Wether VNS in Early Stage (3 Months) is Safe and More Beneficial for Post-stroke Motor Rehabilitation

The Comparison of Safety and Treatment Results Between Early (<6 Months) and Late (> 6 Months) Vagus Stimulation for Post-stroke Motor Rehabilitation: a Randomized Clinical Trial

Upper-extremity impairment after stroke remains a major therapeutic challenge and a target of neuromodulation treatment efforts. In previous study, Vagus nerve stimulation was constricted to patients 9 months after stroke. In this randomized phase I trial, we would apply vagus nerve stimulation in an early stage (<6 month) and observe its theraputic effect on motor function after ischaemic Stroke.We hypothesized that the early stimulation could be safe and more beneficial compared to stimulation in late stage.

Study Overview

• Status: Recruiting
• Conditions: Stroke; Motor Rehabilitation
• Intervention / Treatment: Device: Vagus Nerve Stimulation in late stage; Device: Vagus Nerve Stimulation in early stage

• Study Type: Interventional
• Enrollment (Estimated): 100
• Phase: Phase 1

Contacts and Locations

• Study Contact: Name: Chao Zhang; Phone Number: 13969007232; Email: chao_zhang@sdu.edu.cn

Study Locations

• China
  • Sichuan
    • Jinan, Sichuan, China, 250100
      • Recruiting
      • Qilu Hospital of Shandong University
      • Contact: Chao Zhang; Phone Number: 13969007232; Email: chao_zhang@sdu.edu.cn

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Eligible individuals suffered a first-time, unilateral, ischemic stroke in the middle cerebral artery territory that spared the diencephalon and basal ganglia 3-36 months before surgery.

  • Individuals with persistent moderate-to-severe upper-extremity hemiparesis as defined by an FM-UE score of ≤42
  • Sufficient upper-extremity motor ability to engage in rehabilitation (that is, a score of ≥1 on the FM-UE elbow flexion, elbow extension or finger mass flexion or extension).

Exclusion Criteria:

• Excessive spasticity or contracture of the upper-extremity muscles (that is, Modified Ashworth Scale = 4) . Severe cognitive impairment (Mini Mental State Examination < 24)

Study Plan

How is the study designed?

Design Details

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

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VNS activated in late stage; Following enrollment, participants with a history of stroke greater than 6 months underwent 1 month of upper-extremity rehabilitation twice per week to rule out potential for recovery with rehabilitation therapy alone. Thereafter, each participant underwent surgical implantation of the VNS system. 1 months later, VNS was activated.	Device: Vagus Nerve Stimulation in late stage; Device implantation was done under general anaesthesia. A horizontal neck crease incision was created left of the midline at the level of the cricoid cartilage. After the vagus nerve was identified, the stimulation lead was wrapped around the vagus nerve. The lead was then tunnelled subcutaneously to the pulse generator device which was contained in a subcutaneous pocket in the pectoral region
Active Comparator: VNS activated in early stage; Following enrollment, participants with a history of stroke within 6 months underwent 1 month of upper-extremity rehabilitation twice per week to rule out potential for recovery with rehabilitation therapy alone. Thereafter, each participant underwent surgical implantation of the VNS system. 1 months later, VNS was activated.	Device: Vagus Nerve Stimulation in early stage; Device implantation was done under general anaesthesia. A horizontal neck crease incision was created left of the midline at the level of the cricoid cartilage. After the vagus nerve was identified, the stimulation lead was wrapped around the vagus nerve. The lead was then tunnelled subcutaneously to the pulse generator device which was contained in a subcutaneous pocket in the pectoral region.
Experimental: VNS not activated in early stage; Following enrollment, participants with a history of stroke within 6 months underwent 1 month of upper-extremity rehabilitation twice per week to rule out potential for recovery with rehabilitation therapy alone. Thereafter, each participant underwent surgical implantation of the VNS system.When the a history of stroke was exceeded over 6 months, VNS was activated.	Device: Vagus Nerve Stimulation in late stage; Device implantation was done under general anaesthesia. A horizontal neck crease incision was created left of the midline at the level of the cricoid cartilage. After the vagus nerve was identified, the stimulation lead was wrapped around the vagus nerve. The lead was then tunnelled subcutaneously to the pulse generator device which was contained in a subcutaneous pocket in the pectoral region

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
FM-UE scores between early and late VNS	The outcomes includes each participant's Fugl-Meyer assessment scale (FM-UE) scores for each monthly visit. FM-UE scores range from 0 to 100 and the higher scores indicated better outcome of movement.	12 months after device implantation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Arm Motor Ability Test (AMAT) between early and late VNS	The outcomes includes each participant's the Arm Motor Ability Test (AMAT) for each monthly visit. AMAT scores range from 0 to 57 and the higher scores indicated better outcome of movement.	12 months after device implantation
the Nine-Hole Peg Test between early and late VNS	The outcomes includes each participant's the Nine-Hole Peg Test for each monthly visit.	12 months after device implantation
the Bilateral Box and Block Test between early and late VNS	The outcomes includes each participant's the Bilateral Box and Block Test for each monthly visit.	12 months after device implantation
Short Form Health Survey (SF-12) between early and late VNS	The outcomes includes each participant's score of Short Form Health Survey (SF-12) for each monthly visit. SF-12 scores range from 0 to 60 and the higher scores indicated better outcome of movement.	12 months after device implantation
the EuroQol Five Dimensions Questionnaire (EQ-5D) between early and late VNS	The outcomes includes each participant's score of the EuroQol (EQ-5D) scores range from 0 to 36 for each monthly visit.	12 months after device implantation
safety and feasibility of early and late VNS	The incidence of adverse events including hemorrhages, infections, deaths or major perioperative complications during the study	12 months after device implantation

Collaborators and Investigators

• Sponsor: Qilu Hospital of Shandong University

Study record dates

Study Major Dates

• Study Start (Estimated): May 1, 2025
• Primary Completion (Estimated): May 1, 2026
• Study Completion (Estimated): December 30, 2026

Study Registration Dates

• First Submitted: April 14, 2025
• First Submitted That Met QC Criteria: April 14, 2025
• First Posted (Actual): April 22, 2025

Study Record Updates

• Last Update Posted (Actual): April 22, 2025
• Last Update Submitted That Met QC Criteria: April 14, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: Hemiparesis; VNS; Limb Motor Function Rehabilitation
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Stroke
• Other Study ID Numbers: Early VNS for Motor Rehabilita

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No