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2024-05-28

Study Completion Date

2025-05-18

Brief Summary

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Seventy-eight clinically verified Egyptian patients from both sexes with ischemic stroke that occurred at least 6 months to 2 years before inclusion will be randomly assigned into 2 groups, control group (GA) and the experimental group (GB). Patients will be randomly assigned into two equal groups: the control group (GA) and the experimental group (GB). Patients in the control group (GA) will be treated with sham Vagus nerve stimulation (taVNS) immediately before a selected physical therapy program, while in the experimental group (GB), patients will receive real transcutaneous auricular Vagus nerve stimulation (taVNS) followed by the same selected physical therapy program as (GA). Plasma level of Brain-Derived Neurotrophic Factors (BDNF) and Interleukin-6 (IL-6), Box and Blocks Test (BBT), and modified Ashworth scale (MAS) will be assessed at baseline and immediately post-treatment.

Detailed Description

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Background: Neuromodulation techniques play an integral role in restoring motor function in stroke patients by affecting the adaptive neuroplasticity and activation of neuromodulators that may reduce brain inflammation post stroke.

Objective: To assess the efficacy of transcutaneous auricular vagal nerve stimulation on plasma levels of Brain-Derived Neurotrophic Factors (BDNF), Interleukin-6 (IL-6), gross manual dexterity, and muscle tone in patients with ischemic stroke.

Materials and Methods: Seventy-eight clinically verified Egyptian patients from both sexes with ischemic stroke that occurred at least 6 months to 2 years before inclusion, aged 55 to 65 years, were recruited. Patients will be randomly assigned into two equal groups; control group (GA) and the experimental group (GB). Patients in the control group (GA) were treated with sham Vagus nerve stimulation (taVNS) immediately before a selected physical therapy program, while in the experimental group (GB), patients received real transcutaneous auricular Vagus nerve stimulation (taVNS) followed by the same selected physical therapy program as (GA). Plasma levels of Brain-Derived Neurotrophic Factors (BDNF), serum Interleukin-6 (IL-6) , Box and Blocks Test (BBT) and Modified Ashworth scale (MAS) were assessed at baseline and immediately post-treatment.

Results: There was a statistically significant improvement in BBT, plasma IL-18 level and BDNF in experimental group (GB) post-treatment (P\< 0.05) with no change in MAS. There was no statistical significant difference in BBT, plasma Interleukin-6 (IL-6) and MAS in control group post treatment (P\> 0.05). While, there is a statistically significant improvement in BDNF in the control group post treatment. A statistically significant improvement was observed of BBT and BDNF in the study group compared to the control group (P\< 0.05). There was no statistical significant difference in MAS between study and control groups (P\> 0.05).

Conclusions: Non-invasive VNS as an adjunct to conventional physical rehabilitation enhances neuroplasticity and improves upper limb motor ability after ischemic stroke, as well as reducing the stroke-induced inflammatory process, which may affect the disease prognosis.

Conditions

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Stroke Motor Disorders

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Single-blind, randomized controlled study.
Primary Study Purpose

TREATMENT

Blinding Strategy

SINGLE

Participants
Patients participated will be masked about the type of intervention, where (GA) patients will receive physical therapy program + sham transcutaneous auricular Vagus nerve stimulation, while patients in (GB) will receive true transcutaneous auricular Vagus nerve stimulation in addition to the same physical therapy program as (GA).

Study Groups

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Control group (GA)

Patients in the control group (GA) will be treated by 12 sessions of sham transcutaneous auricular Vagus nerve stimulation for 30 minutes immediately, will be followed by 30 minutes of a selected physical therapy program, three sessions per week for four consecutive weeks. Sham transcutaneous vagal nerve stimulation was performed using the same procedures as the study group but without electrical stimulation.

Group Type PLACEBO_COMPARATOR

Sham Trancutaneous auricular Vagus Nerve Stimulation

Intervention Type DEVICE

Sham transcutaneous vagal nerve stimulation will be performed by the same procedures of the study group but without electrical stimulation. The active electrodes will be attached to the left cymba conchae. The taVNS stimulator will be turned on and the stimulation intensity will be increased until the patient perceived the electrical stimulation and then the stimulator will be turned off.

Study group (GB)

Patients in the study group (GB) will be treated by 12 sessions of true transcutaneous auricular Vagus nerve stimulation for 30 minutes , then immediately followed by 30 minutes of a selected physical therapy program (GA), three sessions per week for four consecutive weeks. The stimulation of the auricular branch of the Vagus nerve will be performed by conventional TENS device with one channel and two electrodes.

Group Type EXPERIMENTAL

True Transcutaneous auricular Vagus Nerve Stimulation (TaVNS)

Intervention Type DEVICE

Vagus Nerve Stimulation (VNS) consists in the activation of the Vagus nerve using electrical current, Transcutaneous auricular VNS works through the placement of noninvasive electrodes on the neck or auricle for stimulation of the auricular branch of the vagus nerve.

Transcutaneous electrical nerve stimulation (TENS) electrodes will be used to stimulate the auricular branch of the Vagus nerve, The active electrode will be placed on the cymba concha of the left ear. This reduced the risk of taVNS side effect on the heart. The reference electrode will be placed outside the left ear attached to the tragus. TENS parameters used were: 30 minutes treatment time, a pulse width of 300 microseconds, pulse frequency 20 hertz and a duty cycle of 25%. The stimulation intensity was set at super-threshold levels, such as 200% of patient perceptual threshold.

Interventions

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True Transcutaneous auricular Vagus Nerve Stimulation (TaVNS)

Vagus Nerve Stimulation (VNS) consists in the activation of the Vagus nerve using electrical current, Transcutaneous auricular VNS works through the placement of noninvasive electrodes on the neck or auricle for stimulation of the auricular branch of the vagus nerve.

Transcutaneous electrical nerve stimulation (TENS) electrodes will be used to stimulate the auricular branch of the Vagus nerve, The active electrode will be placed on the cymba concha of the left ear. This reduced the risk of taVNS side effect on the heart. The reference electrode will be placed outside the left ear attached to the tragus. TENS parameters used were: 30 minutes treatment time, a pulse width of 300 microseconds, pulse frequency 20 hertz and a duty cycle of 25%. The stimulation intensity was set at super-threshold levels, such as 200% of patient perceptual threshold.

Intervention Type DEVICE

Sham Trancutaneous auricular Vagus Nerve Stimulation

Sham transcutaneous vagal nerve stimulation will be performed by the same procedures of the study group but without electrical stimulation. The active electrodes will be attached to the left cymba conchae. The taVNS stimulator will be turned on and the stimulation intensity will be increased until the patient perceived the electrical stimulation and then the stimulator will be turned off.

Intervention Type DEVICE

Other Intervention Names

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Transcutaneous Vagus Nerve Stimulation (TVNS)

Eligibility Criteria

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Inclusion Criteria

* Hemiparetic patients with ischemic middle cerebral artery stroke
* The duration of illness ranged from at least 6 months to 2 years after stroke.
* Patient's age ranged from 55 to 65 years, patients with unilateral upper limb motor function impairment.
* Patients able to transfer at least one block in Box and Blocks Test.
* Patients with sufficient cognitive abilities that enables them to understand and follow instructions.
* Spasticity of upper limb muscles ranged from (grade 1:2) according to Modified Ashworth scale.

Exclusion Criteria

* Other neurological diseases that affect upper limb function other than stroke (e.g.: Multiple sclerosis, peripheral neuropathy, Parkinsonism….etc.).
* Hemorrhagic stroke
* Visual or auditory impairment affecting their ability to complete the testing.
* Cognitive impairment.
* Cardiovascular problems and pulmonary or kidney disorders
* Musculoskeletal disorders (e.g. scoliosis, kyphosis, severe arthritis…etc.)
* Severe spasticity (a Modified Ashworth Scale score ≥3).
* Patients with any taVNS contraindications such as previous surgical intervention on Vagus nerve.
* Low blood pressure (\<100/60mmHg) or low heart rate (\<60bpm) and or high blood pressure (\>220/130 mmHg).
* Pacemaker or other implanted electrical device.
* Any current or past history of cardiovascular disorders
* Facial or ear pain
* Recent ear trauma .
Minimum Eligible Age

55 Years

Maximum Eligible Age

65 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Cairo University

OTHER

Sponsor Role lead

Responsible Party

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Engy Badreldin Saleh Moustafa, PhD

Principal Investigator

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Engy B Saleh, PhD

Role: PRINCIPAL_INVESTIGATOR

Faculty of Physical Therapy, Cairo University, Egypt

Locations

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Faculty of Physical Therapy, Cairo University

Giza, Dokki, Egypt

Site Status RECRUITING

Countries

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Egypt

Central Contacts

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Engy B Saleh, PhD

Role: CONTACT

00201099445112

Moshera H. Darwish, PhD

Role: CONTACT

00201015163617

Facility Contacts

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Engy BadrEldin S Moustafa, PhD

Role: primary

00201099445112

Moshera H. Darwish, PhD

Role: backup

00201015163617

Other Identifiers

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P.T.REC/012/005107

Identifier Type: -

Identifier Source: org_study_id

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