Temporal Interference Stimulation for Upper-Limb Motor Recovery in Early Subacute Stroke (TIMES)
Effects of Transcranial Temporal Interference Stimulation on Upper-Limb Motor Recovery in Early Subacute Ischemic Stroke: A Randomized, Double-Blind, Sham-Controlled Pilot Trial
This study aims to test whether transcranial temporal interference stimulation (tTIs) can improve upper limb motor function in patients in the early subacute stage after acute ischemic stroke. Participants will be randomly assigned to receive either active tTIs treatment or sham stimulation. All subjects will receive routine rehabilitation. The treatment will be given once daily for 20 consecutive days. Researchers will assess upper limb motor function before treatment, during the intervention and after the treatment course to compare the effect between the two groups. Safety will also be monitored throughout the study.
Visão geral do estudo
Status
Condições
Descrição detalhada
This prospective, two-center, randomized, double-blind, parallel-group, exploratory pilot randomized controlled trial will enroll 60 right-handed patients with first-ever unilateral anterior circulation acute ischemic stroke in the early subacute phase (7 days to 3 months after stroke onset). All participants will have received reperfusion therapy and exhibit upper-limb motor impairment, defined as a Fugl-Meyer Assessment of the Upper Extremity (FMA-UE) score of ≤42. Participants will be randomly assigned in a 1:1 ratio to either the active tTIS group or the sham-stimulation group.All participants will receive standard rehabilitation therapy once daily for 20 consecutive days. In addition to routine rehabilitation, participants in the active tTIS group will receive active stimulation targeting the cerebellar dentate nucleus. Participants in the sham group will undergo an identical setup, including EEG cap placement, but will receive sham stimulation without effective amplitude-modulated output. Each stimulation session will last 20 minutes. Participants and outcome assessors will be blinded to group allocation, whereas the treatment operator will remain unblinded. Blinding will be maintained until the database is locked.
Assessments will be conducted at baseline, immediately before and after the first intervention session, on days 7 and 14, after completion of the 20-session intervention, and at the 3-month follow-up. Clinical assessments, multimodal magnetic resonance imaging (MRI), electroencephalography (EEG), and transcranial magnetic stimulation (TMS) examinations will be performed at prespecified time points to characterize changes in motor function, brain structural and functional connectivity, and cortical excitability. Adverse events will be systematically recorded and monitored throughout the trial.
This study aims to investigate the safety and feasibility of cerebellar dentate nucleus-targeted tTIS as an adjunct to routine rehabilitation and to obtain preliminary evidence of its efficacy in improving upper-limb motor function in patients with acute ischemic stroke during the early subacute phase. In addition, multimodal neuroimaging and neurophysiological assessments will be used to explore the potential neural mechanisms underlying tTIS-induced motor recovery.
Tipo de estudo
Inscrição (Estimado)
Estágio
- Não aplicável
Contactos e Locais
Contato de estudo
- Nome: Cong Fu
- Número de telefone: 010-83199060
- E-mail: fucong666@yeah.net
Locais de estudo
-
-
-
Beijing, China, 100053
- Xuanwu Hospital, Capital Medical University
-
Investigador principal:
- Liqun Jiao
-
Contato:
- Cong Fu
- Número de telefone: 010-83199060
- E-mail: fucong666@yeah.net
-
-
Critérios de participação
Critérios de elegibilidade
Idades elegíveis para estudo
Aceita Voluntários Saudáveis
Gêneros Elegíveis para o Estudo
Descrição
Inclusion Criteria:
- First-ever ischemic stroke occurring 7 days to 3 months before enrollment.
- Unilateral anterior-circulation ischemic stroke confirmed by CT or MRI.
- Receipt of reperfusion therapy.
- Age 18-80 years.
- Upper-limb motor impairment, defined as an FMA-UE score of ≤42.
- Right-handedness, as determined by the Edinburgh Handedness Inventory.
- Ability to understand and communicate adequately, willingness to participate, and provision of written informed consent.
Exclusion Criteria:
- Previous history of stroke, either ischemic or hemorrhagic.
- Severe cognitive impairment or psychiatric symptoms.
- Bilateral brain lesions or other neurological disorders, including Parkinson's disease, epilepsy, or brain tumors.
- Severe cardiac, pulmonary, hepatic, renal, or other major organ dysfunction.
- Skull defects.
- Increased intracranial pressure.
- Contraindications to MRI, including incompatible intracranial or external metal objects or implanted devices such as pacemakers or infusion pumps.
- Current participation in another clinical trial.
- Inability to complete the treatment or follow-up procedures, poor adherence, or adverse reactions to electrical stimulation that prevent continued participation.
- Pregnancy or breastfeeding.
Plano de estudo
Como o estudo é projetado?
Detalhes do projeto
- Finalidade Principal: Tratamento
- Alocação: Randomizado
- Modelo Intervencional: Atribuição Paralela
- Mascaramento: Dobro
Armas e Intervenções
Grupo de Participantes / Braço |
Intervenção / Tratamento |
|---|---|
|
Experimental: Active tTIs Group
Participants will receive individualized active transcranial temporal interference stimulation targeting the cerebellar dentate nucleus contralateral to the cerebral lesion, 20 minutes per session, once daily for 20 consecutive days, combined with routine rehabilitation therapy. |
Individualized active stimulation will be administered via the NervioX-1000 temporal interference stimulation system. The cerebellar dentate nucleus contralateral to the cerebral lesion is targeted using an electrode montage and current ratio optimized based on each participant's structural magnetic resonance imaging and finite-element electric field modeling. Stimulation parameters are kept constant throughout the intervention. Each session lasts 20 minutes, including 30-second ramp-up and ramp-down periods, with treatment administered once daily for 20 consecutive days. |
|
Comparador Falso: Sham tTIs Group
Participants will receive sham transcranial temporal interference stimulation followed by the same standardized routine rehabilitation therapy. The sham procedure will use the same device, electrode montage, session duration, and ramp sensations as active stimulation but will not deliver sustained active stimulation. |
Sham stimulation will be delivered using the same device, individualized electrode montage, positioning procedures, and session schedule as active stimulation. The device will reproduce the initial ramp-up and brief stimulation sensations and will then ramp down without delivering sustained active stimulation. A brief terminal ramp will reproduce end-of-session sensations. Each sham session lasts 20 minutes, including 30-second ramp-up and ramp-down periods, administered once daily for 20 consecutive days. |
O que o estudo está medindo?
Medidas de resultados primários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Fugl-Meyer Assessment of Upper Extremity (FMA-UE)
Prazo: 20 days after the start of intervention
|
Change in Fugl-Meyer Assessment of Upper Extremity score, range 0-66; higher score indicates better upper limb motor function. |
20 days after the start of intervention
|
Medidas de resultados secundários
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
Action Research Arm Test (ARAT)
Prazo: 20 days after the start of intervention
|
The Action Research Arm Test scale is used to assess upper limb activity and functional ability. Total possible scores range from 0 to 57. Higher scores indicate better upper limb functional performance. |
20 days after the start of intervention
|
|
Global disability: Modified Rankin Scale (mRS)
Prazo: 20 days after the start of intervention
|
The Modified Rankin Scale is an ordinal scale used to assess functional disability and dependence in activities of daily living after stroke. Scores range from 0 to 6. Higher scores indicate worse functional outcome, with a score of 6 representing death. |
20 days after the start of intervention
|
|
National Institutes of Health Stroke Scale (NIHSS)
Prazo: 20 days after the start of intervention
|
The National Institutes of Health Stroke Scale is used to quantify neurological deficit after stroke. Total possible scores range from 0 to 42. Higher scores indicate more severe neurological impairment (worse outcome). |
20 days after the start of intervention
|
|
Multimodal magnetic resonance imaging (MRI)
Prazo: Assessments were performed at 1 and 20 days after the initiation of the intervention
|
Multimodal MRI, including functional MRI (fMRI), diffusion tensor imaging (DTI), and three-dimensional T1-weighted imaging, is acquired to assess structural-functional coupling of the dentato-thalamo-cortical (DTC) pathway. Structural-functional connectivity (SFC) is calculated as the coupling index between DTI-derived structural connectivity and resting-state fMRI functional connectivity along the DTC pathway. Higher SFC values indicate stronger structural-functional coupling of this pathway. |
Assessments were performed at 1 and 20 days after the initiation of the intervention
|
|
Electroencephalography (EEG)
Prazo: Assessments were performed at 1 and 20 days after the initiation of the intervention
|
EEG is recorded synchronously during temporal interference (TI) stimulation. Inter-trial phase coherence (ITPC) is computed to quantify the consistency of phase-locked cortical responses across trials, ranging from 0 to 1. Higher ITPC indicates more reliable phase-locked cortical activation. |
Assessments were performed at 1 and 20 days after the initiation of the intervention
|
|
Transcranial Magnetic Stimulation (TMS)-Induced Motor Evoked Potentials (MEP)
Prazo: Assessments were performed at 1 and 20 days after the initiation of the intervention
|
Single-pulse transcranial magnetic stimulation (TMS) is delivered over the primary motor cortex. Surface electromyography records motor evoked potentials from the target muscle. Peak-to-peak MEP amplitude is measured in microvolts (μV). Larger amplitude indicates higher corticospinal excitability. |
Assessments were performed at 1 and 20 days after the initiation of the intervention
|
Outras medidas de resultado
Medida de resultado |
Descrição da medida |
Prazo |
|---|---|---|
|
adverse events
Prazo: 20 days after the start of intervention
|
The incidence and severity of adverse events, including adverse events related to the intervention, assessed throughout the intervention period. |
20 days after the start of intervention
|
Colaboradores e Investigadores
Patrocinador
Publicações e links úteis
Publicações Gerais
- Gopalakrishnan R, Cunningham DA, Hogue O, Schroedel M, Campbell BA, Plow EB, Baker KB, Machado AG. Cortico-Cerebellar Connectivity Underlying Motor Control in Chronic Poststroke Individuals. J Neurosci. 2022 Jun 29;42(26):5186-5197. doi: 10.1523/JNEUROSCI.2443-21.2022.
- Wathen CA, Frizon LA, Maiti TK, Baker KB, Machado AG. Deep brain stimulation of the cerebellum for poststroke motor rehabilitation: from laboratory to clinical trial. Neurosurg Focus. 2018 Aug;45(2):E13. doi: 10.3171/2018.5.FOCUS18164.
- Machado A, Baker KB. Upside down crossed cerebellar diaschisis: proposing chronic stimulation of the dentatothalamocortical pathway for post-stroke motor recovery. Front Integr Neurosci. 2012 May 21;6:20. doi: 10.3389/fnint.2012.00020. eCollection 2012.
- Baker KB, Plow EB, Nagel S, Rosenfeldt AB, Gopalakrishnan R, Clark C, Wyant A, Schroedel M, Ozinga J 4th, Davidson S, Hogue O, Floden D, Chen J, Ford PJ, Sankary L, Huang X, Cunningham DA, DiFilippo FP, Hu B, Jones SE, Bethoux F, Wolf SL, Chae J, Machado AG. Cerebellar deep brain stimulation for chronic post-stroke motor rehabilitation: a phase I trial. Nat Med. 2023 Sep;29(9):2366-2374. doi: 10.1038/s41591-023-02507-0. Epub 2023 Aug 14.
- He L, Wei Y, Gao C, Qiu S, Liu T, Gao Q. Magnetic Resonance Imaging-Guided Temporal Interference Stimulation of the Cerebellar Fastigial Nucleus in Stroke Patients for Balance. J Vis Exp. 2026 May 15;(231). doi: 10.3791/70982.
- Bonni S, Motta C, Pellicciari MC, Casula EP, Cinnera AM, Maiella M, Picazio S, Tramontano M, Sallustio F, Koch G. Intermittent Cerebellar Theta Burst Stimulation Improves Visuo-motor Learning in Stroke Patients: a Pilot Study. Cerebellum. 2020 Oct;19(5):739-743. doi: 10.1007/s12311-020-01146-2.
- Liao LY, Zhu Y, Peng QY, Gao Q, Liu L, Wang QH, Gao SH, Tao Y, Huang H, Xu PD, Gao CY. Intermittent Theta-Burst Stimulation for Stroke: Primary Motor Cortex Versus Cerebellar Stimulation: A Randomized Sham-Controlled Trial. Stroke. 2024 Jan;55(1):156-165. doi: 10.1161/STROKEAHA.123.044892. Epub 2023 Nov 30.
- Li X, Baker KB, O'Laughlin K, Chen J, Hogue O, Machado AG, Plow EB. Paired DBS and TMS Reveals Dentato-Cortical Facilitation Underlying Upper Extremity Movement in Chronic Stroke Survivors. Neurorehabil Neural Repair. 2024 Feb;38(2):109-121. doi: 10.1177/15459683231219265. Epub 2023 Dec 29.
- Machado AG, Baker KB, Schuster D, Butler RS, Rezai A. Chronic electrical stimulation of the contralesional lateral cerebellar nucleus enhances recovery of motor function after cerebral ischemia in rats. Brain Res. 2009 Jul 14;1280:107-16. doi: 10.1016/j.brainres.2009.05.007. Epub 2009 May 12.
Datas de registro do estudo
Datas Principais do Estudo
Início do estudo (Estimado)
Conclusão Primária (Estimado)
Conclusão do estudo (Estimado)
Datas de inscrição no estudo
Enviado pela primeira vez
Enviado pela primeira vez que atendeu aos critérios de CQ
Primeira postagem (Real)
Atualizações de registro de estudo
Última Atualização Postada (Real)
Última atualização enviada que atendeu aos critérios de controle de qualidade
Última verificação
Mais Informações
Termos relacionados a este estudo
Palavras-chave
Termos MeSH relevantes adicionais
Outros números de identificação do estudo
- TIMES
Plano para dados de participantes individuais (IPD)
Planeja compartilhar dados de participantes individuais (IPD)?
Descrição do plano IPD
Individual participant data (IPD) will not be shared. The data involves sensitive personal health information of participants, and there is no plan to release the individual-level raw data to other researchers due to privacy and data security considerations.
Informações sobre medicamentos e dispositivos, documentos de estudo
Estuda um medicamento regulamentado pela FDA dos EUA
Estuda um produto de dispositivo regulamentado pela FDA dos EUA
Essas informações foram obtidas diretamente do site clinicaltrials.gov sem nenhuma alteração. Se você tiver alguma solicitação para alterar, remover ou atualizar os detalhes do seu estudo, entre em contato com register@clinicaltrials.gov. Assim que uma alteração for implementada em clinicaltrials.gov, ela também será atualizada automaticamente em nosso site .