A Trial of Rehabilitation Paired with VNS for Motor Function in Patients with Stroke (Repair Study)

Официальное название

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)

Обзор

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.

Подробное описание

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.

Вмешательства

• Устройство VNS
  An neuromodulation treatment that delivers electrical impulses to the brain via the vagus nerve.
• Устройство Sham VNS
  An neuromodulation treatment that delivers electrical impulses to the brain via the vagus nerve, the actual intensity is 0 mA.
• Другое Rehabilitation
  Rehabilitation movements to improve upper limb function after stroke.

Первичные конечные точки

• Upper Extremity Motor Section of the Fugl-Meyer Assessment (FMA-UE) Average Change [Срок оценки: V4, 6 weeks after Baseline follow-up timepoint]

Вторичные конечные точки (10)

• Upper Extremity Motor Section of the Fugl-Meyer Assessment (FMA-UE) Response [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: 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 [Срок оценки: V4, 6 weeks after Baseline follow-up timepoint; V5, 6 weeks after Clinic rehabilitation follow-up timepoint]
• Beck Depression Inventory (BDI) Average Change [Срок оценки: V6, 6 weeks after Home exercise follow-up timepoint]
• Montreal Cognitive Assessment (MoCA) Average Change [Срок оценки: 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]
• Motor Activity Log (MAL) Average Change [Срок оценки: 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]
• Stroke impact scale (SIS) Average Change [Срок оценки: 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]
• EQ-5D-3L Average Change [Срок оценки: 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 [Срок оценки: 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]

Критерии участия

Критерии включения

• Age ≥22 years and <80 years, all gender is acceptable.
• History of unilateral supratentorial ischemic stroke ≥ 9 months but < 10 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.

Критерии исключения

• History of hemorrhagic 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).
• Severe depression (Beck Depression Scale > 29).
• 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.

Критерии приведены из реестра в оригинале (на английском). Окончательную оценку соответствия проводит исследовательский центр.

Здоровые добровольцы: Нет

Дизайн исследования

Распределение

Рандомизированное

Модель

Параллельные группы

Маскирование

Четверное слепое

Основная цель

Лечение

Центры проведения

Китай · 16 центров

• The First Affiliated Hospital of USTC — Хэфэй
• Beijing Tiantan Hospital, Capital Medical University — Пекин
• Chinese People's Liberation Army General Hospital — Пекин
• The Xin Qiao Hospital of Army Medical University — Чунцин
• The First Affiliated Hospital of Fujian Medical University — Фучжоу
• Zhujiang Hospital of Southern Medical University — Гуанчжоу
• Jiangbin Hospital of Guangxi Zhuang Autonomous Region — Nanning
• Tongji Hospital Tongji Medical College of HUST — Ухань
• … и ещё 8 центров

Публикации

• 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 PMID 33894832
• Kimberley TJ, Prudente CN, Engineer ND, Pierce D, Tarver B, Cramer SC, Dickie DA, Dawson J. Study protocol for a pivotal randomised study assessing vagus nerve stimulation during rehabilitation for improved upper limb motor function after stroke. Eur Stroke J. 2019 Dec;4(4):363-377. doi: 10.1177/2396987319855306. Epub 2019 Jun 17. PMID 31903435
• Dawson J, Engineer ND, Prudente CN, Pierce D, Francisco G, Yozbatiran N, Tarver WB, Casavant R, Kline DK, Cramer SC, Van de Winckel A, Kimberley TJ. Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Stroke: One-Year Follow-up. Neurorehabil Neural Repair. 2020 Jul;34(7):609-615. doi: 10.1177/1545968320924361. Epub 2020 Jun 1. PMID 32476617
• Dickie DA, Kimberley TJ, Pierce D, Engineer N, Tarver WB, Dawson J. An Exploratory Study of Predictors of Response to Vagus Nerve Stimulation Paired with Upper-Limb Rehabilitation After Ischemic Stroke. Sci Rep. 2019 Nov 4;9(1):15902. doi: 10.1038/s41598-019-52092-x. PMID 31685853
• Dawson J, Engineer ND, Cramer SC, Wolf SL, Ali R, O'Dell MW, Pierce D, Prudente CN, Redgrave J, Feng W, Liu CY, Francisco GE, Brown BL, Dixit A, Alexander J, DeMark L, Krishna V, Kautz SA, Majid A, Tarver B, Turner DL, Kimberley TJ. Vagus Nerve Stimulation Paired With Rehabilitation for Upper Limb Motor Impairment and Function After Chronic Ischemic Stroke: Subgroup Analysis of the Randomized, Bli PMID 36226541
• Dawson J, Pierce D, Dixit A, Kimberley TJ, Robertson M, Tarver B, Hilmi O, McLean J, Forbes K, Kilgard MP, Rennaker RL, Cramer SC, Walters M, Engineer N. Safety, Feasibility, and Efficacy of Vagus Nerve Stimulation Paired With Upper-Limb Rehabilitation After Ischemic Stroke. Stroke. 2016 Jan;47(1):143-50. doi: 10.1161/STROKEAHA.115.010477. Epub 2015 Dec 8. PMID 26645257
• Hays SA, Khodaparast N, Hulsey DR, Ruiz A, Sloan AM, Rennaker RL 2nd, Kilgard MP. Vagus nerve stimulation during rehabilitative training improves functional recovery after intracerebral hemorrhage. Stroke. 2014 Oct;45(10):3097-100. doi: 10.1161/STROKEAHA.114.006654. Epub 2014 Aug 21. PMID 25147331
• Hays SA, Khodaparast N, Sloan AM, Fayyaz T, Hulsey DR, Ruiz AD, Pantoja M, Kilgard MP, Rennaker RL 2nd. The bradykinesia assessment task: an automated method to measure forelimb speed in rodents. J Neurosci Methods. 2013 Mar 30;214(1):52-61. doi: 10.1016/j.jneumeth.2012.12.022. Epub 2013 Jan 23. PMID 23353133

Идентификаторы

NCT: NCT06722677 · G115R&PINS-C2-01-53

Первоисточники (государственные реестры)

• ClinicalTrials.gov (NIH, США)

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