Effects of Dualsite Anodic tDCS on Lower Limbs Function in Patients After Stroke: Randomized, Double-blind, Placebo-controlled, Crossover Trial

Study Overview
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Brief Summary
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It is currently known that Transcranial Direct Current Stimulation (tDCS) can modulate cortical activity, being considered an important resource in the treatment of sequelae resulting from stroke. However, evidence of the effects of tDCS on lower limb motor recovery after stroke remains scarce and inconclusive. Furthermore, little is known about the effects of dualsite tDCS in chronic patients. Therefore, the present study seeks to compare the effects of conventional anodic tDCS (M1) with double-site/dualsite anodic tDCS (M1 + DLPFC) and simulated tDCS on lower limb motor function in patients after ischemic stroke in a chronic stage. The study is a randomized, double-blind, placebo-controlled, crossover clinical trial with subjects after stroke. After recruitment and initial screening, participants will be randomized into three groups: G1: anodic tDCS - participants who will receive real current over the primary motor area; G2: dualsite tDCS - participants who will receive real current over the primary motor area and dorsolateral prefrontal area (DLPFC) and G3: simulated tDCS - participants who will receive simulated stimulation. Participants will receive 10 tDCS sessions, for 20 minutes, associated with a physical therapy protocol based on a dual motor and cognitive task, on alternate days (3 times a week). In each phase of the study, pre- and post-intervention evaluations will be carried out, the evaluated outcomes will be: motor function (Fugl-Meyer Scale), functional connectivity (EEG), quality of life (EQ-5D), level of functional disability ( Rankin Scale), static balance (Biodex Balance System) and cognitive function (MoCA). Statistical analyzes will be performed using SPSS software (Version 20.0) and MATLAB 9.2.0 with a significance level of p <0.05.

Detailed Description
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Participants will be divided into 03 groups: G1: anodic tDCS - participants who will receive real current over the primary motor area; G2: dualsite tDCS - participants who will receive real current over the primary motor area and over the dorsolateral prefrontal area (DLPFC) and G3: simulated tDCS - participants who will receive simulated stimulation. Participants will be entered into the study through the eligibility criteria and will be randomly allocated, with block exchange at a rate of 1:1:1. In each phase of the study, participants will receive 10 tDCS sessions, for 20 minutes, on alternate days (3 times a week, excluding weekends). The TCT-Research neurostimulator will be used for stimulation. The electrodes will be positioned according to the 10-20 international electroencephalogram classification system. Electrodes wrapped in sponges, moistened with saline solution (0.9% NaCl) will be used. The applied current will be 2mA (5x5 cm active electrodes; 25 cm2; current density of 0.08 mA/cm2). For group 1 (anodic tDCS) the anodic electrode (5x5 cm) will be applied to the primary motor area (C3/C4) ipsilateral to the lesion and the reference electrode (6x9 cm) to the deltoid muscle region. In group 2 (dualsite tDCS) two active electrodes (5x5 cm) will be used, which will be positioned over the primary motor area (C3/C4) and over the dorsolateral prefrontal cortex (F3 or F4) in the ipsilateral hemisphere. For this stimulation modality, two active electrodes (anodic) and a reference electrode (6x9 cm) will be used on the deltoid muscle region. For group 3 (simulated tDCS) the positioning of the electrodes will be the same as for group 1, however the device will be configured in sham mode in which the current will cease 30 seconds after the start of stimulation, in this way the effects of active stimulation will be simulated and the participants will perceive the sensations typically felt, but without the induction of clinical effects (Nitsche & Paulus, 2000). At the end of each session, participants will be asked to report any unpleasant effects and asked about possible adverse effects. In addition, all participants will be blind to the type of stimulation they will receive.

Official Title
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Effects of Dualsite Anodic tDCS on Lower Limbs Function in Patients After Stroke

Conditions
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Stroke, Chronic

Intervention / Treatment
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* Device: Transcranial direct current stimulation (Anodal tDCS) + dual-task training
* Device: Transcranial direct current stimulation (tDCS dualsite) + dual-task traning
* Device: Transcranial direct current stimulation sham + dual-task training


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Single episode of unilateral, ischemic stroke in middle cerebral artery proven by means of magnetic resonance imaging or computed tomography. Classification of brain injury based on the criteria: Oxfordshire Community Stroke Project (OCSP) or Trial of Org 10172 in Acute Stroke Treatment (TOAST); Patients in the chronic stage (after six months after the injury) Individuals over 18 years of age; Both sexes; Absence of mental disorders, assessed using the Self Reporting Questionnaire (SRQ-20), with a cut-off point of 7/8 points. Absence of cognitive deficits, assessed using the Mini Mental State Examination (MMSE> 24). Patients with mild to moderate degree of injury severity (NIHHS <17 points). Exclusion Criteria: Patients with other associated pathologies that can influence motor activity (example: traumatic brain injury, brain tumor); •- Participants unable to complete the initial assessment due to severe aphasia (Token Test <17); habitual use of drugs or alcohol; Use of drugs that modulate the activity of the Central Nervous System; Gestation; Use of metallic / electronic implants and / or cardiac pacemakers;

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: Group 1 - anodal tDCS<br>Participants will receive 10 tDCS sessions, for 20 minutes, on days alternate (3 times a week). The neurostimulator TCT-Research will be used for stimulation. The electrodes will be positioned according to the international classification system of the electroencephalogram 10/20. For group 1 (anodic tDCS) the anodic electrode (5x5 cm) will be applied to the primary motor area (C3/C4) ipsilateral to the lesion and the reference electrode (6x9 cm) to the deltoid muscle region. Simultaneously with the tDCS sessions, participants will be submitted to a physical therapy protocol based on motor and cognitive dual-task training. Each task will have a duration of 3 minutes, followed by a rest period of 30s. | Device: Transcranial direct current stimulation (tDCS dualsite) + dual-task traning<br>* tDCS dualsite 837 / 5.000 Resultados de tradução Simultaneously with the tDCS sessions, participants will be submitted to a physical therapy protocol based on motor and cognitive dual-task training, which will include: (1) walking repeating phrases spoken by the researcher; (2) walking counting numbers in ascending order; (3) walk while counting the numbers in descending order; (4) walking during the execution of a string of words; (5) Walking while listening to a list of fruits and saying YES when hearing the word strawberry and (6) walking reciting a phrase backwards. Each task will have a duration of 3 minutes, followed by a rest period of 30s. The tasks will be performed performing forward, side and back march. Subjects will be instructed to focus on both tasks. The training will have a total duration of 20 minutes in each session.<br>* Other names: tDCS dualsite;Device: Transcranial direct current stimulation sham + dual-task training<br>* tDCS sham 837 / 5.000 Resultados de tradução Simultaneously with the tDCS sessions, participants will be submitted to a physical therapy protocol based on motor and cognitive dual-task training, which will include: (1) walking repeating phrases spoken by the researcher; (2) walking counting numbers in ascending order; (3) walk while counting the numbers in descending order; (4) walking during the execution of a string of words; (5) Walking while listening to a list of fruits and saying YES when hearing the word strawberry and (6) walking reciting a phrase backwards. Each task will have a duration of 3 minutes, followed by a rest period of 30s. The tasks will be performed performing forward, side and back march. Subjects will be instructed to focus on both tasks. The training will have a total duration of 20 minutes in each session.<br>* Other names: tDCS sham;|
| Active Comparator: Group 2 - tDCS dualsite<br>Participants will receive 10 tDCS sessions, for 20 minutes, on days alternate (3 times a week). The neurostimulator TCT-Research will be used for stimulation. The electrodes will be positioned according to the international classification system of the electroencephalogram 10/20. In group 2 (dualsite tDCS) two active electrodes (5x5 cm) will be used, which will be positioned over the primary motor area (C3/C4) and over the dorsolateral prefrontal cortex (F3 or F4) in the ipsilateral hemisphere. For this stimulation modality, two active electrodes (anodic) and a reference electrode (6x9 cm) will be used on the deltoid muscle region. Simultaneously with the tDCS sessions, participants will be submitted to a physical therapy protocol based on motor and cognitive dual-task training. Each task will have a duration of 3 minutes, followed by a rest period of 30s. | Device: Transcranial direct current stimulation (Anodal tDCS) + dual-task training<br>* anodal tDCS 837 / 5.000 Resultados de tradução Simultaneously with the tDCS sessions, participants will be submitted to a physical therapy protocol based on motor and cognitive dual-task training, which will include: (1) walking repeating phrases spoken by the researcher; (2) walking counting numbers in ascending order; (3) walk while counting the numbers in descending order; (4) walking during the execution of a string of words; (5) Walking while listening to a list of fruits and saying YES when hearing the word strawberry and (6) walking reciting a phrase backwards. Each task will have a duration of 3 minutes, followed by a rest period of 30s. The tasks will be performed performing forward, side and back march. Subjects will be instructed to focus on both tasks. The training will have a total duration of 20 minutes in each session.<br>* Other names: anodal tDCS;Device: Transcranial direct current stimulation sham + dual-task training<br>* tDCS sham 837 / 5.000 Resultados de tradução Simultaneously with the tDCS sessions, participants will be submitted to a physical therapy protocol based on motor and cognitive dual-task training, which will include: (1) walking repeating phrases spoken by the researcher; (2) walking counting numbers in ascending order; (3) walk while counting the numbers in descending order; (4) walking during the execution of a string of words; (5) Walking while listening to a list of fruits and saying YES when hearing the word strawberry and (6) walking reciting a phrase backwards. Each task will have a duration of 3 minutes, followed by a rest period of 30s. The tasks will be performed performing forward, side and back march. Subjects will be instructed to focus on both tasks. The training will have a total duration of 20 minutes in each session.<br>* Other names: tDCS sham;|
| Placebo Comparator: Group 3 - tDCS sham<br>Participants will receive 10 tDCS sessions, for 20 minutes, on days alternate (3 times a week). The neurostimulator TCT-Research will be used for stimulation. The electrodes will be positioned according to the international classification system of the electroencephalogram 10/20. For group 3 (simulated tDCS) the positioning of the electrodes will be the same as for group 1, however the device will be configured in sham mode in which the current will cease 30 seconds after the start of stimulation. Simultaneously with the tDCS sessions, participants will be submitted to a physical therapy protocol based on motor and cognitive dual-task training. Each task will have a duration of 3 minutes, followed by a rest period of 30s. | Device: Transcranial direct current stimulation (Anodal tDCS) + dual-task training<br>* anodal tDCS 837 / 5.000 Resultados de tradução Simultaneously with the tDCS sessions, participants will be submitted to a physical therapy protocol based on motor and cognitive dual-task training, which will include: (1) walking repeating phrases spoken by the researcher; (2) walking counting numbers in ascending order; (3) walk while counting the numbers in descending order; (4) walking during the execution of a string of words; (5) Walking while listening to a list of fruits and saying YES when hearing the word strawberry and (6) walking reciting a phrase backwards. Each task will have a duration of 3 minutes, followed by a rest period of 30s. The tasks will be performed performing forward, side and back march. Subjects will be instructed to focus on both tasks. The training will have a total duration of 20 minutes in each session.<br>* Other names: anodal tDCS;Device: Transcranial direct current stimulation (tDCS dualsite) + dual-task traning<br>* tDCS dualsite 837 / 5.000 Resultados de tradução Simultaneously with the tDCS sessions, participants will be submitted to a physical therapy protocol based on motor and cognitive dual-task training, which will include: (1) walking repeating phrases spoken by the researcher; (2) walking counting numbers in ascending order; (3) walk while counting the numbers in descending order; (4) walking during the execution of a string of words; (5) Walking while listening to a list of fruits and saying YES when hearing the word strawberry and (6) walking reciting a phrase backwards. Each task will have a duration of 3 minutes, followed by a rest period of 30s. The tasks will be performed performing forward, side and back march. Subjects will be instructed to focus on both tasks. The training will have a total duration of 20 minutes in each session.<br>* Other names: tDCS dualsite;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fugl-Meyer assessment (FMA) pre-intervention (T0) | Fugl-Meyer assessment (FMA) for lower limbs pre-intervention (T0) | The evaluations will be carried out in pre-intervention (T0) | 
| Fugl-Meyer assessment (FMA) after the stimulation protocol (T1) | Fugl-Meyer assessment (FMA) for lower limbs after the stimulation protocol (T1) | The T1 assessment will be performed up to one week after the stimulation protocol is completed. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Functional connectivity (EEG) pre-intervention (T0) | The functional connectivity of the target network will be assessed, through the acquisition of the EEG | The evaluations will be carried out in pre-intervention (T0) | 
| Functional connectivity (EEG) after the stimulation protocol (T1) | The functional connectivity of the target network will be assessed, through the acquisition of the EEG | The T1 assessment will be performed up to one week after the stimulation protocol is completed. | 
| EQ-5D (T0) | Quality of life. Presenting a final score from 0 to 100, where 0 corresponds to the worst general state of health and 100 the best state of health. | The evaluations will be carried out in pre-intervention (T0). | 
| EQ-5D (T1) | Quality of life.Presenting a final score from 0 to 100, where 0 corresponds to the worst general state of health and 100 the best state of health. | The T1 assessment will be performed up to one week after the stimulation protocol is completed. | 
| Modified Rankin Scale pre-intervention (T0) | Functional disability. The score on the Rankin scale ranges from 0 to 6, in order to assess the patient's neurological condition, in which the higher the value, the worse the condition. 0 - No symptoms - No significant disabilities - Mild disability - Moderate disability - Moderate-severe disability - Severe disability - Death | The evaluations will be carried out in pre-intervention (T0). | 
| Modified Rankin Scale after the stimulation protocol (T1) | Functional disability. The score on the Rankin scale ranges from 0 to 6, in order to assess the patient's neurological condition, in which the higher the value, the worse the condition. 0 - No symptoms - No significant disabilities - Mild disability - Moderate disability - Moderate-severe disability - Severe disability - Death | The T1 assessment will be performed up to one week after the stimulation protocol is completed. | 
| Balance | Biodex Balance System (BBS) | The T0 assessment will be performed up to one week after the stimulation protocol is completed. | 
| Balance | Biodex Balance System (BBS) | The T1 assessment will be performed up to one week after the stimulation protocol is completed. | 
| MoCA | Cognitive function | The T0 assessment will be performed up to one week after the stimulation protocol is completed. | 
| MoCA | Cognitive function | The T1 assessment will be performed up to one week after the stimulation protocol is completed. | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Stroke, Transcranial direct current stimulation