High-definition Transcranial Electrical Stimulation for Upper Extremity Rehabilitation

NCT06409143 | Recruiting

• 1 other identifier: 202309053DINB
• Study Type: interventional
• Target: 152
• Locations: 1 country
• Sites: 3

Brief Summary

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.

Conditions

Stroke

Keywords

Stroke; High-Definition Transcranial Electrical Stimulation; Upper-limb rehabilitation; Transcranial electrical stimulation; Neuroplasticity

Outcome Measures

Primary Outcomes (2)

• Pre- and 3-month change in motor function of the upper limbs assessed by Fugl-Meyer Assessment of Upper Extremity (FMA-UE)

  The FMA-UE assesses motor functioning of upper extremity. Each movement is estimated by a 3-point scale (0-1-2). The total score of the FMA-UE is 66, and a higher score indicates that the patient has better movement ability.

  Baseline (within 7 days ahead to the 1st intervention session), after 3-week intervention (within 7 days after the last intervention session), follow up (3-month after post-test)

• Pre- and 3-month change in motor function of the upper limbs assessed by Action Research Arm Test (ARAT)

  ARAT consists of 19 items,including grasp (6 items), grip (6 items), pinch (6 items), and gross movement (3 items). Each item is scored on a scale of 0-1-2-3, where 0 indicates the complete inability to perform the movement, 1 indicates partial completion of the movement, 2 indicates independent completion of the movement but with excessive time or difficulty, and 3 indicates a movement pattern that is roughly normal. The total score ranges from 0 to 57, with higher scores indicating better upper limb functional ability.

  Baseline (within 7 days ahead to the 1st intervention session), after 3-week intervention (within 7 days after the last intervention session), follow up (3-month after post-test)

Secondary Outcomes (5)

• Pre- and 3-month change in motor function of the upper limbs assessed by Modified Ashworth Scale (MAS)

  Baseline (within 7 days ahead to the 1st intervention session), after 3-week intervention (within 7 days after the last intervention session), follow up (3-month after post-test)

• Pre- and 3-month change in sensory function of the upper limbs assessed by Rivermead Assessment of Somatosensory Performance (RASP)

  Baseline (within 7 days ahead to the 1st intervention session), after 3-week intervention (within 7 days after the last intervention session), follow up (3-month after post-test)

• Pre- and 3-month change in used and quality of affected extremity assessed by Motor Activity Log (MAL)

  Baseline (within 7 days ahead to the 1st intervention session), after 3-week intervention (within 7 days after the last intervention session), follow up (3-month after post-test)

• Pre- and 3-month change in quality of life assessed by Stroke Impact Scale 3.0 (ML-SIS)

  Baseline (within 7 days ahead to the 1st intervention session), after 3-week intervention (within 7 days after the last intervention session), follow up (3-month after post-test)

• Everytime report for the incidence of treatment-emergent adverse events [safety and tolerability]

  Within 10 minutes after each intervention session (a total of 15 sessions, 5 sessions/week, lasting 3 weeks)

Other Outcomes (2)

• Pre- and 3-month change in cerebral hemodynamic assessed by functional near-infrared spectroscopy (fNIRS)

  During each intervention session (a total of 15 sessions, 5 sessions/week, lasting 3 weeks)

• Pre- and 3-month change in neuronal activation assessed by motor evoked potential, MEP

  Baseline (within 7 days ahead to the 1st intervention session), after 3-week intervention (within 7 days after the last intervention session), follow up (3-month after post-test)

Study Arms (4)

Excitatory stimulation on the affected hemisphere & UE rehabilitation

EXPERIMENTAL

10 minutes sham inhibitory HD-tES over the unaffected hemisphere's M1 followed by 10 minutes of excitatory HD-tES over the affected hemisphere's M1, combined with upper extremity rehabilitation of affected side.

Device: HD-tES; Other: UE rehabilitation

Inhibitory stimulation on the unaffected hemisphere & UE rehabilitation

EXPERIMENTAL

10-minute active inhibitory HD-tES over the unaffected hemisphere's M1 followed by 10 minutes of sham excitatory HD-tES over the affected hemisphere's M1, combined with upper extremity rehabilitation of affected side.

Device: HD-tES; Other: UE rehabilitation

Simultaneous bilateral stimulation & UE rehabilitation

EXPERIMENTAL

Combined with upper extremity rehabilitation of affected side.

Device: HD-tES; Device: HD-tES (Bilateral)

Sham stimulation& UE rehabilitation

SHAM COMPARATOR

The sham control group will receive sham HD-tCES combined with upper extremity rehabilitation of affected side.

Device: Sham HD-tES; Other: UE rehabilitation

Interventions

HD-tES DEVICE

The intensity of HD-tES is set at 2 mA, the current intensity ramps up to 2 mA within 5 seconds, remains at 2 mA for 10 minutes, and then ramps down to zero within 5 seconds. For the sham stimulation, the current intensity ramps up and down at the first and last 10 seconds, with the remaining 10 minutes set at 0 mA. The inhibitory and excitatory waveform will be selected based on results of sub-project 1.

Excitatory stimulation on the affected hemisphere & UE rehabilitation; Inhibitory stimulation on the unaffected hemisphere & UE rehabilitation; Simultaneous bilateral stimulation & UE rehabilitation

Sham HD-tES DEVICE

The intensity of HD-tES is set at 2 mA, the current intensity ramps up to 2 mA within 5 seconds, remains at 2 mA for 10 minutes, and then ramps down to zero within 5 seconds. For the sham stimulation, the current intensity ramps up and down at the first and last 10 seconds, with the remaining 10 minutes set at 0 mA. The inhibitory and excitatory waveform will be selected based on results of sub-project 1.

Sham stimulation& UE rehabilitation

UE rehabilitation OTHER

Upper extremity rehabilitation programs will be selected and graded in accordance with each patient's upper extremity function and specific aims of activities of daily living. Upper extremity rehabilitation will be provided for 60 minutes each time, 5 times a week, lasting for 3 weeks.

Excitatory stimulation on the affected hemisphere & UE rehabilitation; Inhibitory stimulation on the unaffected hemisphere & UE rehabilitation; Sham stimulation& UE rehabilitation

HD-tES (Bilateral) DEVICE

The intensity of HD-tES is set at 2 mA, the current intensity ramps up to 2 mA within 5 seconds, remains at 2 mA for 10 minutes, and then ramps down to zero within 5 seconds.

Simultaneous bilateral stimulation & UE rehabilitation

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• \- 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).

You may not qualify if:

• \- Sub-Project 1 (Healthy)
• 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.
• Participation in other invasive or non-invasive brain stimulation research studies.
• 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 alcohol or substance abuse.
• Damaged skin at the stimulation site, electrode contact, or device wearing site.
• 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).

Sponsors & Collaborators

• National Taiwan University Hospital: lead

Study Sites (3)

New Taipei City Tucheng Hospital

New Taipei City, Taiwan

NOT YET RECRUITING

National Taiwan University Hospital

Taipei, Taiwan

RECRUITING

Taipei Medical University Hospital

Taipei, Taiwan

RECRUITING

MeSH Terms

Conditions

Stroke

Condition Hierarchy (Ancestors)

Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Central Study Contacts

Mon-Ting Lin

CONTACT

+886-972-652-480; B96401093@ntu.edu.tw

Yi-Jing Huang

CONTACT

+886-911-164-386; yijinghuang@ntu.edu.tw

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 7, 2024
• First Posted: May 10, 2024
• Study Start: August 15, 2024
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): November 30, 2026
• Last Updated: August 16, 2024

Record last verified: 2024-05

Locations

TW (3)