NCT06409143

High-definition Transcranial Electrical Stimulation for Upper Extremity Rehabilitation

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

• Status: Recruiting
• Phase: N/A
• Study type: Interventional
• Enrollment: 152 (estimated)
• Sponsor: National Taiwan University Hospital · Academic / Other
• Sex: All
• Age: 18 Years
• Healthy volunteers: Accepted

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.

Detailed description

This project comprises two sub-projects: 1. Investigation of Neuromodulatory Effects of Stimulation Waveforms and Optimal Stimulation Waveform for Patients with Stroke : a crossover trial will compare the effects of seven high-definition transcranial electrical stimulation (HD-tES) waveforms on neural excitatory or inhibitory activity in healthy adults. These waveforms include three excitatory wave forms (anodal direct current (aDC), intermittent theta burst stimulation (iTBS), and a combination of aDC and iTBS (aDC+iTBS)) and three inhibitory wave forms (cathodal direct current (cDC), continuous theta burst stimulation (cTBS), and a combination of cDC and cTBS (cDC+cTBS)), along with a sham stimulation condition. Changes in cortical excitability over a 2-hour period before and after stimulation will be tracked. Validation of the optimal stimulation waveform for patients with stroke will be conducted through a crossover trial comparing three excitatory HD-tES waveforms for enhancing affected brain activity and three inhibitory HD-tES waveforms for reducing activity in the unaffected hemisphere. Changes in cortical excitability over a 2-hour period before and after stimulation will be monitored. 2. Exploration of the Effects of Unilateral and Bilateral HD-tES in Patients with Subacute Stroke: A triple-blind randomized controlled trial will be conducted to compare four neuromodulatory modes combined with conventional upper limb rehabilitation on brain activity and upper limb function in patients with subacute stroke. These modes include excitatory stimulation on the affected hemisphere (based on results from sub-project one, choosing from aDC, iTBS, or aDC+iTBS), inhibitory stimulation on the unaffected hemisphere (based on results from sub-project one, choosing from cDC, cTBS, or cDC+cTBS), simultaneous bilateral stimulation, and sham stimulation. The primary outcome will focus on upper limb functional activity and upper limb motor function, with other indicators serving as secondary outcomes.

Conditions

• Stroke

Interventions

Type	Name	Description
DEVICE	HD-tES	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.
DEVICE	Sham HD-tES	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.
OTHER	UE rehabilitation	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.
DEVICE	HD-tES (Bilateral)	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.

Timeline

• Start date: 2024-08-15
• Primary completion: 2026-08-31
• Completion: 2026-11-30
• First posted: 2024-05-10
• Last updated: 2024-08-16

Locations

3 sites across 1 country: Taiwan