Rehabilitation Paired with VNS for Motor Function Recovery

A Trial of Rehabilitation Paired with VNS for Motor Function Recovery in Post-ICH Patients (Recovery Study)

The goal of this clinical trial is to investigate the efficacy and safety of vagus nerve stimulation (VNS) combined with rehabilitation in improving upper extremity motor function after spontaneous intracerebral hemorrhage (ICH).

Researchers will evaluate the efficacy and safety of VNS by comparing the improvements of arm motor function post-ICH in the active VNS combined rehabilitation group with that in the sham VNS combined rehabilitation group (actual intensity 0 mA).

Participants in this study will undergo a surgical procedure to implant the VNS system and will subsequently recieve a 6 weeks in-clinic therapy, followed by an additional 6 weeks home exercise. During the final 6 weeks, participants will either recieve in-clinic therapy or maintain their home exercise, depending on their assigned group.

Study Overview

• Status: Not yet recruiting
• Conditions: Rehabilitation; Motor Function; Vagus Nerve Stimulation; Upper Extremity Injury; Spontaneous Intracerebral Hemorrhage
• Intervention / Treatment: Device: Active-VNS; Device: Sham VNS

Detailed Description

There are 6 follow-up timepoints in this trial:

1. Screening follow-up timepoint (V1): All participants will sign the informed consent form and receive pre-implant evaluation, including physical examination, brain magnetic resonance imaging, FMA-UE, WMFT, modified Ashworth scale, ect.
2. Surgery follow-up timepoint (V2): All participants will be implanted with the VNS system, including the G115R IPG and L312 lead.
3. Baseline follow-up timepoint (V3): There is a baseline evaluation 7 to 14 days after the surgery, then participants will be randomly assigned to VNS group or Control group.
4. Clinic rehabilitation follow-up timepoint (V4): Participants will receive standard clinic rehabilitation 3 days per week and lasting 6 weeks. Both active VNS group (VNS group) and sham VNS group (Control group) will receive rehabilitation. Participants will be evaluated at the last day of this follow-up timepoint.
5. Home exercise follow-up timepoint (V5): Participants will take standard home exercise everyday in 6 weeks. Both active VNS group (VNS group) and sham VNS group (Control group) will receive rehabilitation. At the last day, after evaluating, group assignment is unblinded.
6. Unmasking follow-up timepoint (V6): In this 6 weeks, all participants will receive active VNS. Participants in VNS group will still take standard home exercise, and participants in Control group will receive standard clinic rehabilitation again. Participants will be also evaluated at the last day of this follow-up timepoint.

• Study Type: Interventional
• Enrollment (Estimated): 10
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Fuxin Lin; Phone Number: 13600893154; Email: lfxstudy@126.com

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Age ≥22 years and <80 years, all gender is acceptable.
• History of unilateral supratentorial intracerebral hemorrhage ≥ 6 months but < 5 years.
• Upper Extremity motor section of the Fugl-Meyer Assessment score ≥20 and ≤50.
• Right- or left-sided weakness of upper extremity.
• Ability to communicate, understand, and give appropriate consent. Subjects can follow trial commands.
• Subjects have good compliance and can complete the visits after surgery.

Exclusion Criteria:

• History of ischemic stroke.
• Cerebral hemorrhage resulting from tumors, trauma, aneurysms, or hemorrhagic transformation of ischemic stroke.
• Presence of ongoing dysphagia or aspiration difficulties.
• Prior injury to vagus nerve, either bilateral or unilateral.
• Subject receiving medication that may significantly interfere with actions of VNS on neurotransmitter systems at study entry, clinic rehabilitation follow-up timepoint, or home rehabilitation follow-up timepoint, such as centrally acting cholinoceptor blockers, centrally acting adrenoceptor blockers, norepinephrine re-uptake inhibitors, etc.
• Botox injections within 4 weeks prior to enrollment through the unmasking follow-up timepoint (Visit 6).
• Severe spasticity of the upper extremity (Modified Ashworth ≥ 3).
• Significant sensory loss of the upper extremity (Upper Extremity sensory section of the Fugl-Meyer Assessment score < 6).
• Current requirement, or likely future requirement, of diathermy.
• Current use of any other stimulation device, such as a pacemaker or other neurostimulator.
• Pregnancy or plans to become pregnant or to breastfeed during the study period.
• Participated in any other clinical trials within the preceding 3 months.
• Not considered to be applicable by the investigator.

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: VNS group; Active VNS paired with rehabilitation Device: VNS A neuromodulation treatment that delivers electrical impulses to the brain via the vagus nerve. Other: Rehabilitation Rehabilitation movements to improve upper limb function after stroke.	Device: Active-VNS; A neuromodulation treatment that delivers electrical impulses to the brain via the vagus nerve.
Sham Comparator: Control group; Sham VNS paired with rehabilitation Device: Sham VNS A neuromodulation treatment that delivers electrical impulses to the brain via the vagus nerve, the actual intensity is 0 mA. Other: Rehabilitation Rehabilitation movements to improve upper limb function after stroke.	Device: Sham VNS; A neuromodulation treatment that delivers electrical impulses to the brain via the vagus nerve, the actual intensity is 0 mA.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Upper Extremity Motor Section of the Fugl-Meyer Assessment (FMA-UE) Average Change	The FMA-UE is a common scale used to measure motor impairment after a stroke. The range is 0 (more impairment) to 66 (no impairment). The FMA-UE will be analyzed for difference in average change at Clinic rehabilitation follow-up timepoint compared to Baseline follow-up timepoint (Difference in average change in FMA-UE from V3 to V4).	V4, 6 weeks after baseline follow-up timepoint

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Upper Extremity Motor Section of the Fugl-Meyer Assessment (FMA-UE) Response	The Upper Extremity Motor Section of the Fugl-Meyer Assessment (FMA-UE) Response is the percent of patients with a 6 point or greater improvement on the FMA-UE.	V4, 6 weeks after Baseline follow-up timepoint; V5, 6 weeks after Clinic rehabilitation follow-up timepoint
Upper Extremity Motor Section of the Fugl-Meyer Assessment (FMA-UE) Average Change	The FMA-UE is a common scale used to measure motor impairment after a stroke. The range is 0 (more impairment) to 66 (no impairment).	V5, 6 weeks after Clinic rehabilitation follow-up timepoint; V6, 6 weeks after Home exercise follow-up timepoint
Wolf Motor Function Test (WMFT) Average Change	The Wolf Motor Function Test (WMFT) is an assessment scale of upper extremity functional level after stroke. The functional assessment range is an average of 15 sub-items with a range from 0 to 5, with 0 (meaning did not attempt) to 5 (meaning normal).	V4, 6 weeks after Baseline follow-up timepoint; V5, 6 weeks after Clinic rehabilitation follow-up timepoint; V6, 6 weeks after Home exercise follow-up timepoint
Wolf Motor Function Test (WMFT) Response	Wolf Motor Function Test (WMFT) Response is the percent of patients with a 0.4 point or greater improvement on the WMFT.	V4, 6 weeks after Baseline follow-up timepoint; V5, 6 weeks after Clinic rehabilitation follow-up timepoint
EQ-5D-3L Average Change	The EQ-5D-3L is a general measure of health outcomes in any population. It is a self-report questionnaire which provides a simple descriptive profile and a single index value for health status.	V4, 6 weeks after Baseline follow-up timepoint; V5, 6 weeks after Clinic rehabilitation follow-up timepoint; V6, 6 weeks after Home exercise follow-up timepoint
Incidence of Adverse Events	The incidence of adverse events occurred during the clinical trial, whether or not related to the device.	V4, 6 weeks after Baseline follow-up timepoint; V5, 6 weeks after Clinic rehabilitation follow-up timepoint; V6, 6 weeks after Home exercise follow-up timepoint

Collaborators and Investigators

• Sponsor: First Affiliated Hospital of Fujian Medical University
• Collaborators: Beijing Pins Medical Co., Ltd
• Investigators: Principal Investigator: Fuxin Lin, First Affiliated Hospital of Fujian Medical University

Study record dates

Study Major Dates

• Study Start (Estimated): April 1, 2025
• Primary Completion (Estimated): March 31, 2027
• Study Completion (Estimated): December 30, 2027

Study Registration Dates

• First Submitted: March 19, 2025
• First Submitted That Met QC Criteria: March 19, 2025
• First Posted (Actual): March 25, 2025

Study Record Updates

• Last Update Posted (Estimated): March 26, 2025
• Last Update Submitted That Met QC Criteria: March 23, 2025
• Last Verified: February 1, 2025

More Information

Terms related to this study

• Keywords: Rehabilitation; Stroke; Neuromodulation; Randomized Controlled Trial; Vagus Nerve Stimulation; Upper Extremity Paresis; Hemorrhagic Stroke
• Additional Relevant MeSH Terms: Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Wounds and Injuries; Pathologic Processes; Intracranial Hemorrhages; Hemorrhage; Cerebral Hemorrhage; Arm Injuries
• Other Study ID Numbers: 82371466

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Deidentified case data are available from the authors upon reasonable request, after request in writing to the corresponding authors and after approval by the study committee and principal investigators from each site.

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