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

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

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.

Study Overview

• Status: Recruiting
• Conditions: Stroke, Chronic
• Intervention / Treatment: Device: Transcranial direct current stimulation (tDCS dualsite) + dual-task traning; Device: Transcranial direct current stimulation sham + dual-task training; Device: Transcranial direct current stimulation (Anodal tDCS) + dual-task training

Detailed Description

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.

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

Contacts and Locations

• Study Contact: Name: Suellen Andrade; Phone Number: +5583999805189; Email: suellenandrade@gmail.com

Study Locations

• Brazil
  • Paraíba
    • João Pessoa, Paraíba, Brazil, 58051-900
      • Recruiting
      • Federal University of Paraíba,Department of Psychology

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 90 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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;

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Group 1 - anodal tDCS; 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; 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.; Other Names: tDCS dualsite; Device: Transcranial direct current stimulation sham + dual-task training; 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.; Other Names: tDCS sham
Active Comparator: Group 2 - tDCS dualsite; 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 sham + dual-task training; 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.; Other Names: tDCS sham; Device: Transcranial direct current stimulation (Anodal tDCS) + dual-task training; 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.; Other Names: anodal tDCS
Placebo Comparator: Group 3 - tDCS sham; 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 (tDCS dualsite) + dual-task traning; 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.; Other Names: tDCS dualsite; Device: Transcranial direct current stimulation (Anodal tDCS) + dual-task training; 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.; Other Names: anodal tDCS

What is the study measuring?

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.

Collaborators and Investigators

• Sponsor: Federal University of Paraíba

Study record dates

Study Major Dates

• Study Start (Actual): March 10, 2022
• Primary Completion (Anticipated): December 24, 2022
• Study Completion (Anticipated): December 24, 2022

Study Registration Dates

• First Submitted: March 24, 2021
• First Submitted That Met QC Criteria: April 14, 2021
• First Posted (Actual): April 20, 2021

Study Record Updates

• Last Update Posted (Actual): April 28, 2022
• Last Update Submitted That Met QC Criteria: April 21, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: Stroke; Transcranial direct current stimulation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Stroke
• Other Study ID Numbers: AVCtDCS

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No