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

NCT06722677 | Recruiting DMC

• 1 other identifier: G115R&PINS-C2-01-53
• Study Type: interventional
• Target: 99
• Locations: 1 country
• Sites: 16

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.

Conditions

Ischemic Stroke; Upper Extremity Paresis

Keywords

Stroke; Ischemic Stroke; Paresis; Upper Extremity Paresis; Vagus Nerve Stimulation; Neuromodulation; Randomized Controlled Trial; Rehabilitation

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (10)

• Upper Extremity Motor Section of the Fugl-Meyer Assessment (FMA-UE) Response

  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

  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

  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

  V4, 6 weeks after Baseline follow-up timepoint; V5, 6 weeks after Clinic rehabilitation follow-up timepoint

• Beck Depression Inventory (BDI) Average Change

  V6, 6 weeks after Home exercise follow-up timepoint

Study Arms (2)

VNS group

EXPERIMENTAL

Active VNS paired with rehabilitation

Device: VNS; Other: Rehabilitation

Control group

ACTIVE COMPARATOR

Sham VNS paired with rehabilitation

Device: Sham VNS; Other: Rehabilitation

Interventions

VNS DEVICE

An neuromodulation treatment that delivers electrical impulses to the brain via the vagus nerve.

VNS group

Sham VNS DEVICE

An neuromodulation treatment that delivers electrical impulses to the brain via the vagus nerve, the actual intensity is 0 mA.

Control group

Rehabilitation OTHER

Rehabilitation movements to improve upper limb function after stroke.

Control group; VNS group

Eligibility Criteria

• Age: 22 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Beijing Pins Medical Co., Ltd: lead

Study Sites (16)

The First Affiliated Hospital of USTC

Hefei, Anhui, 230022, China

NOT YET RECRUITING

Beijing Tiantan Hospital, Capital Medical University

Beijing, Beijing Municipality, 100000, China

RECRUITING

Chinese People's Liberation Army General Hospital

Beijing, Beijing Municipality, 100039, China

NOT YET RECRUITING

The Xin Qiao Hospital of Army Medical University

Chongqing, Chongqing Municipality, 400037, China

NOT YET RECRUITING

The First Affiliated Hospital of Fujian Medical University

Fuzhou, Fujian, 350004, China

RECRUITING

Zhujiang Hospital of Southern Medical University

Guangzhou, Guangdong, 510260, China

RECRUITING

Jiangbin Hospital of Guangxi Zhuang Autonomous Region

Nanning, Guangxi, 530012, China

RECRUITING

Tongji Hospital Tongji Medical College of HUST

Wuhan, Hubei, 430030, China

RECRUITING

Brain Hospital of Hunan Province The Second People's Hospital of Hunan Province

Changsha, Hunan, 410000, China

NOT YET RECRUITING

Nanjing Drum Tower Hospital The Affiliated Hospital of Nanjing university Medical School

Nanjing, Jiangsu, 210008, China

NOT YET RECRUITING

The First Affiliated Hospital of Nanchang University

Nanchang, Jiangxi, 330006, China

NOT YET RECRUITING

The First Bethune Hospital of Jilin University

Changchun, Jilin, 130021, China

RECRUITING

Qilu Hospital of Shandong University

Jinan, Shandong, 250012, China

NOT YET RECRUITING

Huashan Hospital, Fudan University

Shanghai, Shanghai Municipality, 200040, China

RECRUITING

West China Hospital, Sichuan University

Chengdu, Sichuan, 618099, China

NOT YET RECRUITING

The First Affiliated Hospital of Kunming Medical University

Kunming, Yunnan, 650032, China

RECRUITING

Related Publications (19)

• 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 Apr 24;397(10284):1545-1553. doi: 10.1016/S0140-6736(21)00475-X.

  PMID: 33894832 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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, Blinded, Pivotal, VNS-REHAB Device Trial. Neurorehabil Neural Repair. 2023 Jun;37(6):367-373. doi: 10.1177/15459683221129274. Epub 2022 Oct 13.

  PMID: 36226541 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• 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 BACKGROUND

• Khodaparast N, Kilgard MP, Casavant R, Ruiz A, Qureshi I, Ganzer PD, Rennaker RL 2nd, Hays SA. Vagus Nerve Stimulation During Rehabilitative Training Improves Forelimb Recovery After Chronic Ischemic Stroke in Rats. Neurorehabil Neural Repair. 2016 Aug;30(7):676-84. doi: 10.1177/1545968315616494. Epub 2015 Nov 4.

  PMID: 26542082 BACKGROUND

• Khodaparast N, Hays SA, Sloan AM, Hulsey DR, Ruiz A, Pantoja M, Rennaker RL 2nd, Kilgard MP. Vagus nerve stimulation during rehabilitative training improves forelimb strength following ischemic stroke. Neurobiol Dis. 2013 Dec;60:80-8. doi: 10.1016/j.nbd.2013.08.002. Epub 2013 Aug 15.

  PMID: 23954448 BACKGROUND

• Elsner B, Kugler J, Pohl M, Mehrholz J. Transcranial direct current stimulation (tDCS) for improving function and activities of daily living in patients after stroke. Cochrane Database Syst Rev. 2013 Nov 15;(11):CD009645. doi: 10.1002/14651858.CD009645.pub2.

  PMID: 24234980 BACKGROUND

• Plow EB, Carey JR, Nudo RJ, Pascual-Leone A. Invasive cortical stimulation to promote recovery of function after stroke: a critical appraisal. Stroke. 2009 May;40(5):1926-31. doi: 10.1161/STROKEAHA.108.540823. Epub 2009 Apr 9.

  PMID: 19359643 BACKGROUND

• Bolognini N, Pascual-Leone A, Fregni F. Using non-invasive brain stimulation to augment motor training-induced plasticity. J Neuroeng Rehabil. 2009 Mar 17;6:8. doi: 10.1186/1743-0003-6-8.

  PMID: 19292910 BACKGROUND

• Adkins DL, Hsu JE, Jones TA. Motor cortical stimulation promotes synaptic plasticity and behavioral improvements following sensorimotor cortex lesions. Exp Neurol. 2008 Jul;212(1):14-28. doi: 10.1016/j.expneurol.2008.01.031. Epub 2008 Feb 20.

  PMID: 18448100 BACKGROUND

• Barbay S, Nudo RJ. The effects of amphetamine on recovery of function in animal models of cerebral injury: a critical appraisal. NeuroRehabilitation. 2009;25(1):5-17. doi: 10.3233/NRE-2009-0495.

  PMID: 19713615 BACKGROUND

• Walker-Batson D, Curtis S, Natarajan R, Ford J, Dronkers N, Salmeron E, Lai J, Unwin DH. A double-blind, placebo-controlled study of the use of amphetamine in the treatment of aphasia. Stroke. 2001 Sep;32(9):2093-8. doi: 10.1161/hs0901.095720.

  PMID: 11546902 BACKGROUND

• Sawaki L, Butler AJ, Leng X, Wassenaar PA, Mohammad YM, Blanton S, Sathian K, Nichols-Larsen DS, Wolf SL, Good DC, Wittenberg GF. Constraint-induced movement therapy results in increased motor map area in subjects 3 to 9 months after stroke. Neurorehabil Neural Repair. 2008 Sep-Oct;22(5):505-13. doi: 10.1177/1545968308317531.

  PMID: 18780885 BACKGROUND

• Takahashi CD, Der-Yeghiaian L, Le V, Motiwala RR, Cramer SC. Robot-based hand motor therapy after stroke. Brain. 2008 Feb;131(Pt 2):425-37. doi: 10.1093/brain/awm311. Epub 2007 Dec 20.

  PMID: 18156154 BACKGROUND

• Zhang T, Zhao J, Li X, Bai Y, Wang B, Qu Y, Li B, Zhao S; Chinese Stroke Association Stroke Council Guideline Writing Committee. Chinese Stroke Association guidelines for clinical management of cerebrovascular disorders: executive summary and 2019 update of clinical management of stroke rehabilitation. Stroke Vasc Neurol. 2020 Sep;5(3):250-259. doi: 10.1136/svn-2019-000321. Epub 2020 Jun 28.

  PMID: 32595138 BACKGROUND

MeSH Terms

Conditions

Ischemic Stroke; Paresis; Stroke

Interventions

Rehabilitation

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Aftercare; Continuity of Patient Care; Patient Care; Therapeutics; Health Services; Health Care Facilities Workforce and Services

Central Study Contacts

Jianguang Sun

CONTACT

010-60736388; sunjianguang@pinsmedical.com

Baichuan He

CONTACT

18310971061; hebaichuan@pinsmedical.com

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: The device can be set as active VNS or sham VNS (the actual intensity is 0 mA). An unmasking programmer not involved in treatments or assessments will be messaged the group of the participant and set appropriate stimulation setting at baseline follow-up timepoint. Other masking researchers, including therapists and assessors, as well as the participant will not know the stimulation setting.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 10, 2024
• First Posted: December 9, 2024
• Study Start: November 19, 2024
• Primary Completion: August 1, 2025
• Study Completion: November 1, 2025
• Last Updated: December 10, 2024

Record last verified: 2024-12

Locations

CN (16)