Cerebellar Deep Brain Stimulation or VNS for Chronic Post-stroke Motor Rehabilitation

The Comparison of Treatment Results Between Cerebellar DBS and 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 this open-label, randomized phase I trial, we applied deep brain stimulation to the cerebellar dentate nucleus combined with bilateral or unilateral stimulation. Vagus nerve stimulation was also conducted for motor function after ischaemic Stroke.We hypothesized that cerebellar stimulation was superior to vagus stimulation as the motor rehabilitation after stroke benefits from both side of cerebellum.

Study Overview

• Status: Recruiting
• Conditions: Stroke
• Intervention / Treatment: Device: Bilateral Cerebellar deep brain stimulation; Device: Unilateral Cerebellar deep brain stimulation; Device: Vagus Nerve Stimulation

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

Contacts and Locations

Study Locations

• China
  • Sichuan
    • Jinan, Sichuan, China, 250100
      • Recruiting
      • Chao Zhang
      • Contact: chao zhang; Phone Number: +8613969007232; 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 12-36 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
Active Comparator: Unilateral Cerebellar deep brain stimulation; Following enrollment, participants 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 DBS system, with the lead implanted in the DN contralateral to the stroke-affected cerebral hemisphere. 1 months later, DBS was activated unilaterally.	Device: Unilateral Cerebellar deep brain stimulation; Participants underwent stereotactic implantation of a single DBS lead in the area of the cerebellar DN contralateral to the lesioned cerebral hemisphere using a frame-based technique similar to that used in DBS for movement disorders. All participants received an 4-channel lead (Medtronic,3389）with electrode arrays up to 15.5 mm in length. Then unilateral stimulation was activated after 1 month post-DBS
Active Comparator: Bilateral Cerebellar deep brain stimulation; Following enrollment, participants 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 DBS system, with the lead implanted in the DN contralateral to the stroke-affected cerebral hemisphere. 1 months later, DBS was activated bilaterally.	Device: Bilateral Cerebellar deep brain stimulation; Participants underwent stereotactic implantation of a single DBS lead in the area of the cerebellar DN contralateral to the lesioned cerebral hemisphere using a frame-based technique similar to that used in DBS for movement disorders. All participants received an 4-channel lead (Medtronic,3389）with electrode arrays up to 15.5 mm in length. Then bilateral stimulation was activated after 1 month post-DBS
Experimental: Vagus Nerve Stimulation; Following enrollment, participants 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 unilaterally.	Device: Vagus Nerve Stimulation; 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 cerebellar DBS and 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 cerebellar DBS and 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 cerebellar DBS and 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 cerebellar DBS and 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 cerebellar DBS and 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 cerebellar DBS and 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
the Beck Depression Inventory or the Beck Anxiety Inventory between cerebellar DBS and VNS	The outcomes includes each participant's score of the Beck Depression Inventory or the Beck Anxiety Inventory for each monthly visit.	12 months after device implantation
nerve conduction velocity between cerebellar DBS and VNS	The outcomes includes each participant's nerve conduction velocity for each monthly visit recorded by flexible electrode.	12 months after device implantation
safety and feasibility of VNS and cerebellar DBS	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 (Actual): March 15, 2024
• Primary Completion (Estimated): June 7, 2025
• Study Completion (Estimated): March 7, 2026

Study Registration Dates

• First Submitted: February 5, 2024
• First Submitted That Met QC Criteria: March 4, 2024
• First Posted (Actual): March 12, 2024

Study Record Updates

• Last Update Posted (Actual): April 17, 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; Cerebellar Deep Brain Stimulation; 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: VNS or DBS for stroke

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Individual participant data (IPD) could be available to other researchers by request of email

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