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

Official title

Neurophysiological and Behavioral Effects of Combining Transcranial Direct Current Stimulation (tDCS) and Modified-Constraint Induced Movement Therapy (mCIMT) on Upper Limb Function Recovery in Patients with Stroke

Overview

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).

Interventions

• Device Anodal tDCS combined with mCIMT
  20 minutes of anodal tDCS followed by 1 hour of the mCIMT program. The anodal electrode will be placed over the ipsilesional M1 (primary motor cortex, C3 or C4 according to EEG 10/20 system), and the cathodal electrode over the contralateral supraorbital area (Fp1 or Fp2) ). Leading to subthreshold depolarization to promote cortical excitation. And twelve different oriented tasks will be used during the 1-hour training period.
• Device Cathodal tDCS combined with mCIMT
  20 minutes of cathodal tDCS followed by 1 hour of the mCIMT program. the cathodal electrode will be placed over the contralesional M1, and the anodal electrode over the contralateral supraorbital area (Fp1 or Fp2). leading to subthreshold polarization to promote cortical inhibition. And twelve different oriented tasks will be used during the 1-hour training period.
• Device Bihemispheric tDCS combined with mCIMT
  20 minutes of Bihemispheric tDCS followed by 1 hour of the mCIMT program. the cathodal electrode will be placed over the primary motor cortex (M1) of the contralesional hemisphere and the anodal electrode will be placed above the ipsilateral M1 position (C3 or C4 positions, according to the 10/20 EEG system). And twelve different oriented tasks will be used during the 1-hour training period.
• Device Sham tDCS combined with mCIMT
  20 minutes of sham tDCS followed by 1 hour of the mCIMT program. the same stimulation place and parameters will be used as in the anodal group. However, after 30 seconds of stimulation, the stimulator will switch off. This provides the participants with the experience of the initial itchy sensation that occurs during tDCS, which is required for efficient masking. And twelve different oriented tasks will be used during the 1-hour training period.

Primary outcome measures

• Fugl-Meyer Assessment Scale - upper extremity (FMA-UE) [Time frame: at baseline, and after 2 weeks, and after intervention (4 weeks).]
• Wolf Motor Function Test (WMFT) [Time frame: at baseline, and after 2 weeks, and after intervention ( 4 weeks).]
• Nine-Hole Peg Test (NHPT) [Time frame: at baseline, and after 2 weeks, and after intervention ( 4 weeks).]
• Cortical Excitability Assessment [Time frame: at baseline and after intervention ( 4 weeks).]
• Functional magnetic resonance imaging (fMRI) [Time frame: at baseline and after intervention ( 4 weeks).]
• Wolf Motor Function Test (WMFT) [Time frame: at baseline and after intervention ( 4 weeks).]

Secondary outcome measures (2)

• Arabic version of Stroke Impact Scale (SIS-16) [Time frame: at baseline, and after 2 weeks, and after intervention ( 4 weeks).]
• Motor Activity log (MAL) [Time frame: at baseline, week 1, week 2, week 3 and after intervention ( 4 weeks).]

Eligibility criteria

Inclusion criteria

• Adult participants clinically diagnosed and confirmed by imaging of ischemic or hemorrhagic cerebrovascular accident (Dahl et al., 2008; Jin et al., 2019).
• Participant's age older than 18 years (Baltar et al., 2020).
• Stroke onset more than 3 months with unilateral motor deficits (Lin et al., 2010).
• Adequate cognitive function is required to follow instructions. The Arabic version of the Mini Mental State Examination (MMSE) should be ≥24 (Kim, 2021).
• 10° of active extension to the metacarpophalangeal and interphalangeal joints and 20° at wrist will be assessed by manual goniometer (Dahl et al., 2008).
• Fugl-Meyer assessment (FMA) scores between 19 and 58, indicating moderate to mild impairments.
• 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) (Baltar et al., 2020).
• Contraindications to NIBS (Bornheim et al., 2019).
• Unilateral neglect (Dahl et al., 2008)
• Other neurologic or orthopedic conditions that may affect hand function.
• Unstable medical conditions.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Double blind

Primary purpose

Treatment

Study locations

Saudi Arabia · 1 center

• King Saud University Medical City — Riyadh

Publications

• Baltar A, Piscitelli D, Marques D, Shirahige L, Monte-Silva K. Baseline Motor Impairment Predicts Transcranial Direct Current Stimulation Combined with Physical Therapy-Induced Improvement in Individuals with Chronic Stroke. Neural Plast. 2020 Nov 25;2020:8859394. doi: 10.1155/2020/8859394. eCollection 2020. PMID 33299400

Identifiers

NCT: NCT06786000 · E-23-7495

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗