Clinical trial NCT06722677: A Trial of Rehabilitation Paired with VNS for Motor Function in Patients with Stroke (Repair Study)
Official title: A Multi-Center, Triple-Blind, Randomized, Sham-Controlled Trial Assessing the Efficacy and Safety of Rehabilitation Paired with Vagus Nerve Stimulation for Upper Extremity Motor Function in Patients with Ischemic Stroke (Repair Study)
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: NA
Conditions: Ischemic Stroke
Upper Extremity Paresis
Keywords: Stroke
Ischemic Stroke
Paresis
Upper Extremity Paresis
Vagus Nerve Stimulation
Neuromodulation
Randomized Controlled Trial
Rehabilitation
Lead sponsor: Beijing Pins Medical Co., Ltd
Sponsor class: INDUSTRY
First posted: 2024-12-09
Enrollment: 99
Sex: ALL
Minimum age (years): 22
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The goal of this clinical trial is to investigate the efficacy and safety of vagus nerve stimulation (VNS) paired with rehabilitation for enhancing upper extremity motor function after ischemic stroke.

Researchers will compare the outcomes of active VNS paired with rehabilitation against sham VNS (the actual intensity is 0 mA) also paired with rehabilitation, in order to assess improvements in arm motor function post-stroke.

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.

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 sacle, BDI, 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. The randomization will be stratified by baseline FMA-UE (20 to 35, 36 to 50), age (\<50, ≥50) and research center (south centers, north centers).
4. Clinic rehabilitation follow-up timepoint (V4): Participants will receive standard clinic rehabilitation 3 days per week and lasting 6 weeks. Active VNS (VNS group) or sham VNS (Control group) will be paired with 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. Active VNS (VNS group) or sham VNS (Control group) will be paired with 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.

Eligibility criteria: Inclusion Criteria:

1. Age ≥22 years and \<80 years, all gender is acceptable.
2. History of unilateral supratentorial ischemic stroke ≥ 9 months but \< 10 years.
3. Upper Extremity motor section of the Fugl-Meyer Assessment score ≥20 and ≤50.
4. Right- or left-sided weakness of upper extremity.
5. Ability to communicate, understand, and give appropriate consent. Subjects can follow trial commands.
6. Subjects have good compliance and can complete the visits after surgery.

Exclusion Criteria:

1. History of hemorrhagic stroke.
2. Presence of ongoing dysphagia or aspiration difficulties.
3. Prior injury to vagus nerve, either bilateral or unilateral.
4. 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.
5. Botox injections within 4 weeks prior to enrollment through the unmasking follow-up timepoint (Visit 6).
6. Severe spasticity of the upper extremity (Modified Ashworth ≥ 3).
7. Significant sensory loss of the upper extremity (Upper Extremity sensory section of the Fugl-Meyer Assessment score \< 6).
8. Severe depression (Beck Depression Scale \> 29).
9. Current requirement, or likely future requirement, of diathermy.
10. Current use of any other stimulation device, such as a pacemaker or other neurostimulator.
11. Pregnancy or plans to become pregnant or to breastfeed during the study period.
12. Participated in any other clinical trials within the preceding 3 months.
13. Not considered to be applicable by the investigator.

Primary outcomes:
measure: Upper Extremity Motor Section of the Fugl-Meyer Assessment (FMA-UE) Average Change
timeFrame: V4, 6 weeks after Baseline follow-up timepoint
Secondary outcomes:
measure: Upper Extremity Motor Section of the Fugl-Meyer Assessment (FMA-UE) Response
timeFrame: V4, 6 weeks after Baseline follow-up timepoint; V5, 6 weeks after Clinic rehabilitation follow-up timepoint
measure: Upper Extremity Motor Section of the Fugl-Meyer Assessment (FMA-UE) Average Change
timeFrame: V5, 6 weeks after Clinic rehabilitation follow-up timepoint; V6, 6 weeks after Home exercise follow-up timepoint
measure: Wolf Motor Function Test (WMFT) Average Change
timeFrame: 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
measure: Wolf Motor Function Test (WMFT) Response
timeFrame: V4, 6 weeks after Baseline follow-up timepoint; V5, 6 weeks after Clinic rehabilitation follow-up timepoint
measure: Beck Depression Inventory (BDI) Average Change
timeFrame: V6, 6 weeks after Home exercise follow-up timepoint
measure: Montreal Cognitive Assessment (MoCA) Average Change
timeFrame: 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
measure: Motor Activity Log (MAL) Average Change
timeFrame: 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
measure: Stroke impact scale (SIS) Average Change
timeFrame: 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
measure: EQ-5D-3L Average Change
timeFrame: 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
measure: Incidence of Adverse Events
timeFrame: 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
Other outcomes:
Locations:
city: Hefei
country: China
facility: The First Affiliated Hospital of USTC
state: Anhui
city: Beijing
country: China
facility: Beijing Tiantan Hospital, Capital Medical University
state: Beijing
city: Beijing
country: China
facility: Chinese People's Liberation Army General Hospital
state: Beijing
city: Chongqing
country: China
facility: The Xin Qiao Hospital of Army Medical University
state: Chongqing
city: Fuzhou
country: China
facility: The First Affiliated Hospital of Fujian Medical University
state: Fujian
city: Guangzhou
country: China
facility: Zhujiang Hospital of Southern Medical University
state: Guangdong
city: Nanning
country: China
facility: Jiangbin Hospital of Guangxi Zhuang Autonomous Region
state: Guangxi
city: Wuhan
country: China
facility: Tongji Hospital Tongji Medical College of HUST
state: Hubei
city: Changsha
country: China
facility: Brain Hospital of Hunan Province The Second People's Hospital of Hunan Province
state: Hunan
city: Nanjing
country: China
facility: Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing university Medical School
state: Jiangsu
city: Nanchang
country: China
facility: The First Affiliated Hospital of Nanchang University
state: Jiangxi
city: Changchun
country: China
facility: The First Bethune Hospital of Jilin University
state: Jilin
city: Jinan
country: China
facility: Qilu Hospital of Shandong University
state: Shandong
city: Shanghai
country: China
facility: Huashan Hospital, Fudan University
state: Shanghai
city: Chengdu
country: China
facility: West China Hospital, Sichuan University
state: Sichuan
city: Kunming
country: China
facility: The First Affiliated Hospital of Kunming Medical University
state: Yunnan
Study officials:
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