NIBS With mCIMT for Motor and Functional Upper Limb Recovery in Stroke Patients.

Study Overview
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Brief Summary
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Stroke is one of the leading causes of serious long-term impairment. According to the estimates, 12,500 people suffer a new or recurrent ischemic stroke in Chile annually, which shows the magnitude of the problem. Motor impairment of the upper limb (UL) stands out as the principal sequel after a CVA (50% of the patients experience it), and the Constraint-Induced Movement Therapy (CIMT) is the rehabilitation approach that shows more scientific evidence today. Even though patients reach certain recuperation levels through this approach, results are still insufficient since 50-80% of the patients continue having upper limb motor impairment after completing standard rehabilitation. Because of this, it is pertinent to conduct research to explore new rehabilitation strategies to reduce the impairment indexes and to provide information for decision making based on evidence. Recent studies on functional neuroimaging propose that there is an abnormal balance in the motor cortex excitability after stroke - relative under-excitability in the affected hemisphere and over-excitability in the unaffected hemisphere (with the consequent inhibitory influence on ipsilesional regions) in stroke patient with moderate motor impairment. This imbalance in the hemispheres function would limit the possibilities of a greater recovery. Then, in order to reestablish brain balance, the investigators proposed that the early introduction of noninvasive techniques of brain stimulation, such as tDCS, to the motor rehabilitation training could promote improvement of upper limb function in patients with stroke. However, we lack studies that confirm the benefits of using these techniques, define the most appropriate protocols, and determine what patients and under which evolving stages would be the best candidates for treatment. This study aims to compare the effectiveness of seven days of bi-hemispheric tDCS, both active and sham, combined with modified CIMT (mCIMT) in the motor and functional recovery of the hemiparetic upper limb in hospitalized patients with subacute unihemispheric stroke at Hospital Clínico de la Universidad de Chile and Hospital San José. This comparison responds to the hypothesis that patients who receive bi-hemispheric and active tDCS combined with mCIMT (experimental group) get at least 30% more recovery of the paretic upper limb compared to the control group who receive sham bi-hemispheric tDCS plus mCIMT after a protocol of seven days treatment.

Detailed Description
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To test this hypothesis, the investigators propose to carry out a sham randomized multicenter double blind clinical trial. This trial considers seven continuous days of treatment when the participants with hemiparesis as a result of a stroke will be assigned to one of the treatment groups: bi-hemispheric tDCS combined with mCIMT or bi-hemispheric sham tDCS combined with mCIMT. Besides collecting demographic and clinical info from the subjects, the investigators will assess the patients using upper limb scales of functional motor recovery and an evaluation of their functional independence in basic activities of daily living (ADLs). STATA 14.0 software will be used for data analysis. To date, no study has tested the efficacy of early bi-hemispheric stimulation in combination with mCIMT in subacute hospitalized stroke patients.

Official Title
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Non-invasive Brain Stimulation Combined With Modified Constraint Induced Movement Therapy for Motor and Functional Upper Limb Recovery of Patients With Sub-acute Stroke: Multicenter Randomized Clinical Trial

Conditions
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Stroke, Upper Extremity Paresis, Electric Stimulation, Occupational Therapy

Intervention / Treatment
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* Device: Active Bihemispheric Transcranial direct current Stimulation
* Device: Sham Bihemispheric Transcranial direct current Stimulation
* Other: Modified Constraint Induced Movement Therapy


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: First unihemispheric stroke event, ischemic or hemorrhagic, cortical or subcortical. Hemiparesis with unilateral brachial compromise. Evolution time ≥ 2 days. (equal or more than 2 days after onset) Patient must be 18 years old or older. Showing ability to perform some movement with the upper limb: at least 20º active extension of the wrist and 10º extension in fingers and/or 20° abduction angle in the shoulder. Informed consent signed by the patient. Exclusion Criteria: Previous central injury with motor sequelae. Severe aphasia with a score ≥ 2 in the language item of the National Institutes of Health Stroke Scale assessment. Severe cognitive impairment with a score < 15 points in the Mini-mental state examination. Shoulder subluxation and/or pain > 4 points in the Visual Numeric Scale for pain. Non-controlled epilepsy or epileptic seizures in the last three months. Metal implants or pacemaker. Pregnancy. Any other condition that, in the responsible physician's opinion, could prevent the correct development of the treatment.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Sham randomized multicenter double clinical trial.
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Experimental Group<br>Active bi-hemispheric transcranial Direct Current Stimulation combined with modified Constraint Induced Movement Therapy. | Device: Active Bihemispheric Transcranial direct current Stimulation<br>* The session will start with the application of the with a couple of surface sponge electrodes (25-35 cm2) on the scalp. The treatment modality will be as follows: Active tDCS: The anodic electrode will be put on affected M1. The cathodic electrode will be put on contralateral M1. We will apply a constant current of 2mA of intensity during 20 minutes while the patient performs the occupational therapy session.<br>* Other names: Active tDCS;Other: Modified Constraint Induced Movement Therapy<br>* Both groups will perform the mCIMT during a period of seven consecutive days. This protocol consists of two elements: Restriction of the movements of the non-affected hand by wearing a mitt during six hours a day: we will use a mitt that limits the movement of the fingers but allows the free movements of the wrist, elbow, and shoulder. Intensive and individualized training of the affected arm during 2 hours a day guided by an occupational therapist: the two hours training will be divided into two sessions of one hour each. Sessions will be organized in three blocks: preparation, activation, and function. In the third block, devoted to function, the patient has to choose one activity of daily living that he wants to improve.<br>* Other names: mCIMT;|
| Sham Comparator: Control Group<br>Sham bi-hemispheric transcranial Direct Current Stimulation combined with modified Constraint Induced Movement Therapy. | Device: Sham Bihemispheric Transcranial direct current Stimulation<br>* The session will start with the application of the with a couple of surface sponge electrodes (25-35 cm2) on the scalp. The treatment modality will be as follows: Sham tDCS: We will use the same place and parameters of stimulation applied for the active group, but the stimulator will deactivate after 30 seconds of stimulation. This will ensure that the patient will feel the initial tingling sensation at the beginning of the tDCS which is a requisite for blinding. The occupational therapy session will last one hour.<br>* Other names: Sham tDCS;Other: Modified Constraint Induced Movement Therapy<br>* Both groups will perform the mCIMT during a period of seven consecutive days. This protocol consists of two elements: Restriction of the movements of the non-affected hand by wearing a mitt during six hours a day: we will use a mitt that limits the movement of the fingers but allows the free movements of the wrist, elbow, and shoulder. Intensive and individualized training of the affected arm during 2 hours a day guided by an occupational therapist: the two hours training will be divided into two sessions of one hour each. Sessions will be organized in three blocks: preparation, activation, and function. In the third block, devoted to function, the patient has to choose one activity of daily living that he wants to improve.<br>* Other names: mCIMT;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Upper Limb Motor Recovery. | Percentage of the upper limb motor recovery after seven days treatment as assessed by Fugl Meyer Upper Extremity. | 7 days. | 
| Upper Limb Functional Recovery. | Percentage of the upper limb functional recovery after seven days treatment as assessed by Wolf Motor Function Test. | 7 days. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Independence in basic activities of daily living. | Obtained score of independence in basic activities of daily living after seven days treatment as Assessed by Functional Independence Measure (FIM). | 10 days and 3 months later | 
| Upper Limb Motor Recovery. | Percentage maintenance of the upper limb motor recovery after seven days treatment as Assessed by Fugl Meyer Upper Extremity. | 10 days and 3 months later | 
| Upper Limb Functional Recovery. | Percentage maintenance of the upper limb functional recovery after seven days treatment as assessed by Wolf Motor Function Test. | 10 days | 
| Quality of life post-stroke | Score in quality of life with stroke impact scale | At the third month | 
| Brain activation patterns. | Effect on brain activation patterns of six patients after going through a protocol of seven days treatment. | 7 days. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Upper Extremity Paresis, Neuro Rehabilitation, tDCS, mCIMT, Occupational Therapy