Noninvasive Transcranial Direct Current Stimulation to Improve Executive Functions in Stroke Patients. MODUL-EXE Clinical Trial.

Study Overview
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Brief Summary
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This study will examine the possible effects of tDCS (Transcranial Direct Current Stimulation) treatment to the left DLPFC on executive functions in patients with an acute stroke affecting the frontal lobe or the basal ganglia. The study will include 40 acute stroke subjects. Participants will undergo a global cognitive assessment with the MoCA test and a specific assessment of executive functions with the abbreviated Wisconsin test, the five digit test and the digit span evaluation (a subtest from the Wechsler intelligence scale for adults-IV). Participants will then undergo real or sham stimulation with anodal tDCS combined with cognitive training of the main executive functions: working memory, inhibitory control and cognitive flexibility. After a 10-session intervention, a the baseline cognitive assessment will be repeated and subsequently, a follow-up of up to 12 months will be carried out.

Official Title
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Neuromodulation of Executive Dysfunction in Patients With Acute Stroke Using Transcranial Direct Current Stimulation. A Randomized-triple Blinded Controlled Clinical Trial. MODUL-EXE Trial.

Conditions
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Transcranial Direct Current Stimulation

Intervention / Treatment
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* Device: Transcranial Direct Current Stimulation (tDCS)
* Device: Sham Transcranial Direct current Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Clinical and radiological diagnosis, by means of cranial MRI or CT scan, of ischemic/hemorrhagic stroke, involving the frontal cortex or its subcortical connections (basal ganglia), in one or both hemispheres. The stroke occurred during the 3 months prior to inclusion in the study. Cognitive impairment with a dis-executive profile demonstrated by a score > 26 in the Spanish version of the MoCA test, adjusted for the number of years of formal education. Patients with functional independence prior to the stroke, defined as a modified rankin scale score < 3 points. The patient gives informed consent. Exclusion Criteria: Presence of other pathologies that may be a potential cause of disability or cognitive impairment. Moderate or severe aphasia that hinders communication. Severe sensory and/or motor impairments that prevent the completion of the evaluation and/or intervention processes. Presence of extensive vascular leukopathia (leukoaraiosis grade 3, 4). History of epilepsy or seizures. Presence of severe systemic pathology, including cardiac, hepatic or renal failure, active neoplasia. Failure to meet any of the inclusion criteria recorded in the Screening for electrical stimulation of the University of Göttingen. Presence of: Pacemaker. Electrical and/or metallic implants. Pregnancy. Anticonvulsant medication. Tattoos in the area of electrode placement.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anodal tDCS combined with cognitive training, stroke patients<br>To stimulate the left DLPFC, the anode electrode will be placed over F3 and the cathode will be placed over the right supraorbital region (Fp2). Each stimulation will be applied for 20 min at 2mA intensity. Stimulation will be continued with the performance of three cognitive training exercises specifically designed to improving working memory, inhibitory control and cognitive flexibility. | Device: Transcranial Direct Current Stimulation (tDCS)<br>* Real anodal tDCS over the left dorsolateral prefrontal cortex in acute stroke patients to improve dysexecutive syndrome. Intensity: 2 mA. Stimulation period: 20 minutes.<br>|
| Sham Comparator: Sham tDCS combined with cognitive training, stroke patients<br>To stimulate the left DLPFC, the anode electrode will be placed over F3 and the cathode will be placed over the right supraorbital region (Fp2). Each stimulation will be applied for 1 min at 2mA intensity (sham stimulation). Stimulation will be continued with the performance of three cognitive training exercises specifically designed to improving working memory, inhibitory control and cognitive flexibility. | Device: Sham Transcranial Direct current Stimulation<br>* Sham anodal tDCS over the left dorsolateral prefrontal cortex: anodal tDCS. Intensity: 2 mA. Stimulation period: 1 minute. Afterwards, the device will automatically shut down but the sham stimulation period will last a total of 20 minutes.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Montreal cognitive assessment | Global cognitive assessment test that incorporates the evaluation of executive domains such as working memory, inhibition and others such as verbal fluency, delayed recall and visuospatial capacity. Maximum score: 30. Normal if score > 26. | Evaluation immediately post intervention | 
| Montreal cognitive assessment | Global cognitive assessment test that incorporates the evaluation of executive domains such as working memory, inhibition and others such as verbal fluency, delayed recall and visuospatial capacity | Evaluation post intervention: One month after intervention | 
| Montreal cognitive assessment | Global cognitive assessment test that incorporates the evaluation of executive domains such as working memory, inhibition and others such as verbal fluency, delayed recall and visuospatial capacity | Post intervention: Three months after intervention | 
| Montreal cognitive assessment | Global cognitive assessment test that incorporates the evaluation of executive domains such as working memory, inhibition and others such as verbal fluency, delayed recall and visuospatial capacity | Post intervention: Six months after intervention | 
| Digit Span test | Evaluates working memory. Normal average reference: to have a digit span of 7 items (plus or minus 2), the greater the memory span, the better the result. | Evaluation immediately post intervention | 
| Digit Span test | Evaluates working memory. Normal average reference: to have a digit span of 7 items (plus or minus 2), the greater the memory span, the better the result. | Evaluation post intervention: One month after intervention | 
| Digit Span test | Evaluates working memory. Normal average reference: to have a digit span of 7 items (plus or minus 2), the greater the memory span, the better the result. | Post intervention: Three months after intervention | 
| Digit Span test | Evaluates working memory. Normal average reference: to have a digit span of 7 items (plus or minus 2), the greater the memory span, the better the result. | Post intervention: Six months after intervention | 
| Wisconsin Card Sorting Test, Brief version. | Assess cognitive flexibility. Respondents are required to sort numbered response cards according to different principles and to alter their approach during test administration. The global number of categories achieved will be assesed, the greater, the better the result is. | Evaluation immediately post intervention | 
| Wisconsin Card Sorting Test, Brief version. | Assess cognitive flexibility. Respondents are required to sort numbered response cards according to different principles and to alter their approach during test administration. The global number of categories achieved will be assesed, the greater, the better the result is. | Evaluation post intervention: One month after intervention | 
| Wisconsin Card Sorting Test, Brief version. | Assess cognitive flexibility. Respondents are required to sort numbered response cards according to different principles and to alter their approach during test administration. The global number of categories achieved will be assesed, the greater, the better the result is. | Post intervention: Three months after intervention | 
| Wisconsin Card Sorting Test, Brief version. | Assess cognitive flexibility. Respondents are required to sort numbered response cards according to different principles and to alter their approach during test administration. The global number of categories achieved will be assesed, the greater, the better the result is. | Post intervention: Six months after intervention | 
| Five digit test | Assessing inhibitory control. A numerical task divided into four components. The first component (reading) demands subjects to name numbers from 1 to 5 as fast as they can. On the second component (counting), they need to describe quantities from 1 to 5. The third component (choosing) involves a selective attention trial, where the subjects must not read the numbers, but rather tell how many numbers are present in each stimulus, in an incongruent condition. The last component (shifting) is similar to the choosing trial, but for each of the five stimuli, there is one previously where the subject must read the stimulus numbers. The test total scores will be used as the main measure in this study. Higher scores indicate worse performance. | Evaluation immediately post intervention | 
| Five digit test | Assessing inhibitory control. A numerical task divided into four components. The first component (reading) demands subjects to name numbers from 1 to 5 as fast as they can. On the second component (counting), they need to describe quantities from 1 to 5. The third component (choosing) involves a selective attention trial, where the subjects must not read the numbers, but rather tell how many numbers are present in each stimulus, in an incongruent condition. The last component (shifting) is similar to the choosing trial, but for each of the five stimuli, there is one previously where the subject must read the stimulus numbers. The test total scores will be used as the main measure in this study. Higher scores indicate worse performance. | Evaluation post intervention: One month after intervention | 
| Five digit test | Assessing inhibitory control. A numerical task divided into four components. The first component (reading) demands subjects to name numbers from 1 to 5 as fast as they can. On the second component (counting), they need to describe quantities from 1 to 5. The third component (choosing) involves a selective attention trial, where the subjects must not read the numbers, but rather tell how many numbers are present in each stimulus, in an incongruent condition. The last component (shifting) is similar to the choosing trial, but for each of the five stimuli, there is one previously where the subject must read the stimulus numbers. The test total scores will be used as the main measure in this study. Higher scores indicate worse performance. | Post intervention: Three months after intervention | 
| Five digit test | Assessing inhibitory control. A numerical task divided into four components. The first component (reading) demands subjects to name numbers from 1 to 5 as fast as they can. On the second component (counting), they need to describe quantities from 1 to 5. The third component (choosing) involves a selective attention trial, where the subjects must not read the numbers, but rather tell how many numbers are present in each stimulus, in an incongruent condition. The last component (shifting) is similar to the choosing trial, but for each of the five stimuli, there is one previously where the subject must read the stimulus numbers. The test total scores will be used as the main measure in this study. Higher scores indicate worse performance. | Post intervention: Six months after intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| modified rankin scale | Functional assessment scale ranging from 0 (independent) to 6 (death) | Evaluation immediately post intervention | 
| modified rankin scale | Functional assessment scale ranging from 0 (independent) to 6 (death) | Evaluation post intervention: One month after intervention | 
| modified rankin scale | Functional assessment scale ranging from 0 (independent) to 6 (death) | Post intervention: Three months after intervention | 
| modified rankin scale | Functional assessment scale ranging from 0 (independent) to 6 (death) | Post intervention: Six months after intervention | 
| modified rankin scale | Functional assessment scale ranging from 0 (independent) to 6 (death) | Post intervention: 12 months after intervention | 
| Return to work | To determine whether the patient has been able to return to the previous job | Post intervention: One month after intervention | 
| Return to work | To determine whether the patient has been able to return to the previous job | Post intervention: Three months after intervention | 
| Return to work | To determine whether the patient has been able to return to the previous job | Post intervention: 6 months after intervention | 
| Return to work | To determine whether the patient has been able to return to the previous job | Post intervention: 12 months after intervention | 
| Beck's Depression Inventory | Evaluation of depression ranging from 0 to 63. A score > 20: significant depression (moderate-severe) | Evaluation immediately post intervention | 
| Beck's Depression Inventory | Evaluation of depression ranging from 0 to 63. A score > 20: significant depression | Post intervention: One month after intervention | 
| Beck's Depression Inventory | Evaluation of depression ranging from 0 to 63. A score > 20: significant depression | Post intervention: Three months after intervention | 
| Beck's Depression Inventory | Evaluation of depression ranging from 0 to 63. A score > 20: significant depression | Post intervention: Six months after intervention | 
| Apathy Evaluation Scale | Evaluation of presence of apathy. Consists of 18 specific items to quantify apathy within a scoring range of 18 to 72. The greater the score, the greater the apathy symptoms. | Evaluation immediately post intervention | 
| Apathy Evaluation Scale | Evaluation of presence of apathy. Consists of 18 specific items to quantify apathy within a scoring range of 18 to 72. The greater the score, the greater the apathy symptoms. | Post intervention: One month after intervention | 
| Apathy Evaluation Scale | Evaluation of presence of apathy. Consists of 18 specific items to quantify apathy within a scoring range of 18 to 72. The greater the score, the greater the apathy symptoms. | Post intervention: Three months after intervention | 
| Apathy Evaluation Scale | Evaluation of presence of apathy. Consists of 18 specific items to quantify apathy within a scoring range of 18 to 72. The greater the score, the greater the apathy symptoms. | Post intervention: Six months after intervention | 
| WHOQOL-BREF scale | Evaluation of quality of life. There are no proposed cut-off points. The higher the score, the higher the quality of life. | Evaluation immediately post intervention | 
| WHOQOL-BREF scale | Evaluation of quality of life. There are no proposed cut-off points. The higher the score, the higher the quality of life. | Post intervention: One month after intervention | 
| WHOQOL-BREF scale | Evaluation of quality of life. There are no proposed cut-off points. The higher the score, the higher the quality of life. | Post intervention: Three months after intervention | 
| WHOQOL-BREF scale | Evaluation of quality of life. There are no proposed cut-off points. The higher the score, the higher the quality of life. | Post intervention: Six months after intervention |