Electrical brain stimulation with upper limb rehabilitation after stroke

Trial details

Who runs it

National Taiwan University Hospital

Trial code

NCT06409143

Record updated

20 August 2026

Original description

Upper limb hemiparesis is the most common sequelae in patients, severely impacting their independence and quality of life. Transcranial electrical stimulation (tCES) is a non-invasive and safe treatment, which uses a low direct current or alternating current to change the excitability of the cerebral cortex. It can induces long-term potentiation-like or long-term depression-like effects, thereby modulating the cortical excitability. In recent years, researchers have developed high-definition (HD) devices, which integrate high definition ring electrode configurations and incorporate direct current with theta burst stimulation waveforms. Diverging from traditional transcranial direct current stimulation (tDCS), which applies weak currents (0.5-2 mA) through two large sponge electrodes (25~35 cm\^2) externally to the scalp for widespread non-specific cortical stimulation, HD-tES employs an array of small-area electrodes (1 cm\^2) to control current distribution over localized cortical regions, thereby enhancing spatial accuracy. However, there is a lack of studies validating the optimal waveform for HD-tES, as well as clinical evidence in subacute stroke populations. The optimal unilateral versus bilateral stimulation modes and their neurological mechanisms for stroke rehabilitation also remain uncertain.Read full original descriptionShow less

Neural Mechanisms and Augmented Efficacy of High-definition Transcranial Electrical Stimulation on Upper-extremity Function in Patients With Subacute Stroke

Upper limb hemiparesis is the most common sequelae in patients, severely impacting their independence and quality of life. Transcranial electrical stimulation (tCES) is a non-invasive and safe treatment, which uses a low direct current or alternating current to change the excitability of the cerebral cortex. It can induces long-term potentiation-like or long-term depression-like effects, thereby modulating the cortical excitability. In recent years, researchers have developed high-definition (HD) devices, which integrate high definition ring electrode configurations and incorporate direct current with theta burst stimulation waveforms. Diverging from traditional transcranial direct current stimulation (tDCS), which applies weak currents (0.5-2 mA) through two large sponge electrodes (25~35 cm\^2) externally to the scalp for widespread non-specific cortical stimulation, HD-tES employs an array of small-area electrodes (1 cm\^2) to control current distribution over localized cortical regions, thereby enhancing spatial accuracy. However, there is a lack of studies validating the optimal waveform for HD-tES, as well as clinical evidence in subacute stroke populations. The optimal unilateral versus bilateral stimulation modes and their neurological mechanisms for stroke rehabilitation also remain uncertain.

Inclusion: Sub-Project 1 (Healthy); Adults aged 18 and above; Confirmed right-handedness using the Edinburgh Handedness Inventory; Sub-Project 1 (Post-stroke patients); Aged 18 and above; Diagnosed with stroke; Post-stroke for more than 6 months; Unilateral hemiparesis; Sub-Project 2 (Subacute-stroke patients); Aged 18 and above; Diagnosed with stroke; Stroke occurred between 7 days to 6 months ago; Unilateral hemiparesis; Degree of recovery for proximal and distal movements of the affected upper limb is Brunnstrom stage III to V; No severe muscle spasticity in any segments of the affected upper limb (Modified Ashworth Scale ≤ 2).

Exclusion: Pregnancy or lactating women. (If female, must be postmenopausal or surgically sterilized. Fertile women must have a negative pregnancy test result. Fertile female patients engaging in heterosexual intercourse, as well as fertile male patients with fertile female partners, must agree to use effective contraception during the trial period and for 4 months after the last dose of the investigational drug, such as oral contraceptives, dual barrier methods, intrauterine devices, or abstain from sexual intercourse during this period; non-fertile women are those who have undergone bilateral oophorectomy or are postmenopausal.); Undergoing other invasive or non-invasive brain stimulation therapies; Pregnancy or lactating women. (If female, must be postmenopausal or surgically sterilized. Fertile women must have a negative pregnancy test result. Fertile female patients engaging in heterosexual intercourse, as well as fertile male patients with fertile female partners, must agree to use effective contraception during the trial period and for 4 months after the last dose of the investigational drug, such as oral contraceptives, dual barrier methods, intrauterine devices, or abstain from sexual intercourse during this period; non-fertile women are those who have undergone bilateral oophorectomy or are postmenopausal.); Undergoing other invasive or non-invasive brain stimulation therapies; Pregnancy or lactating women. (If female, must be postmenopausal or surgically sterilized. Fertile women must have a negative pregnancy test result. Fertile female patients engaging in heterosexual intercourse, as well as fertile male patients with fertile female partners, must agree to use effective contraception during the trial period and for 4 months after the last dose of the investigational drug, such as oral contraceptives, dual barrier methods, intrauterine devices, or abstain from sexual intercourse during this period; non-fertile women are those who have undergone bilateral oophorectomy or are postmenopausal.); History of neurological disorders (e.g., stroke, brain tumor, epilepsy), psychiatric disorders (e.g., substance abuse, major depression, schizophrenia, bipolar disorder), or musculoskeletal disorders of the upper limb; Contraindications to transcranial electrical stimulation, including history of epilepsy, atrial fibrillation, presence of metal implants, cardiac pacemakers, convexity skull defects, or increased intracranial pressure; Skin allergies, contact dermatitis, abnormal pain, hypersensitivity to pain, wounds, or ulcers on the head; History of alcohol or substance abuse; Long-term use of central nervous system affecting medications (such as antidepressants, sedatives) or other medications that may affect seizure threshold; Other conditions deemed unsuitable for transcranial electrical or magnetic stimulation by a physician; Affiliation with any research institution/execution unit (e.g., students from NTU, Taipei Medical University); Sub-Project 1 (Post-stroke patients); Contraindications to transcranial electrical stimulation include a history of epilepsy, atrial fibrillation, presence of metal implants, cardiac pacemakers, convexity skull defects, or increased intracranial pressure; Skin allergies, contact dermatitis, abnormal pain, hypersensitivity to pain, wounds, or ulcers on the head; Severe neurological or psychiatric disorders other than stroke (such as major depression, schizophrenia, substance abuse, organic brain diseases, Parkinson's disease, brain tumors); Use of medications that may lower the seizure threshold; History of alcohol or substance abuse; Long-term use of central nervous system affecting medications (such as antidepressants, sedatives) or other medications that may affect seizure threshold; Other conditions deemed unsuitable for transcranial electrical or magnetic stimulation by a physician; Sub-Project 2 (Subacute-stroke patients); Contraindications to transcranial electrical stimulation include a history of epilepsy, atrial fibrillation, presence of metal implants, cardiac pacemakers, convexity skull defects, or increased intracranial pressure; Skin allergies, contact dermatitis, abnormal pain, hypersensitivity to pain, wounds, or ulcers on the head; Severe neurological or psychiatric disorders other than stroke (such as major depression, schizophrenia, substance abuse, organic brain diseases, Parkinson's disease, brain tumors); Use of medications that may lower the seizure threshold; Severe cognitive impairment or receptive or global aphasia making it difficult to understand instructions; History of alcohol or substance abuse; Long-term use of central nervous system affecting medications (such as antidepressants, sedatives) or other medications that may affect seizure threshold; Other conditions deemed unsuitable for transcranial electrical or magnetic stimulation by a physician; Sub-Project 1 (Healthy); Participation in other invasive or non-invasive brain stimulation research studies; Damaged skin at the stimulation site, electrode contact, or device wearing site; Damaged skin at the stimulation site, electrode contact, or device wearing site; Other muscle and joint problems affecting upper limb function, such as joint contractures, rheumatoid arthritis, myositis ossificans; Hemineglect (including visual, auditory, or sensory neglect); Damaged skin at the stimulation site, electrode contact, or device wearing site.

ClinicalTrials.gov NCT06409143