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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Transcranial Direct Current Stimulation
• Intervention / Treatment: Device: Transcranial Direct Current Stimulation (tDCS); Device: Sham Transcranial Direct current Stimulation

• Study Type: Interventional
• Enrollment (Anticipated): 40
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Laura Amaya Pascasio, MD; Phone Number: +34 950016860; Email: laura.amaya.pascasio@gmail.com

Study Locations

• Spain
  • Almeria
    • Almería, Almeria, Spain, 04009
      • Recruiting
      • Torrecárdenas University Hospital
      • Contact: Laura. Amaya Pascasio, M.D.; Phone Number: 605965362; Email: laura.amaya.pascasio@gmail.com
      • Contact: Patricia Martinez Sanchez, PhD; Email: patrinda@ual.es

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 70 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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:

  1. Pacemaker.
  2. Electrical and/or metallic implants.
  3. Pregnancy.
  4. Anticonvulsant medication.
  5. Tattoos in the area of electrode placement.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Anodal tDCS combined with cognitive training, stroke patients; 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); Real anodal tDCS over the left dorsolateral prefrontal cortex in acute stroke patients to improve dysexecutive syndrome. Intensity: 2 mA. Stimulation period: 20 minutes.
Sham Comparator: Sham tDCS combined with cognitive training, stroke patients; 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; 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.

What is the study measuring?

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: Six months after intervention
modified rankin scale	Functional assessment scale ranging from 0 (independent) to 6 (death)	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
modified rankin scale	Functional assessment scale ranging from 0 (independent) to 6 (death)	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: 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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in resting state functional connectivity	functional near-infrared spectroscopy-fNIRS	Evaluation immediately post intervention
Change in resting state functional connectivity	functional near-infrared spectroscopy-fNIRS	Post intervention: One month after intervention
Change in resting state functional connectivity	functional near-infrared spectroscopy-fNIRS	Post intervention: Three months after intervention
Change in resting state functional connectivity	functional near-infrared spectroscopy-fNIRS	Post intervention: Six months after intervention
Motor evaluation	Nine-hole peg test and Timed 25-Foot Walk tests as motor status monitoring tasks	Evaluation immediately post intervention
Motor evaluation	Nine-hole peg test and Timed 25-Foot Walk tests as motor status monitoring tasks	Post intervention: One month after intervention
Motor evaluation	Nine-hole peg test and Timed 25-Foot Walk tests as motor status monitoring tasks	Post intervention: Three months after intervention
Motor evaluation	Nine-hole peg test and Timed 25-Foot Walk tests as motor status monitoring tasks	Post intervention: Six months after intervention
Blood biomarkers	Brain-derived neurotrophic factor (BDNF), glial cell-derived neurotrophic factor (GDNF), nerve growth factor (NGF), pituitary adenylate cyclase polypeptide 38 (PACAP-38), insulin-like growth factor type 1 (IGF-1), interleukins 2, 4, 6, 8 and 10; and tumour necrosis factor (TNF).	Evaluation immediately post intervention

Collaborators and Investigators

• Sponsor: Fundación Pública Andaluza para la Investigación Biomédica Andalucía Oriental
• Collaborators: Instituto de Salud Carlos III; Universidad de Almeria
• Investigators: Principal Investigator: Patricia Martinez Sanchez, PhD, Torrecárdenas University Hospital; Study Director: Pilar Flores Cubos, Professor, PhD, Department of Psychology. University of Almeria

Study record dates

Study Major Dates

• Study Start (Actual): February 15, 2022
• Primary Completion (Anticipated): December 30, 2023
• Study Completion (Anticipated): December 30, 2024

Study Registration Dates

• First Submitted: November 8, 2022
• First Submitted That Met QC Criteria: November 23, 2022
• First Posted (Actual): November 29, 2022

Study Record Updates

• Last Update Posted (Actual): January 18, 2023
• Last Update Submitted That Met QC Criteria: January 13, 2023
• Last Verified: January 1, 2023

More Information

Terms related to this study

• Other Study ID Numbers: MODUL-EXE

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No