High-definition Transcranial Electrical Stimulation for Lower Limb Stroke Rehabilitation

Effects of High-definition Transcranial Electrical Stimulation on the Lower Extremity in Patients With Stroke

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. The tCES has been applied in clinical trials related to rehabilitation research in recent years, and the safety and effectiveness have also been established. However, the existing tCES products effect on the whole brain networks and lack special waveforms. We developed a wearable high-definition tCES (HD-tCES) with special waveforms. This novel stimulation system will result in more precise and focal stimulation of selected brain regions with special waveforms to display better neuromodulation performance. In this study, we will preliminarily examine the effects and safety of the HD-tCES on lower extremity in patients with stroke. We expect that the HD-tCES combined with the lower extremity rehabilitation can shorten the duration of rehabilitative periods, improve stroke patients' activity of daily living, reduce the care burden of patients' family, and subsequently decrease the cost of health care insurance.

Study Overview

• Status: Recruiting
• Conditions: Stroke
• Intervention / Treatment: Device: HD-tCES; Other: Lower limb rehabilitation; Device: Sham HD-tCES

• Study Type: Interventional
• Enrollment (Anticipated): 48
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Chien-Hung Lai, PhD; Phone Number: 1236 +886-2-27372181; Email: chlai@tmu.edu.tw

Study Locations

• Taiwan
  • New Taipei City, Taiwan, 235
    • Recruiting
    • Taipei Medical University-Shuang Ho Hospital,Ministry of Health and Welfare
    • Contact: Hung-Chou Chen, MD; Phone Number: +886-970-747-158; Email: b8601084@tmu.edu.tw
    • Sub-Investigator: Hung-Chou Chen, MD
    • Sub-Investigator: Shih-Wei Huang, PhD
  • Taipei, Taiwan, 110
    • Recruiting
    • Taipei Medical University Hospital
    • Contact: Chien-Hung Lai, PhD; Phone Number: 1236 +886-2-27372181; Email: chlai@tmu.edu.tw
    • Principal Investigator: Chien-Hung Lai, PhD
  • Taipei, Taiwan, 116
    • Recruiting
    • Taipei Municipal Wanfang Hospital - Taipei Medical University
    • Contact: Kwang-Hwa Chang, MS; Phone Number: +886-970-746-881; Email: chang2773@gmail.com
    • Sub-Investigator: Kwang-Hwa Chang, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. With a diagnosis of stroke.
2. Age ≥ 20 years.
3. Hemiplegia, Brunnstrom stage III-V.
4. 6 months to 5 years after stroke.
5. Muscular inelasticity (spasticity) 1-3 on the affected lower limb, evaluated by the Modified Ashworth Scale.
6. Ability to walk for 10 min non-stop with no gait aids or ability to walk 20 m with supervision or slight assistance.

Exclusion Criteria:

1. Intolerance to electrical stimulation.
2. Contracture on lower extremities, and limitation in joint range of motion.
3. Severe spasticity.
4. Ossification or inflammation in muscle tissue.
5. A history of arrhythmia.
6. Implantable medical electronic devices (e.g., like pacemaker).
7. Metal implants in the head or neck.
8. Wounds on the skin of head.
9. A history of brain surgery or severe brain trauma.
10. Severe cognitive or psychiatric disorders (e.g., schizophrenia, depression or bipolar disorder).
11. A history of seizure or other brain pathology.
12. Drug or alcohol abuse.
13. Malignant neoplasm or rheumatism disorder (e.g., SLE, RA, AS, IBD)
14. Undergoing other non-invasive brain stimulation.
15. Intra-cerebral lesions (such as brain tumors, arteriovenous tumors).
16. History of encephalitis or meningitis.
17. Stroke lesion in cerebellum or brainstem.
18. Leg amputation.
19. Sleep deprivation.
20. Severe or recent heart disease.
21. Subjects who use drugs that may lower the seizure threshold.
22. Pregnant or breastfeeding women.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: HD-tCES & lower limb rehabilitation; The experiment group will receive HD-tCES combined with lower limb rehabilitation of affected side.	Device: HD-tCES; The high definition transcranial electrical stimulation was applied using a 1*4 ring electrode configuration. The anodal electrode was placed on the ipsilesional C1/C2, and the remaining 4 cathodal electrodes were placed in a radius of approximately 7.5 cm from anode (Cz, F3, T7, and P3 on the left hemisphere or Cz, F4, T8, and P4 on the right hemisphere). HD-tCES will be applied for 20 minutes at an intensity of 1.0 mA direct current stimulation and a specific-added waveform each time, 3 times a week, lasting for 4 weeks.; Other: Lower limb rehabilitation; Lower limb rehabilitation programs will be selected and graded in accordance with each patient's lower limb function and specific aims of activities of daily living. Lower limb rehabilitation will be provided for 30 minutes each time, 3 times a week, lasting for 4 weeks.
SHAM_COMPARATOR: Sham HD-tCES & lower limb rehabilitation; The sham control group will receive sham HD-tCES combined with lower limb rehabilitation of affected side.	Other: Lower limb rehabilitation; Lower limb rehabilitation programs will be selected and graded in accordance with each patient's lower limb function and specific aims of activities of daily living. Lower limb rehabilitation will be provided for 30 minutes each time, 3 times a week, lasting for 4 weeks.; Device: Sham HD-tCES; The high definition transcranial electrical stimulation was applied using a 1*4 ring electrode configuration. The anodal electrode was placed on the ipsilesional C1/C2, and the remaining 4 cathodal electrodes were placed in a radius of approximately 7.5 cm from anode (Cz, F3, T7, and P3 on the left hemisphere or Cz, F4, T8, and P4 on the right hemisphere). Sham HD-tCES will consist of a 5-second ramp up to 1.0 mA direct current stimulation and a specific-added waveform followed immediately by a 5-second ramp down, no current in the middle 19 minutes 40 seconds, and a ramp-up and ramp-down period during the last 10 seconds.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the Fugl-Meyer Assessment lower extremity scale (FMA-LE) after intervention	The FMA-LE assesses motor functioning of lower extremity. Each movement is estimated by a 3-point scale (0-1-2). The total score of the FMA-LE is 34, and a higher score indicates that the patient has better movement ability.	Baseline (within 7 days ahead to the 1st intervention session) and after 4-week intervention (within 7 days after the last intervention session)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change from baseline in the Berg Balance Scale (BBS) after intervention	The BBS is used to objectively determine a patient's ability to safely balance during a series of predetermined tasks. It contains 14 items with each item consisting of a five-point ordinal scale ranging from 0 to 4. A higher score indicates that the patient has better balance.	Baseline (within 7 days ahead to the 1st intervention session) and after 4-week intervention (within 7 days after the last intervention session)
Change from baseline in the Timed Up and Go Test (TUG) after intervention	The TUG assesses a patient's mobility and requires both static and dynamic balance. It measures the time that a person takes to rise from a chair, walk three meters, turn around, walk back to the chair, and sit down.	Baseline (within 7 days ahead to the 1st intervention session) and after 4-week intervention (within 7 days after the last intervention session)
Change from baseline in the Gait Evaluation after intervention	The Gait Evaluation includes cadence, stride duration, stride length, and velocity.	Baseline (within 7 days ahead to the 1st intervention session) and after 4-week intervention (within 7 days after the last intervention session)
Change from baseline in the Modified Ashworth Scale (MAS) after intervention	The MAS is commonly used in clinical practice for grading spasticity. The MAS is rated on a 6-point scale (0, 1, 1+, 2, 3, 4), and a higher score indicates that the patient has higher muscle tension. The muscles being assessed include hip flexor, hip extensor, knee flexor, knee extensor, ankle dorsiflexor, and ankle plantarflexor.	Baseline (within 7 days ahead to the 1st intervention session) and after 4-week intervention (within 7 days after the last intervention session)
Change from baseline motor evoked potential (MEP) after intervention	The MEP elicited in peripheral muscles by transcranial magnetic stimulation over motor cortex is one of the hallmark measures for non-invasive quantification of cortical excitability.	Baseline (within 7 days ahead to the 1st intervention session) and after 4-week intervention (within 7 days after the last intervention session)
Incidence of treatment-emergent adverse events	Immediately after each HD-tCES stimulation, the patient will be questioned about eventual side effect.	Within 10 minutes after each intervention session (a total of 12 sessions, 3 sessions/week, lasting 4 weeks)

Collaborators and Investigators

• Sponsor: Taipei Medical University Hospital

Study record dates

Study Major Dates

• Study Start (ACTUAL): August 20, 2020
• Primary Completion (ANTICIPATED): October 31, 2023
• Study Completion (ANTICIPATED): December 31, 2023

Study Registration Dates

• First Submitted: August 13, 2020
• First Submitted That Met QC Criteria: August 13, 2020
• First Posted (ACTUAL): August 17, 2020

Study Record Updates

• Last Update Posted (ACTUAL): January 31, 2023
• Last Update Submitted That Met QC Criteria: January 28, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Keywords: Stroke, Transcranial electrical stimulation, Lower-limb rehabilitation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: N202004091

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No