Neurophysiological and Behavioral Effects of Combining Transcranial Direct Current Stimulation (tDCS) and Modified-Constraint Induced Movement Therapy (mCIMT)

Not Applicable

Recruiting

• Conditions: Stroke; Hemiparesis of the Upper Limb Following Stroke; Stroke Rehabilitatiom

• Registration Number: NCT06786000
• Lead Sponsor: King Saud University

Brief Summary

This clinical trial aims to evaluate the effect of different types of tDCS modulation with mCIMT in improving affected upper-limb motor function for stroke patients. The main question it seeks to answer:

Which type of tDCS (bi-hemispheric, anodal, or cathodal) combined with the mCIMT program leads to greater improvement in affected upper-limb function in patients with stroke? Researchers will compare these three types of tDCS to a sham tDCS. To see which kind of tDCS protocol combined with the mCIMT program will be more effective in improving affected upper-limb function for stroke patients.

Participants will:

1. Participants will receive 12 sessions of mCIMT combined with tDCS or mCIMT alone.

2. Visit the clinic three times a week for four weeks.

3. Participants will do fMRI and TMS before and after the program and three times of assessment before and after two weeks after the program.

Detailed Description

Background: After a stroke, intense motor rehabilitation is required to facilitate motor recovery. In specific, combining tDCS with neurorehabilitation interventions boosts the responses of the brain to the interventions and maximizes the effects of rehabilitation to improve upper limb recovery post-stroke. Objectives: To evaluate the effect of different modes of tDCS modulation with mCIMT in improving affected upper-limb motor recovery for patients with stroke. Method: a randomizing control trial design, after performing a baseline assessment, the participants will be randomly assigned to one of the four groups: the anodal tDCS +mCIMT group, the cathodal tDCS +mCIMT group, the bihemispheric tDCS +mCIMT group, and the mCIMT alone group. Inclusion Criteria, adult participants clinically diagnosed and confirmed by imaging of ischemic or hemorrhagic cerebrovascular accident, participant's age older than 18 years, Stroke onset more than 3 months with unilateral motor deficits, Adequate cognitive function is required to follow instructions. The Arabic version of the Mini-Mental State Examination (MMSE) should be ≥24, 10° of active extension to the metacarpophalangeal and interphalangeal joints and 20° at the wrist, and not participating in other clinical, or research studies at the same time. Exclusion Criteria, Severe muscle spasticity at the affected limb at all joints (the Modified Ashworth Scale scores \> 3), Contraindications to NIBS, unilateral neglect, Other neurologic or orthopedic conditions that may affect hand function, and unstable medical conditions. The total intervention period will be performed 3 times a week for 4 weeks. Each participant will undergo motor impairment and physiological assessments at baseline, during and after the intervention. Functional outcome measures: Fugl-Meyer Assessment Scale - upper extremity (FMA-UE), Wolf Motor Function Test (WMFT), Nine-Hole Peg Test (NHPT), Arabic version of Stroke Impact Scale (SIS-16), and Stroke-Specific Measure of Adherence to Home-based Exercises (SS-MAHE). Physiological outcome measures: Cortical Excitability Assessment will be measured by Transcranial Magnetic Stimulation (TMS) with electromyographic (EMG) and functional magnetic resonance imaging (fMRI).

Study Timeline

• Study Start: 2023-04-11
• Status Verified: 2025-01
• Study First Submitted: 2025-01-02
• Study First Submitted QC: 2025-01-14
• Last Update Submitted: 2025-01-14
• Study First Posted: 2025-01-22
• Last Update Posted: 2025-01-22
• Primary Completion: 2025-04-11
• Study Completion: 2025-04-11

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 300

Inclusion Criteria

1. Adult participants clinically diagnosed and confirmed by imaging of ischemic or hemorrhagic cerebrovascular accident (Dahl et al., 2008; Jin et al., 2019).
2. Participant's age older than 18 years (Baltar et al., 2020).
3. Stroke onset more than 3 months with unilateral motor deficits (Lin et al., 2010).
4. Adequate cognitive function is required to follow instructions. The Arabic version of the Mini Mental State Examination (MMSE) should be ≥24 (Kim, 2021).
5. 10° of active extension to the metacarpophalangeal and interphalangeal joints and 20° at wrist will be assessed by manual goniometer (Dahl et al., 2008).
6. Fugl-Meyer assessment (FMA) scores between 19 and 58, indicating moderate to mild impairments.
7. Not participating in other clinical, or research studies at the same time.

Exclusion Criteria

1. Severe muscle spasticity at the affected limb at all joints (the Modified Ashworth Scale scores > 3) (Baltar et al., 2020).
2. Contraindications to NIBS (Bornheim et al., 2019).
3. Unilateral neglect (Dahl et al., 2008)
4. Other neurologic or orthopedic conditions that may affect hand function.
5. Unstable medical conditions.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Wolf Motor Function Test (WMFT)	at baseline and after intervention ( 4 weeks).	It is used to assess upper-limb performance through timed and functional tasks (Wolf et al., 2001). The WMFT is preferred to frequently used upper limb performance tests since it assesses a wide range of functional activities (from simple to complex) and investigates both performance time and movement quality (Morris et al., 2001). The modified WMFT consists of 17 items, 2 of which are strength measurements, and the remaining 15 items are functional tasks that gradually progress from simple movements in the proximal joint to complex movements in the distal joint. Each of the 15 tasks is timed to completion, up to a maximum of 120 seconds (Wolf et al., 2001). The items are scored on a 6-point scale ranging from 0 (does not attempt with the upper limb being tested) to 5 (uses the limb being tested, movement appears normal) (Wolf et al., 2005). A lower score indicates a lower functional level (Wolf et al., 2005).
Nine-Hole Peg Test (NHPT)	at baseline, and after 2 weeks, and after intervention ( 4 weeks).	The Nine-Hole Peg Test (NHPT) is one of the most commonly used performance tests for measuring hand function and manual dexterity in stroke patients (Chen et al., 2009; Mathiowetz et al., 1985). The NHPT consists of a container with nine pegs and a pegboard with nine holes. The board will be placed at the midline of the patient, with the container containing the pegs on the side of the hand being evaluated. The NHPT requires the patient to pick up the pegs from the container with the affected upper limb, transfer and insert them into the holes of the pegboard until it is full, and then return them to the container. Patients will be instructed to complete the test as quickly and accurately as possible (Sommerfeld et al., 2004). The score will be based on the time it takes to complete the test activity, which will be recorded in seconds. The stopwatch should be started when the patient touches the first peg until the last peg is put in the container (Oxford Grice et al., 2003).
Cortical Excitability Assessment	at baseline and after intervention ( 4 weeks).	The Transcranial Magnetic Stimulation (TMS) will be used to assess the corticospinal excitability through the measurement of the TMS-elicited motor evoked potential (MEP) in both the lesioned and the nonlesioned motor cortices (Wassermann et al., 2008). Online monitoring of the electromyographic (EMG) activity in response to TMS will be performed, MEPs will be recorded from the left and the right first interosseous (FDI) muscles
Functional magnetic resonance imaging (fMRI)	at baseline and after intervention ( 4 weeks).	Functional magnetic resonance imaging (fMRI) is a type of magnetic resonance imaging (MRI) that measures brain activity and connectivity. During an fMRI scan, a block design will be used. Each scan will take 6 minutes and be split into six blocks in the following order, with a rest of 30 seconds between each of the 15 contractions that last 2 seconds each and 30 seconds of rest in between (Wen et al., 2014). In each task, participants will be asked to grip a rubber ball at a target pressure of 30% of their maximum voluntary contraction using their affected hand (Cheng et al., 2021; Ismail et al., 2014). Visual feedback will be provided for the patients to guide the movement (Könönen et al., 2012).
Fugl-Meyer Assessment Scale - upper extremity (FMA-UE)	at baseline, and after 2 weeks, and after intervention (4 weeks).	The upper extremity domain of FMA consists of 33 items (reflex activity, volitional movement within synergies, volitional movement mixing synergies, volitional movement with little or no synergy, wrist, hand, coordination/ speed). On a 3-point ordinal scale, 0 = cannot perform, 1 = performs partially, and 2 = performs fully. The upper extremity domain has a total score of 66. A higher score indicated better performance of the affected side.

Secondary Outcome Measures

Name	Time	Method
Arabic version of Stroke Impact Scale (SIS-16)	at baseline, and after 2 weeks, and after intervention ( 4 weeks).	Stroke Impact Scale (SIS-16) is a stroke specific, self-reported outcome measure used to assess the impact of stroke on health-related quality of life status related to physical function (P. Duncan et al., 2003). It consists of 16 items, basic and instrumental activities of daily living (7 items), mobility (8 items), and hand function (1 item) on a 5-level Likert scale, 1 = inability to complete the item; 5 = not difficult at all (P. Duncan et al., 2003; P. W. Duncan et al., 2003). Higher scores indicate a better level of health-related quality of life status for stroke patients (P. W. Duncan et al., 2003).
Motor Activity log (MAL)	at baseline, week 1, week 2, week 3 and after intervention ( 4 weeks).	The MAL consists of two scales; amount of use (AOU), which is the amount the stroke patient uses on the affected limb, and quality of movement (QOM), which is the patient's perceived quality of movement while performing 30 items of daily life (Taub et al., 1993). The items are scored on a 6-point scale ranging from 0 (did not use my weaker arm) to 5 (used my weaker arm as often as before the stroke) for measuring AOU; and to measure QOM, the patient is asked how well the affected limb helped during this activity. Possible scores range from 0 (my weaker arm was not used at all for that activity) to 5 (the ability to use my weaker arm for that activity was as good as before the stroke) (Taub et al., 1993).

Trial Locations

Locations (1)

King Saud University Medical City; 🇸🇦 Riyadh, Saudi Arabia