Transcranial Direct Current Stimulation to Enhance Training Effectiveness in Chronic Post-Stroke Aphasia

Study Overview
=================
Brief Summary
-----------------
The aim of the study is to investigate whether intensive speech-language therapy (SLT) combined with anodal transcranial direct current stimulation (tDCS) leads to better communication performance than SLT combined with placebo stimulation (using sham-tDCS).

Detailed Description
-----------------
Intensive speech-language therapy (SLT) can promote recovery from chronic post-stroke aphasia, but effect sizes are moderate. This highlights the pressing need to explore adjunct strategies, such as transcranial direct current stimulation (tDCS), to enhance training effectiveness. Recently, the investigators provided evidence from a single-center randomized controlled trial (RCT) suggesting that anodal-tDCS of the left primary motor cortex (M1) improves naming and communication ability in chronic post-stroke aphasia, with medium-to-large effect sizes. However, prior to integration into clinical routine, a multi-center RCT with adequate power, duration, and outcomes relevant to everyday life is required, which is the goal of the present study. After trial completion, a workshop with relevant stakeholders will ensure transfer into best-practice guidelines.

Official Title
-----------------
Transcranial Direct Current Stimulation to Enhance Training Effectiveness in Chronic Post-Stroke Aphasia

Conditions
-----------------
Aphasia, Post-stroke

Intervention / Treatment
-----------------
* Other: Anodal transcranial direct current stimulation (tDCS) combined with speech-language therapy (SLT, including naming therapy and communicative-pragmatic therapy)


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: left-hemisphere cortical or subcortical stroke with first-ever aphasic symptoms at least 6 months post-onset of stroke; aphasia, as determined by the Aachen Aphasia Test (AAT); 13 moderate-to-severe word finding difficulties (maximum of 75% correct items on a computerized naming task at baseline); at least 1 correct reaction on the first part of the AAT subscale Token Test (ensuring basic comprehension skills); at least 1 point on the communicative task of the AAT subscale Spontaneous Speech (ensuring basic communication abilities); German as first language; intact left-hemisphere hand knob without right prefrontal lesions for placement of tDCS electrodes, as confirmed by magnetic resonance imaging or computer tomography scans. Exclusion Criteria: contraindications for tDCS (e.g., cardiac pacemaker, history of seizures, implanted metal inside the head); more than one clinically apparent stroke with aphasic symptoms; other severe neurological diseases (e.g., brain tumor, and subdural hematoma); epilepsy with seizures during the last 12 months prior to study start and/or intake of sedating antiepileptic drugs (barbiturates and benzodiazepines), history of severe alcohol or drug abuse; current severe depression; current psychosis or other relevant psychiatric condition; very severe apraxia of speech, as revealed by Hierarchical Word Lists; severe non-verbal cognitive deficits, as indicated by the Corsi Block-Tapping Task; severe uncontrolled medical problems; severely impaired vision or hearing that prevents patients from engaging in intensive SLT; changes in centrally active drugs within 2 weeks prior to study inclusion.

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 70 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
Interventional Model Description: Two daily sessions of intensive speech-language therapy combined with transcranial direct current stimulation of the left primary motor cortex (M1)
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Experimental group<br>Anodal transcranial direct current stimulation (tDCS) combined with speech-language therapy (SLT, including naming therapy and communicative-pragmatic therapy) | Other: Anodal transcranial direct current stimulation (tDCS) combined with speech-language therapy (SLT, including naming therapy and communicative-pragmatic therapy)<br>* Two daily sessions of intensive SLT combined with tDCS of the left primary motor cortex (M1)<br>|
| Sham Comparator: Control group<br>Placebo stimulation (using sham-tDCS) combined with SLT | Other: Anodal transcranial direct current stimulation (tDCS) combined with speech-language therapy (SLT, including naming therapy and communicative-pragmatic therapy)<br>* Two daily sessions of intensive SLT combined with tDCS of the left primary motor cortex (M1)<br>|

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

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in communication ability, as assessed by the Amsterdam Nijmegen Everyday Language Test | Amsterdam Nijmegen Everyday Language Test (A-scale; parallel versions used in counterbalanced order across participants); cf. Blomert L, Kean ML, Koster C, et al. Amsterdam-Nijmegen Everyday Language Test-Construction, Reliability and Validity. Aphasiology 1994; 8: 381-407. | Before the 3-week treatment period; immediately after the 3-week treatment period; 6- and 12-month follow ups | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in naming ability, as assessed based on personally relevant trained and untrained items, consistent with previous work (see description) | Personally relevant trained and untrained items, consistent with previous work; cf. Meinzer M, Darkow R, Lindenberg R, et al. Electrical stimulation of the motor cortex enhances treatment outcome in post-stroke aphasia. Brain 2016; 139: 1152-1163. | Before the 3-week treatment period; immediately after the 3-week treatment period; 6- and 12-month follow ups | 
| Change in (non-)verbal communication, as assessed by the Scenario Test | Scenario Test; cf. Nobis-Bosch R, Abel S, Krzok F, et al. Szenario Test-Testung verbaler und nonverbaler Aspekte aphasischer Kommunikation. ProLog, in preparation. | Before the 3-week treatment period; 6-month follow-up | 
| Change in (non-)verbal communication, as assessed by the Communicative Effectiveness Index | Communicative Effectiveness Index; cf. Lomas J, Pickard L, Bester S, et al. The Communicative Effectiveness Index: development and psychometric evaluation of a functional communication measure for adult aphasia. J Speech Hear Disord 1989; 54: 113-124. | Before the 3-week treatment period; immediately after the 3-week treatment period; 6- and 12-month follow ups | 
| Change in attention and executive function, as assessed by the subscales Go/NoGo and Alertness from Test of Attentional Performance | Subscales Go/NoGo and Alertness from Test of Attentional Performance; cf. Zimmermann P and Fimm B. Testbatterie zur Aufmerksamkeitsprüfung (TAP). Herzogenrath: PSYTEST Verlag, 2002. | Before the 3-week treatment period; 6-month follow up | 
| Change in non-verbal episodic memory, as assessed by the Figure Recognition Task from Benton Visual Retention Test | Figure Recognition Task from Benton Visual Retention Test; cf. Benton Sivan A and Spreen O. Benton Test. Bern: Huber, 2009. | Before the 3-week treatment period; 6-month follow up | 
| Change in mood, as assessed by the German version of the 10-item Stroke Aphasic Depression Questionnaire | German version of the 10-item Stroke Aphasic Depression Questionnaire (SADQH-10); cf. Cobley CS, Thomas SA, Lincoln NB, et al. The assessment of low mood in stroke patients with aphasia: reliability and validity of the 10-item Hospital version of the Stroke Aphasic Depression Questionnaire (SADQH-10). Clin Rehabil 2012; 26: 372-381. | Before the 3-week treatment period; immediately after the 3-week treatment period; 6- and 12-month follow ups | 
| Change in health-related quality of life, as assessed by the Stroke and Aphasia Quality of Life Scale | Stroke and Aphasia Quality of Life Scale (SAQOL-39g); cf. Hilari K, Lamping DL, Smith SC, et al. Psychometric properties of the Stroke and Aphasia Quality of Life Scale (SAQOL-39) in a generic stroke population. Clin Rehabil 2009; 23: 544-557. | Before the 3-week treatment period; immediately after the 3-week treatment period; 6- and 12-month follow ups | 
| Change in health-related quality of life, as assessed by the EuroQol Health-Related Quality of Life Questionnaire | EuroQol Health-Related Quality of Life Questionnaire (EQ-5D-5L); cf. EuroQol G. EuroQol-a new facility for the measurement of health-related quality of life. Health Policy 1990; 16: 199-208. | Before the 3-week treatment period; immediately after the 3-week treatment period; 6- and 12-month follow ups | 
| Change in direct and indirect costs during the 12-month study period, as assessed by the self-developed Patient Resource Consumption Questionnaire | Direct and indirect costs during the 12-month study period, as determined by the self-developed Patient Resource Consumption Questionnaire considering common standardized unit cost assumptions. | Before the 3-week treatment period; 6- and 12-month follow ups | 
| Change in direct and indirect costs during the 12-month study period, as assessed by the Quality-Adjusted Life Years | Quality-Adjusted Life Years; cf. Whitehead SJ and Ali S. Health outcomes in economic evaluation: the QALY and utilities. Br Med Bull 2010; 96: 5-21. | Before the 3-week treatment period; 6- and 12-month follow ups | 
| Change in unpaid support provided by family members or friends, as assessed by the Burden of informal caregivers | Burden of informal caregivers; cf. van Exel NJ, Koopmanschap MA, van den Berg B, et al. Burden of informal caregiving for stroke patients. Identification of caregivers at risk of adverse health effects. Cerebrovasc Dis 2005; 19: 11-17. | Before the 3-week treatment period; immediately after the 3-week treatment period; 6- and 12-month follow ups | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Rehabilitation, Intensive speech-language therapy, Transcranial direct current stimulation