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

NCT ID: NCT05943431

Last Updated: 2024-01-12

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 150 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2023-08-01
• Study Completion Date: 2025-12-01

Brief Summary

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.

Conditions

Upper Extremity Dysfunction; Stroke

Study Design

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

Study Groups

Paired taVNS

Upper extremity motor rehabilitation training will be paired with taVNS.

Group Type: EXPERIMENTAL

paired taVNS

Intervention Type: DEVICE

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.

Unpaired taVNS

Unpaired transcutaneous vagus nerve stimulation for upper limb motor rehabilitation will be administered.

Group Type: ACTIVE_COMPARATOR

Unpaired taVNS

Intervention Type: DEVICE

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 taVNS

Upper limb motor rehabilitation training will be paired with sham-stimulation.

Group Type: SHAM_COMPARATOR

Sham taVNS

Intervention Type: DEVICE

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.

Interventions

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.

Intervention Type: 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.

Intervention Type: 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.

Intervention Type: DEVICE

Eligibility Criteria

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.

• Minimum Eligible Age: 18 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Zhuhai Fudan Innovation Institute

UNKNOWN

Sponsor Role: collaborator

BrainClos Co., LTD.

UNKNOWN

Sponsor Role: collaborator

Qiuyou Xie

OTHER

Sponsor Role: lead

Responsible Party

Qiuyou Xie

principal investigator

Responsibility Role: SPONSOR_INVESTIGATOR

Principal Investigators

Qiuyou Xie, PhD

Role: PRINCIPAL_INVESTIGATOR

Southern Medical University, China

Locations

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, China

Site Status: RECRUITING

Countries

China

Central Contacts

Xue-Zhen XIAO, PhD

Role: CONTACT

xuezhenxiao@brainclos.com

+8613425122570

Rongdong Li, BSc

Role: CONTACT

13413627078@163.com

+86 15626216282

Facility Contacts

Qiuyou Xie, PhD

Role: primary

764942251@qq.com

+86 139 0301 9604

References

Dawson J, Liu CY, Francisco GE, Cramer SC, Wolf SL, Dixit A, Alexander J, Ali R, Brown BL, Feng W, DeMark L, Hochberg LR, Kautz SA, Majid A, O'Dell MW, Pierce D, Prudente CN, Redgrave J, Turner DL, Engineer ND, Kimberley TJ. Vagus nerve stimulation paired with rehabilitation for upper limb motor function after ischaemic stroke (VNS-REHAB): a randomised, blinded, pivotal, device trial. Lancet. 2021 Apr 24;397(10284):1545-1553. doi: 10.1016/S0140-6736(21)00475-X.

Reference Type: BACKGROUND

PMID: 33894832 (View on PubMed)

Liu Y, Zhang L, Zhang X, Ma J, Jia G. Effect of Combined Vagus Nerve Stimulation on Recovery of Upper Extremity Function in Patients with Stroke: A Systematic Review and Meta-Analysis. J Stroke Cerebrovasc Dis. 2022 Jun;31(6):106390. doi: 10.1016/j.jstrokecerebrovasdis.2022.106390. Epub 2022 Mar 22.

Reference Type: BACKGROUND

PMID: 35334250 (View on PubMed)

De Smet S, Ottaviani C, Verkuil B, Kappen M, Baeken C, Vanderhasselt MA. Effects of non-invasive vagus nerve stimulation on cognitive and autonomic correlates of perseverative cognition. Psychophysiology. 2023 Jun;60(6):e14250. doi: 10.1111/psyp.14250. Epub 2023 Jan 22.

Reference Type: BACKGROUND

PMID: 36683127 (View on PubMed)

Chang JL, Coggins AN, Saul M, Paget-Blanc A, Straka M, Wright J, Datta-Chaudhuri T, Zanos S, Volpe BT. Transcutaneous Auricular Vagus Nerve Stimulation (tAVNS) Delivered During Upper Limb Interactive Robotic Training Demonstrates Novel Antagonist Control for Reaching Movements Following Stroke. Front Neurosci. 2021 Nov 25;15:767302. doi: 10.3389/fnins.2021.767302. eCollection 2021.

Reference Type: BACKGROUND

PMID: 34899170 (View on PubMed)

Cook DN, Thompson S, Stomberg-Firestein S, Bikson M, George MS, Jenkins DD, Badran BW. Design and validation of a closed-loop, motor-activated auricular vagus nerve stimulation (MAAVNS) system for neurorehabilitation. Brain Stimul. 2020 May-Jun;13(3):800-803. doi: 10.1016/j.brs.2020.02.028. Epub 2020 Feb 27.

Reference Type: BACKGROUND

PMID: 32289710 (View on PubMed)

Monge-Pereira E, Molina-Rueda F, Rivas-Montero FM, Ibanez J, Serrano JI, Alguacil-Diego IM, Miangolarra-Page JC. Electroencephalography as a post-stroke assessment method: An updated review. Neurologia. 2017 Jan-Feb;32(1):40-49. doi: 10.1016/j.nrl.2014.07.002. Epub 2014 Oct 5. English, Spanish.

Reference Type: BACKGROUND

PMID: 25288536 (View on PubMed)

Badran BW, Peng X, Baker-Vogel B, Hutchison S, Finetto P, Rishe K, Fortune A, Kitchens E, O'Leary GH, Short A, Finetto C, Woodbury ML, Kautz S. Motor Activated Auricular Vagus Nerve Stimulation as a Potential Neuromodulation Approach for Post-Stroke Motor Rehabilitation: A Pilot Study. Neurorehabil Neural Repair. 2023 Jun;37(6):374-383. doi: 10.1177/15459683231173357. Epub 2023 May 20.

Reference Type: BACKGROUND

PMID: 37209010 (View on PubMed)

Provided Documents

Document Type: Study Protocol

View Document

Document Type: Informed Consent Form

View Document

Other Identifiers

L20230613

Identifier Type: -

Identifier Source: org_study_id