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

May 10, 2024 updated by: Engy Badreldin Saleh Moustafa, PhD, Cairo University

Neural-Plasticity Biomarkers, Interleukin-6 and Motor Performance in Response to Non-Invasive Vagus Nerve Stimulation After Stroke: A Randomized Controlled Clinical Trial

Forty-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.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Detailed Description

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: Forty-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.

Study Type

Interventional

Enrollment (Estimated)

50

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Contact

Study Contact Backup

Study Locations

  • Egypt
    • Ad Doqi, Giza District, Giza Governorate
      • Giza, Ad Doqi, Giza District, Giza Governorate, Egypt, 11432
        • Recruiting
        • Faculty of Physical Therapy, Cairo University
        • Contact:
        • Contact:

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

  • Adult
  • Older Adult

Accepts Healthy Volunteers

No

Description

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 .

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

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

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Placebo Comparator: 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.
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.
Experimental: 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.
Device: 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.

Other Names:
  • Transcutaneous Vagus Nerve Stimulation (TVNS)

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Muscle tone of the upper limb
Time Frame: Baseline Assessment and Immediately Post Treatment.
The Modified Ashworth Scale (MAS) will be used; it is a six-point ordinal scale. It ranges from 0 (no increase in muscle tone) to 4 (affected part rigid in flexion or extension). The muscle tone was measured by observing the response of the muscle group to the resistance of passive movement in the affected hand. The degree of muscle tone in the affected hand was classified as (0 = normal, 1 or 1+ = mild, 2 or 3 = moderate, or 4 = severe).
Baseline Assessment and Immediately Post Treatment.
Gross hand dexterity
Time Frame: Baseline Assessment and Immediately Post Treatment.
The Box and Blocks Test (BBT) will be used; it is a quick, simple, and inexpensive test for measuring unilateral gross manual dexterity in stroke. The patients were asked to transfer as many blocks as they could from one compartment to the other for 60 seconds. The patient was allowed to choose any block of any color and to carry only one block each time with his hand, which must cross over the partition.
Baseline Assessment and Immediately Post Treatment.
Level of Plasma brain-derived Derived factor (BDNF)
Time Frame: Baseline Assessment and Immediately Post Treatment.
Sandwich-ELISA kits will be used according to the manufacturer's instructions. Venous blood samples were collected in a disposable plastic vacuum tube with an anticoagulant. Samples were centrifuged for 15 min at 1000×g at 2-8 °C within 30 min of collection.
Baseline Assessment and Immediately Post Treatment.
Level of Serum Interleukin IL-6
Time Frame: Baseline Assessment, Immediately Post Treatment, 3 Month Posttreatment Assessment (Follow-up)
Interleukin-6 (IL-6) is a crucial inflammatory factor in that its significant increase was observed in stroke patients shortly following the ischemic event and serves a vital role as a messenger molecule between leucocytes, the vascular endothelium, and parenchyma. A single referral lab will test the samples using ELISA and U/CyTech kits. From each participant, 10 milliliters of non-fasting blood sample will be obtained 6 to 24 hours after the onset of symptoms and kept in citrate tubes. Blood samples will thereafter centrifuged within 1 hour at 3000 × g for 15 minutes at 4°C and resultant plasma will be kept in -80°C.
Baseline Assessment, Immediately Post Treatment, 3 Month Posttreatment Assessment (Follow-up)

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Cairo University

Investigators

  • Principal Investigator: Engy B Saleh, PhD, Faculty of Physical Therapy, Cairo University, Egypt

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 21, 2024

Primary Completion (Estimated)

May 23, 2024

Study Completion (Estimated)

June 9, 2024

Study Registration Dates

First Submitted

April 19, 2024

First Submitted That Met QC Criteria

April 24, 2024

First Posted (Actual)

April 29, 2024

Study Record Updates

Last Update Posted (Actual)

May 13, 2024

Last Update Submitted That Met QC Criteria

May 10, 2024

Last Verified

May 1, 2024

More Information

Terms related to this study

Additional Relevant MeSH Terms

Other Study ID Numbers

  • P.T.REC/012/005107

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

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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