Novel Brain Neurotechnology for Optimizing Precision Mirror Therapy in Stroke

NCT ID: NCT05238272

Last Updated: 2022-02-14

Basic Information

• Recruitment Status: RECRUITING
• Clinical Phase: NA
• Total Enrollment: 128 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-03-01
• Study Completion Date: 2026-12-31

Brief Summary

The primary aim of this project will be to determine the effects of the tRNS-augmented unilateral and bilateral MT, and their effects relative to the control interventions (sham tRNS with unilateral or bilateral MT) on restoring health outcomes including motor function, daily function, quality of life and self-efficacy, and motor control strategy as well as brain activities (electroencephalography, EEG) in stroke patients.

Detailed Description

Developing effective rehabilitation interventions to maximize functional recovery remains to be a major challenge for stroke rehabilitation. Transcranial random noise stimulation (tRNS) has emerged as a promising brain neurotechnology to enhance neural plasticity to augment treatment effects of stroke neuorehabilitation therapies. Compared to traditional brain neurotechnology such as transcranial direct current stimulation (tDCS), tRNS does not have polarity constraints, thus providing more consistent modulatory effects, less response variability and less adverse effects, which make it a potentially ideal approach to combine with stroke rehabilitation therapies. Mirror therapy (MT) is effective at improving sensorimotor recovery in stroke patients. Because of its easiness for use in clinical settings, MT has been recommended by American Heart Association as a promising intervention for stroke patients. Combining tRNS with MT could be an appealing approach to further boost brain plasticity to maximize MT treatment benefits in the clinical settings. However, MT can be delivered using unilateral or bilateral approaches, which may induce differential treatment benefits. Identifying the optimal combination of MT with tRNS on recovering functions and brain mechanisms will be imperative for development of evidence-based precision brain neurotechnology-augmented stroke rehabilitation.

Therefore, this research project will (1) compare the effects of the tRNS-augmented unilateral and bilateral MT, and their effects relative to the control interventions (sham tRNS with unilateral or bilateral MT) comprehensively on motor function, daily function, quality of life and self-efficacy, motor control strategy and brain activities (electroencephalography, EEG) in stroke patients; (2) examine the retention effects and possible delayed response of tRNS-augmented unilateral and bilateral MT at 3-month and 6-month follow-up and (3) identify the predictors of the treatment success to determine good responders to the tRNS-augmented unilateral and bilateral MT to facilitate clinical translation of the intervention.

The investigator will conduct a randomized, sham controlled clinical trial with 128 stroke patients in this 5-year project. Patients will be randomly assigned to (1) tRNS-augmented unilateral MT, (2) tRNS-augmented bilateral MT, (3) sham tRNS with unilateral MT, and (4) sham tRNS with bilateral MT. Participants will receive 20 intervention sessions (90 minutes/day, 5 days/week, for 4 consecutive weeks). The outcome measures will include behavioral assessments to evaluate motor and daily function, quality of life and self-efficacy; kinematic assessments to evaluate motor control strategy; and EEG to assess brain activities (power). The behavioral measures will be performed at pre-test, interim-test, post-test, and 3-month and 6-month follow-up. The kinematic and EEG assessment will be administered at pre-test and post-test. In addition, the EEG assessment will be conducted during the intervention period to evaluate the dynamical changes of brain activities.

This research project will provide scientific evidence of the treatment effects of brain neurotechnology-augmented stroke rehabilitation therapy. Specifically, the findings will elucidate behavioral changes and possible biomechanical and brain mechanisms associated with the novel tRNS-augmented MT. In addition, the results will reveal the characteristics of good responders to the combined intervention. The overall results will contribute to formulation of precision hybrid brain neurotechnology with stroke rehabilitation therapies to maximize neural and functional recovery after stroke.

Conditions

Cerebrovascular Accident

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: DOUBLE

Study Groups

tRNS-augmented unilateral MT

A battery driven multi-channel electrical stimulator will deliver alternating electrical current over the scalp through sailine-soaked sponge electrodes (surface area = 25 cm2). The stimulation electrodes were directly positioned on an adult sized cap that will be worn by the participants, and labeled according to the 10-20 EEG system of electrode positioning. The stimulation intensity will be ramp up to 1.5 to 2 mA.

For the unilateral MT, the participants will practice movements using only the unaffected arm while the affected arm will remain relaxed behind the mirror during MT training. The training therapists will instruct the participants to look at the mirror reflection of the unaffected arm and imagine that it is the affected arm performing the task.

Group Type: EXPERIMENTAL

Transcranial random noise stimulation (tRNS)

Intervention Type: DEVICE

There will be 20 minutes of stimulation (real tRNS or sham tRNS), 40 minutes of MT (unilateral or bilateral) and 30 minutes of functional task training.

the unilateral MT

Intervention Type: BEHAVIORAL

For the unilateral MT, the participants will practice movements using only the unaffected arm while the affected arm will remain relaxed behind the mirror during MT training. The training therapists will instruct the participants to look at the mirror reflection of the unaffected arm and imagine that it is the affected arm performing the task.

tRNS-augmented bilateral MT

A battery driven multi-channel electrical stimulator will deliver alternating electrical current over the scalp through sailine-soaked sponge electrodes (surface area = 25 cm2). The stimulation electrodes were directly positioned on an adult sized cap that will be worn by the participants, and labeled according to the 10-20 EEG system of electrode positioning. The stimulation intensity will be ramp up to 1.5 to 2 mA.

For the bilateral MT, the participants will be encouraged to move the affected arm as symmetrically and simultaneously as the unaffected hand during MT training. At the same time, participants will also be instructed to look at the mirror reflection of the unaffected arm and imagine that it is the affected arm performing the task.

Group Type: EXPERIMENTAL

Transcranial random noise stimulation (tRNS)

Intervention Type: DEVICE

There will be 20 minutes of stimulation (real tRNS or sham tRNS), 40 minutes of MT (unilateral or bilateral) and 30 minutes of functional task training.

the bilateral MT

Intervention Type: BEHAVIORAL

For the bilateral MT, the participants will be encouraged to move the affected arm as symmetrically and simultaneously as the unaffected hand during MT training. At the same time, participants will also be instructed to look at the mirror reflection of the unaffected arm and imagine that it is the affected arm performing the task. The activities practiced during MT will include intransitive movements (e.g., flexion and extension of the wrist) and transitive movements (e.g., picking up a pen).

sham tRNS with unilateral MT

For the sham tRNS condition, the electrode placement will be the same as the real stimulation conditions. The current will first turn up for 30 seconds and subsequently turn off in the next 30 seconds .

For the unilateral MT, the participants will practice movements using only the unaffected arm while the affected arm will remain relaxed behind the mirror during MT training. The training therapists will instruct the participants to look at the mirror reflection of the unaffected arm and imagine that it is the affected arm performing the task.

Group Type: SHAM_COMPARATOR

sham tRNS

Intervention Type: DEVICE

the electrode placement will be the same as the real stimulation conditions. The current will first turn up for 30 seconds and subsequently turn off in the next 30 seconds

the unilateral MT

Intervention Type: BEHAVIORAL

For the unilateral MT, the participants will practice movements using only the unaffected arm while the affected arm will remain relaxed behind the mirror during MT training. The training therapists will instruct the participants to look at the mirror reflection of the unaffected arm and imagine that it is the affected arm performing the task.

sham tRNS with bilateral MT

For the sham tRNS condition, the electrode placement will be the same as the real stimulation conditions. The current will first turn up for 30 seconds and subsequently turn off in the next 30 seconds .

For the bilateral MT, the participants will be encouraged to move the affected arm as symmetrically and simultaneously as the unaffected hand during MT training. At the same time, participants will also be instructed to look at the mirror reflection of the unaffected arm and imagine that it is the affected arm performing the task.

Group Type: SHAM_COMPARATOR

sham tRNS

Intervention Type: DEVICE

the electrode placement will be the same as the real stimulation conditions. The current will first turn up for 30 seconds and subsequently turn off in the next 30 seconds

the bilateral MT

Intervention Type: BEHAVIORAL

For the bilateral MT, the participants will be encouraged to move the affected arm as symmetrically and simultaneously as the unaffected hand during MT training. At the same time, participants will also be instructed to look at the mirror reflection of the unaffected arm and imagine that it is the affected arm performing the task. The activities practiced during MT will include intransitive movements (e.g., flexion and extension of the wrist) and transitive movements (e.g., picking up a pen).

Interventions

Transcranial random noise stimulation (tRNS)

There will be 20 minutes of stimulation (real tRNS or sham tRNS), 40 minutes of MT (unilateral or bilateral) and 30 minutes of functional task training.

Intervention Type: DEVICE

sham tRNS

the electrode placement will be the same as the real stimulation conditions. The current will first turn up for 30 seconds and subsequently turn off in the next 30 seconds

Intervention Type: DEVICE

the unilateral MT

For the unilateral MT, the participants will practice movements using only the unaffected arm while the affected arm will remain relaxed behind the mirror during MT training. The training therapists will instruct the participants to look at the mirror reflection of the unaffected arm and imagine that it is the affected arm performing the task.

Intervention Type: BEHAVIORAL

the bilateral MT

For the bilateral MT, the participants will be encouraged to move the affected arm as symmetrically and simultaneously as the unaffected hand during MT training. At the same time, participants will also be instructed to look at the mirror reflection of the unaffected arm and imagine that it is the affected arm performing the task. The activities practiced during MT will include intransitive movements (e.g., flexion and extension of the wrist) and transitive movements (e.g., picking up a pen).

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

1. ≥ 3 months onset from a first-ever unilateral stroke;

2. an initial FMA scores between 18 to 56, indicating moderate to mild upper extremity motor impairment (Thielman, Kaminski, & Gentile, 2008);

3. age between 35 to 85;

4. no excessive spasticity in any of the joints of the affected arm (shoulder, elbow, wrist and fingers);

5. ability to follow instructions and perform tasks (Mini Mental State Examination scores ≥24);

6. no participation in any neurorehabilitation experiments or drug clinical trials and

7. willing to provide written informed consent.

Exclusion Criteria

1. contradiction to tRNS including a history of epilepsy, pregnant, having pacemakers and metallic implants in the neck and heads (Rossi, Hallett, Rossini, Pascual-Leone, & Safety of, 2009);

2. History of drug or alcohol abuse(Rossi et al., 2009);

3. concomitant neurological conditions such as dementia, Parkinson's disease, brain tumor, brain injury and other brain diseases (such as intracranial hypertension or cerebral edema);

4. Botulinum toxin injections 3 months before enrollment

5. have unstable cardiovascular status such as uncontrolled hypertension or New York Heart Association (NYHA) Class III/IV heart failure or are not suitable for receiving tRNS by the physician's assessments.

• Minimum Eligible Age: 35 Years
• Maximum Eligible Age: 85 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

Chang Gung Memorial Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Locations

Chang Gung Memotial Hospital

Taoyuan District, , Taiwan

Site Status: RECRUITING

Countries

Taiwan

Central Contacts

Ching-yi Wu, ScD

Role: CONTACT

cywu@mail.cgu.edu.tw

#886-3-2118800 ext. 5761

Facility Contacts

Ching-Yi Wu, ScD

Role: primary

cywu@mail.cgu.edu.tw

+886-3-2118800 ext. 5761

Other Identifiers

202100509A0

Identifier Type: -

Identifier Source: org_study_id