Neuroregeneration Enhanced by Transcranial Direct Current Stimulation (TDCS) in Stroke

Study Overview
=================
Brief Summary
-----------------
Testing the hypothesis that non-invasive brain stimulation by transcranial direct current stimulation (tDCS) combined with functional training in the subacute phase of first-ever stroke will enhance functional regeneration compared with a Placebo intervention.

Detailed Description
-----------------
Stroke is the leading cause of long-term disability, which significantly impairs the economic and social life of patients and society. Every year 200 000 to 250 000 patients suffer a stroke in Germany. Only a small number of the stroke survivors recover to a degree that allows them to return into their professional and private life. Despite significant efforts to develop novel and efficient treatment strategies the level of functional regeneration is still not satisfying. Thus, the development of innovative and effective treatment strategies will have a major impact for the patients' life, the society and the public health system. Within the proposed project an innovative, non-invasive and cost effective interventional strategy, based on the combination of a specific rehabilitative training and brain stimulation by transcranial direct current stimulation (tDCS), will be used to enhance functional regeneration in stroke patients. The intervention will be applied in an early stage in which plasticity, cortical reorganization and functional improvement is most pronounced. We hypothesize that the combination of anodal tDCS delivered to the motor cortex of the affected hemisphere combined with training over a period of two weeks in the subacute stage after stroke will significantly enhance cortical plasticity, functional regeneration and long-term outcome determined by clinical and functional outcome measures compared with Placebo stimulation.

Official Title
-----------------
Neuroregeneration Enhanced by TDCS in Stroke

Conditions
-----------------
Stroke

Intervention / Treatment
-----------------
* Device: DC-Stimulator to apply tDCS
* Device: DC-Stimulator to apply Sham tDCS


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Subacute stroke patients (5-45 days after stroke) with thromboembolic non-hemorrhagic subcortical or cortical, first clinically overt stroke will be included. Moderate to moderately severe upper-extremity hemiparesis, defined as an Upper Extremity Fugl-Meyer score (UEFMA) between 20 and 58 (inclusive). Exclusion Criteria: pre-existing large lesions (> 1.5 cm maximum diameter) in a brain area that belongs to the anatomically established sensorimotor/premotor system progressive stroke completely lesioned hand knob area of M1 affected if no motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) are present bilateral motor impairment florid alcohol and/or drug abuse florid severe psychiatric illness (e.g. schizophrenia) severe language disturbances that prevents the patient to give informed consent or inhibit adequate scoring because of insufficient understanding of scoring introductions tumor diseases with a life expectancy less than one year increased intracranial pressure polyneuropathy and/or ischemic peripheral disease if the sensorimotor functions of the upper extremities are affected clinically relevant severe cognitive deficits (MMSE ≤ 23) pregnancy contraindication for MRI or TMS

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
No

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Anodal tDCS<br>Direct Current (DC)-Stimulator to apply tDCS + Training | Device: DC-Stimulator to apply tDCS<br>* Anodal tDCS (20 minutes) stimulation will be applied once a day in combination with standardized upper extremity rehabilitative training<br>|
| Sham Comparator: Sham tDCS<br>Direct Current (DC)-Stimulator to apply Sham tDCS (Placebo) + Training | Device: DC-Stimulator to apply Sham tDCS<br>* Sham stimulation will be applied once a day in combination with standardized upper extremity rehabilitative training<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Upper Extremity Fugl-Meyer-Assessment (UEFMA) | standardized test of upper extremity function | 1-7 days after the end of the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Upper Extremity Fugl-Meyer-Assessment (UEFMA) | standardized test of upper extremity function | 30±10 days after the intervention | 
| Upper Extremity Fugl-Meyer-Assessment (UEFMA) | standardized test of upper extremity function | 90±20 days after the intervention | 
| Upper Extremity Fugl-Meyer-Assessment (UEFMA) | Long-term outcome | standardized test of upper extremity function | 12±1 months after the intervention | 
| Action Research Arm Test (ARAT) | standardized tests of upper extremity function | 1-7 days after the end of the intervention | 
| Action Research Arm Test (ARAT) | standardized tests of upper extremity function | 30±10 days after the intervention | 
| Action Research Arm Test (ARAT) | standardized tests of upper extremity function | 90±20 days after the intervention | 
| Action Research Arm Test (ARAT) | Long-term outcome | standardized tests of upper extremity function | 12±1 months after the intervention | 
| Nine Hole Peg Test (NHPT) | standardized test to assess fine motor skills | 1-7 days after the end of the intervention | 
| Nine Hole Peg Test (NHPT) | standardized test to assess fine motor skills | 30±10 days after the intervention | 
| Nine Hole Peg Test (NHPT) | standardized test to assess fine motor skills | 90±20 days after the intervention | 
| Nine Hole Peg Test (NHPT) | Long-term outcome | standardized test to assess fine motor skills | 12±1 months after the intervention | 
| Stroke Impact Scale (SIS) | questionnaire is to evaluate how stroke has impacted health and life of patients | 1-7 days after the end of the intervention | 
| Stroke Impact Scale (SIS) | questionnaire is to evaluate how stroke has impacted health and life of patients | 30±10 days after the intervention | 
| Stroke Impact Scale (SIS) | questionnaire is to evaluate how stroke has impacted health and life of patients | 90±20 days after the intervention | 
| Stroke Impact Scale (SIS) | Long-term outcome | questionnaire is to evaluate how stroke has impacted health and life of patients | 12±1 months after the intervention | 
| Box-and-Block Test | standardized test to assess fine motor skills | 1-7 days after the end of the intervention | 
| Box-and-Block Test | standardized test to assess fine motor skills | 30±10 days after the intervention | 
| Box-and-Block Test | standardized test to assess fine motor skills | 90±20 days after the intervention | 
| Box-and-Block Test | standardized test to assess fine motor skills | 12±1 months after the intervention | 
| Grip Force | dynamometer-based test to assess grip strength | 1-7 days after the end of the intervention | 
| Grip Force | dynamometer-based test to assess grip strength | 30±10 days after the intervention | 
| Grip Force | dynamometer-based test to assess grip strength | 90±20 days after the intervention | 
| Grip Force | dynamometer-based test to assess grip strength | 12±1 months after the intervention | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
stroke, non-invasive cortical stimulation, motor recovery, cortical plasticity, TDCS