taVNS Paired With Motor Training for Upper-extremity Rehabilitation in Stroke Patients

January 10, 2024 updated by: Qiuyou Xie

A Randomized, Double-blind Controlled Trial Investigating the Efficacy of Transcutaneous Auricular Vagus Nerve Stimulation (taVNS) in Improving Upper Extremity Motor Function in Stroke Patients

Background: Recently, there has been increasing attention on the application of transcutaneous auricular vagus nerve stimulation (taVNS) in ischemic stroke. This innovative technique involves non-invasive electrical stimulation of the vagus nerve. A controlled study by Dawson et al. (2021), conducted using a randomized, double-blind approach, has demonstrated that vagus nerve stimulation (VNS) when paired with motor function training, can effectively promote the improvement of motor dysfunction in stroke patients. In the same year, the Food and Drug Administration approved the use of VNS, alongside motor rehabilitation training, for upper extremity dysfunction caused by stroke. However, it is worth noting that VNS requires surgical procedures with contraindications. Consequently, researchers are exploring taVNS as a potential alternative intervention. Compared to VNS, taVNS offers a low-risk and user-friendly intervention that eliminates the need for surgery and the associated postoperative complications. A recent meta-analysis has shown that the efficacy of taVNS in upper extremity rehabilitation for stroke patients can be comparable to that of VNS. Therefore, pairing taVNS with motor training holds promise as a valuable clinical tool for post-stroke rehabilitation.

Methods and Design: This study presents a protocol for a single-center randomized, double-blind controlled trial. A total of 150 participants will be enrolled and randomly assigned to one of three groups (Group 1, Group 2, or Group 3) in a 1:1:1 ratio. Each patient will undergo a total of 14 treatment sessions. In Group 1, patients will receive motor training paired with taVNS. In Group 2, patients will receive motor training and taVNS interventions, seperately. In Group 3, patients will receive motor training paired with sham taVNS. Primary and secondary outcome measures will be assessed at baseline and after taVNS treatment. The primary outcome will be determined by evaluating the behavioral response to treatment, using the Fugl-Meyer Assessment of Upper Extremity (FMA-UE).

Discussion: This study aims to elucidate the role of paired taVNS in the rehabilitation of upper extremity dysfunction in stroke patients. The researchers propose a novel approach by pairing taVNS with individualized training actions, utilizing electromyography (EMG) during motor training to precisely trigger taVNS.

Study Overview

Status

Recruiting

Conditions

Intervention / Treatment

Study Type

Interventional

Enrollment (Estimated)

150

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

  • China
    • Guangdong
      • Guangzhou, Guangdong, China, 510280
        • Recruiting
        • Zhujiang Hospital of Southern Medical University
        • 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:

  • Patients diagnosed with ischemic stroke according to a clinically qualified physician with reference to the Chinese Stroke Prevention and Control Guideline (2021).
  • Patients in the acute/recovery phase (after 2 weeks of onset) with stable signs;
  • No previous neuropsychiatric-related diseases;
  • No significant impairment of cognitive function and able to cooperate in completing the corresponding rehabilitation training;
  • With unilateral upper limb dysfunction;
  • Patients who have not received various neuromodulation rehabilitation treatments;
  • No contraindications to taVNS;
  • Patients voluntarily cooperated with the study and signed an informed consent form.

Exclusion Criteria:

  • Patients have other mental health disorders (dementia, Parkinson's disease, depression, schizophrenia, bipolar disorder, etc.)
  • Patients have uncontrolled epilepsy, i.e., having had a seizure within 4 weeks prior to enrollment
  • Patients have cardiac arrhythmias or other abnormalities
  • Patients have a history of respiratory disease or disorder, including dyspnea and asthma;
  • The presence of gastrointestinal disorders such as diarrhea and vomiting that make it difficult for the patient to cooperate
  • Patients have a history of vasovagal syncope
  • Patients are under treatment with other neurostimulation/modulation
  • The presence of severe spasticity, other serious injuries to the upper extremities, or other medical conditions
  • Patients have difficulty in communication and understanding and inability to cooperate in completing the test;
  • Women who are pregnant or breastfeeding.

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: Quadruple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Paired taVNS
Upper extremity motor rehabilitation training will be paired with taVNS.
Device: paired taVNS
The stimulator will be placed on the left ear of the patient. While the patient performs the action training, the EMG signal feature evoked by the action will trigger an electrical stimulation of the transcutaneous auricular vagus nerve. The amplitude of the electrical stimulation will be adjusted under the patient's pain threshold. The intervention will be performed daily for 14 days.
Active Comparator: Unpaired taVNS
Unpaired transcutaneous vagus nerve stimulation for upper limb motor rehabilitation will be administered.
Device: Unpaired taVNS
The stimulator will be placed on the patient's left ear. Patients will receive taVNS with pulses every 5-7 seconds. Following the stimulation, motor training will be performed. The motor training will be identical to that of the paired group. The amplitude of the electrical stimulation will be adjusted under the patient's pain threshold. The intervention will be performed daily for 14 days.
Sham Comparator: Sham taVNS
Upper limb motor rehabilitation training will be paired with sham-stimulation.
Device: Sham taVNS
The stimulator will be placed on the patient's left ear. The amplitude of the electrical stimulation will be adjusted at 0 mA. The intervention will be performed daily for 14 days.

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes from Baseline Fugl-Meyer Assessment of Upper Extremity (FMA-UE) Scores
Time Frame: Immediately after 14 days' sessions

The Fugl-Meyer Assessment - Upper Extremity (FMA-UE) is a stroke-specific assessment that measures performance at the body function/impairment domain. It uses an ordinal scale for scoring 33 items for the upper limb function with a total possible score of 66. The FMA-UE is one of the most widely used quantitative measures of motor impairment after stroke. Studies have shown excellent inter-rater, and intra-rater reliability, and construct validity of FMA-UE. In addition, empirical evidence suggests that the FMA-UE is responsive to the change in rehabilitation. Higher scores are indicative of better outcomes.

The primary outcome measures are as follows:

  1. Difference in the changes from baseline FMA-UE scores between paired taVNS and shame taVNS groups.
  2. Difference in the changes from baseline FMA-UE scores between unpaired taVNS and shame taVNS groups.
  3. Difference in the changes from baseline FMA-UE scores between paired taVNS and unpaired taVNS groups.
Immediately after 14 days' sessions

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Changes from Baseline Wolf motor function test (WMFT)
Time Frame: Immediately after 14 days' sessions

The Wolf motor function test (WMFT) is a widely used measure for upper extremity motor abilities. It uses a 6-point ordinal scale for scoring 17 items with a total core of 85. Higher scores are indicative of better outcomes.

We will compare the differences in the changes from baseline WMFT scores between paired taVNS and shame taVNS groups, between unpaired taVNS and shame taVNS groups, and between paired taVNS and unpaired taVNS groups.
Immediately after 14 days' sessions
Changes from Baseline Brunnstrom recovery stages (BRS)
Time Frame: Immediately after 14 days' sessions

The Brunnstrom recovery stages (BRS) is a measure for assessing motor function. The BRS contains 3 items rated on a 6-level Likert-type scale. Higher scores are indicative of better outcomes.

We will compare the differences in the changes from baseline BRS scores between paired taVNS and shame taVNS groups, between unpaired taVNS and shame taVNS groups, and between paired taVNS and unpaired taVNS groups.
Immediately after 14 days' sessions
Changes from Baseline Barthel Index (BI)
Time Frame: Immediately after 14 days' sessions

The Barthel Index (BI) is a measure of independence in the activities of daily living (ADLs). The BI includes the 10 ADLs with a total score of 100. Higher scores are indicative of better outcomes.

We will compare the differences in the changes from baseline BI scores between paired taVNS and shame taVNS groups, between unpaired taVNS and shame taVNS groups, and between paired taVNS and unpaired taVNS groups.
Immediately after 14 days' sessions
Changes from Baseline Hong Kong version of the Functional Test for the Hemiplegic Upper Extremity (FTHUE-HK)
Time Frame: Immediately after 14 days' sessions

The Hong Kong version of the Functional Test for the Hemiplegic Upper Extremity (FTHUE-HK) is another measure for ADL. It uses a 7-point ordinal scale for scoring 12 items with a total score of 84. Higher scores are indicative of better outcomes.

We will compare the differences in the changes from baseline FTHUE-HK scores between paired taVNS and shame taVNS groups, between unpaired taVNS and shame taVNS groups, and between paired taVNS and unpaired taVNS groups.
Immediately after 14 days' sessions
Changes from Baseline EMG features
Time Frame: Immediately after 14 days' sessions

EMG will be acquired from 2 channels on the upper limb. When participants perform motor training, the peak amplitudes and the zero crossing rate of EMG signals at the time domain and the relative spectral power (RSP) of EMG signals at 20 to 200 Hz will be calculated on-line.

  1. Difference in the changes from baseline EMG features between paired taVNS and shame taVNS groups.
  2. Difference in the changes from baseline EMG features scores between unpaired taVNS and shame taVNS groups.
  3. Difference in the changes from baseline EMG features scores between paired taVNS and unpaired taVNS groups.
Immediately after 14 days' sessions
Changes from Baseline EEG features
Time Frame: Immediately after 14 days' sessions

EEG will be acquired from 66 channels following the international 10-20 System for 10 mins. The relative spectral power (RSP) of participants will be calculated by the selected artifact-free EEG epochs at five frequency bands: δ (1-4 Hz), θ (4-8 Hz), α (8-13 Hz), β (13-30 Hz), and γ (30-45 Hz). The investigators will perform off-line analysis to calculate RSP.

  1. Difference in the changes from baseline EEG features between paired taVNS and shame taVNS groups.
  2. Difference in the changes from baseline EEG features scores between unpaired taVNS and shame taVNS groups.
  3. Difference in the changes from baseline EEG features scores between paired taVNS and unpaired taVNS groups.
Immediately after 14 days' sessions

Collaborators and Investigators

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

Sponsor

Qiuyou Xie

Collaborators

BrainClos Co., LTD.
Zhuhai Fudan Innovation Institute

Investigators

  • Principal Investigator: Qiuyou Xie, PhD, Southern Medical University, China

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

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)

August 1, 2023

Primary Completion (Estimated)

July 1, 2025

Study Completion (Estimated)

December 1, 2025

Study Registration Dates

First Submitted

June 25, 2023

First Submitted That Met QC Criteria

July 4, 2023

First Posted (Actual)

July 13, 2023

Study Record Updates

Last Update Posted (Actual)

January 12, 2024

Last Update Submitted That Met QC Criteria

January 10, 2024

Last Verified

January 1, 2024

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • L20230613

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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