Deep brain stimulation versus vagus nerve stimulation for the motor function of poststroke hemiplegia: study protocol for a multicentre randomised controlled trial.

Publisher: BMJ Publishing Group Ltd Country of Publication: England NLM ID: 101552874 Publication Model: Electronic Cited Medium: Internet ISSN: 2044-6055 (Electronic) Linking ISSN: 20446055 NLM ISO Abbreviation: BMJ Open Subsets: MEDLINE

Original Publication: [London] : BMJ Publishing Group Ltd, 2011-

Hemiplegia*/etiology ; Hemiplegia*/therapy ; Hemiplegia*/rehabilitation ; Vagus Nerve Stimulation*/methods ; Deep Brain Stimulation*/methods ; Stroke*/complications ; Stroke*/therapy; Humans ; Double-Blind Method ; Male ; Female ; Randomized Controlled Trials as Topic ; Middle Aged ; Quality of Life ; Aged ; Adult ; Stroke Rehabilitation/methods ; Treatment Outcome ; Multicenter Studies as Topic ; Recovery of Function

Introduction: Deep brain stimulation (DBS) and vagus nerve stimulation (VNS) can improve motor function in patients with poststroke hemiplegia. No comparison study exists.
Methods and Analysis: This is a randomised, double-blind, controlled clinical trial involving 64 patients who had their first stroke at least 6 months ago and are experiencing poststroke limb dysfunction. These patients must receive necessary support at home and consent to participate. The aim is to evaluate the effectiveness and safety of DBS and VNS therapies. Patients are excluded if they have implantable devices that are sensitive to electrical currents, severe abnormalities in their lower limbs or are unable to comply with the trial procedures. The study has two parallel, distinct treatment arms: the Stimulation Group and the Sham Group. Initially, the Stimulation Group will undergo immediate electrical stimulation postsurgery, while the Sham Group will receive non-stimulation 1 month later. After 3 months, these groups will swap treatments, with the Stimulation Group discontinuing stimulation and the Sham Group initiating stimulation. Six months later, both groups will resume active stimulation. Our primary outcomes will meticulously assess motor function improvements, using the Fugl-Meyer Assessment, and safety, monitored by tracking adverse reaction rates. Furthermore, we will gain a comprehensive view of patient outcomes by evaluating secondary measures, including clinical improvement (National Institutes of Health Stroke Scale), surgical complications/side effects, quality of life (36-item Short Form Questionnaire) and mental health status (Hamilton Anxiety Rating Scale/Hamilton Depression Rating Scale). To ensure a thorough understanding of the long-term effects, we will conduct follow-ups at 9 and 12 months postsurgery, with additional long-term assessments at 15 and 18 months. These follow-ups will assess the sustained performance and durability of the treatment effects. The statistical analysis will uncover the optimal treatment strategy for poststroke hemiplegia, providing valuable insights for clinicians and patients alike.
Ethics and Dissemination: This study was reviewed and approved by the Ethical Committee of Chinese PLA General Hospital (S2022-789-01). The findings will be submitted for publication in peer-reviewed journals with online accessibility, ensuring adherence to the conventional scientific publishing process while clarifying how the research outcomes will be disseminated and accessed.
Trial Registration Number: NCT06121947.
Competing Interests: Competing interests: None declared.
(© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Stroke. 2018 Nov;49(11):2789-2792. (PMID: 30355189)
Neuropsychopharmacology. 2020 May;45(6):1018-1025. (PMID: 32053828)
J Clin Epidemiol. 2016 Aug;76:175-82. (PMID: 26964707)
Stroke. 2016 Jan;47(1):143-50. (PMID: 26645257)
JAMA Psychiatry. 2023 Aug 1;80(8):842-847. (PMID: 37314797)
Proc Natl Acad Sci U S A. 2021 Oct 26;118(43):. (PMID: 34670837)
Nature. 2018 Jan 25;553(7689):455-460. (PMID: 29342142)
Clin Rehabil. 2005 Oct;19(7):760-6. (PMID: 16250195)
Exp Neurol. 2022 Jan;347:113884. (PMID: 34624326)
Neurosurg Rev. 2015 Oct;38(4):753-63. (PMID: 25990341)
Int J Mol Sci. 2019 May 11;20(9):. (PMID: 31083528)
Lancet Neurol. 2015 Feb;14(2):224-34. (PMID: 25772900)
BMJ Open. 2023 Oct 13;13(10):e073425. (PMID: 37832982)
Neuropsychiatr Dis Treat. 2021 Mar 25;17:905-913. (PMID: 33790559)
Appl Neurophysiol. 1982;45(3):209-17. (PMID: 6977333)
J Neurophysiol. 2017 Aug 1;118(2):1151-1163. (PMID: 28566461)
Brain. 2018 Aug 1;141(8):2445-2456. (PMID: 29982424)
J Mov Disord. 2017 Jan;10(1):64-66. (PMID: 28122425)
SAGE Open Med. 2016 Oct 04;4:2050312116671725. (PMID: 27757230)
Neurosurgery. 2018 Nov 1;83(5):1057-1067. (PMID: 29029200)
Neuromodulation. 2021 Feb;24(2):361-372. (PMID: 32620052)
Brain Res Bull. 2018 May;139:38-47. (PMID: 29432795)
Stat Med. 2021 Aug 30;40(19):4230-4251. (PMID: 34031906)
Neurorehabil Neural Repair. 2020 Jul;34(7):609-615. (PMID: 32476617)
Brain Struct Funct. 2022 Dec;227(9):3173-3187. (PMID: 35881254)
Mov Disord. 2013 Sep;28(10):1456-7. (PMID: 23426802)
Continuum (Minneap Minn). 2017 Feb;23(1, Cerebrovascular Disease):15-39. (PMID: 28157742)
Brain Nerve. 2020 Apr;72(4):311-321. (PMID: 32284456)
Int J Stroke. 2014 Apr;9(3):313-20. (PMID: 23227818)
J Stroke Cerebrovasc Dis. 2020 Jan;29(1):104463. (PMID: 31740027)
Stereotact Funct Neurosurg. 2013;91(4):243-7. (PMID: 23549056)
Eur Stroke J. 2019 Dec;4(4):363-377. (PMID: 31903435)
Eur J Phys Rehabil Med. 2019 Dec;55(6):754-760. (PMID: 30868834)
Lancet. 2019 Jul 6;394(10192):51-62. (PMID: 31128926)
Can J Neurol Sci. 2016 Jan;43(1):120-6. (PMID: 26786642)
Nat Med. 2023 Sep;29(9):2366-2374. (PMID: 37580534)
Neurosurgery. 2013 Aug;73(2):344-53; discussion 353. (PMID: 23670034)
J Stroke Cerebrovasc Dis. 2016 Dec;25(12):2953-2957. (PMID: 27693107)
Neurosurg Focus. 2018 Aug;45(2):E13. (PMID: 30064319)
BMJ Open. 2021 Sep 30;11(9):e047670. (PMID: 34593490)
J Neurosurg. 2022 Oct 28;138(6):1688-1701. (PMID: 36308482)
Curr Biol. 2018 Mar 19;28(6):884-901.e3. (PMID: 29526593)
Brain Stimul. 2018 Jan - Feb;11(1):3-28. (PMID: 29089234)
Int J Mol Sci. 2021 Jan 27;22(3):. (PMID: 33514001)
Lancet Neurol. 2023 Dec;22(12):1160-1206. (PMID: 37827183)
Brain Res Bull. 2016 Oct;127:111-118. (PMID: 27614236)
J Clin Epidemiol. 2021 Jul;135:79-89. (PMID: 33596458)
BMJ. 2020 Mar 18;368:m441. (PMID: 32188600)
Arch Phys Med Rehabil. 1999 Sep;80(9):1013-6. (PMID: 10489001)
Front Neural Circuits. 2021 Apr 09;15:639900. (PMID: 33897379)
Curr Neuropharmacol. 2024;22(9):1454-1472. (PMID: 37559244)
Pilot Feasibility Stud. 2021 Jun 2;7(1):117. (PMID: 34078477)
Brain. 2014 Jun;137(Pt 6):1716-32. (PMID: 24736305)
Science. 2016 Sep 23;353(6306):1393-1398. (PMID: 27562954)
J Cereb Blood Flow Metab. 2022 Jan;42(1):213-215. (PMID: 34670442)
Front Neurol. 2014 Dec 04;5:243. (PMID: 25538673)
Sci Rep. 2017 Jun 01;7:46612. (PMID: 28569261)
Int J Mol Sci. 2022 Dec 14;23(24):. (PMID: 36555504)
Stat Med. 2016 Jan 30;35(2):214-26. (PMID: 26553135)
Stroke. 2018 Sep;49(9):2138-2146. (PMID: 30354990)
Neuron. 2018 Oct 24;100(2):361-374. (PMID: 30359602)
J Headache Pain. 2022 Jan 21;23(1):12. (PMID: 35062860)
J Mol Neurosci. 2019 Feb;67(2):217-226. (PMID: 30484061)
Curr Phys Med Rehabil Rep. 2020 Jun;8(2):57-63. (PMID: 33585074)
Brain Stimul. 2021 May-Jun;14(3):467-476. (PMID: 33652130)
Tremor Other Hyperkinet Mov (N Y). 2014 Feb 04;4:. (PMID: 24587970)
Nature. 2022 Nov;611(7936):540-547. (PMID: 36352232)
Front Neurosci. 2020 Apr 28;14:284. (PMID: 32410932)
Neurol India. 2021 Mar-Apr;69(2):272-283. (PMID: 33904435)
Stat Med. 2021 Jan 15;40(1):133-146. (PMID: 33150684)
Lancet Neurol. 2020 Aug;19(8):651-660. (PMID: 32702334)
Curr Biol. 2020 Mar 9;30(5):R229-R232. (PMID: 32155428)
Commun Biol. 2021 Jan 27;4(1):125. (PMID: 33504896)
Sci Rep. 2017 Nov 27;7(1):16343. (PMID: 29180821)
J Neurosci. 2022 Jun 29;42(26):5186-5197. (PMID: 35610051)
Neuromodulation. 2021 Feb;24(2):392-399. (PMID: 33389771)
Brain. 2016 Apr;139(Pt 4):1200-10. (PMID: 26921616)
Neurosurgery. 2019 Feb 1;84(2):506-518. (PMID: 29846707)
Neurotherapeutics. 2017 Jul;14(3):716-727. (PMID: 28585221)
Neurotherapeutics. 2014 Jul;11(3):572-82. (PMID: 24353109)
Ann Neurol. 2017 Nov;82(5):828-840. (PMID: 29059697)
Int J Mol Sci. 2022 Jul 28;23(15):. (PMID: 35955498)
Lancet Neurol. 2021 Oct;20(10):795-820. (PMID: 34487721)
Neuroimage. 2019 Jan 1;184:293-316. (PMID: 30179717)
Expert Rev Neurother. 2017 May;17(5):509-519. (PMID: 27978768)
Front Neurosci. 2019 Mar 29;13:280. (PMID: 30983963)

Keywords: electric stimulation therapy; neurosurgery; physical therapy modalities; research design; stroke; stroke medicine

ClinicalTrials.gov NCT06121947

Date Created: 20241009 Date Completed: 20241009 Latest Revision: 20241018

20250114

PMC11474896

10.1136/bmjopen-2024-086098

39384245