Repetitive Transcranial Magnetic Stimulation and Multi-modality Aphasia Therapy for Post-stroke Non-fluent Aphasia

Study Overview
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Brief Summary
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Many stroke survivors experience aphasia, a loss or impairment of language affecting the production or understanding of speech. One common type of aphasia is known as non-fluent aphasia. Patients with non-fluent aphasia have difficulty formulating grammatical sentences, often producing short word fragments despite having a good understanding of what others are trying to communicate to them. Speech language pathologists (SLPs) play a central role rehabilitating persons with aphasia and administer therapy in an attempt to improve communication skills. Despite standard therapy, approximately 50% of individuals who experience aphasia acutely continue to have language deficits more than 6 months post-stroke. In most people, Broca's area is dominant in the left side of the brain. Following a left-sided stroke, the right-sided homologue of Broca's area (the pars triangularis), may adopt language function. Unfortunately, reorganizing language to the right side of the brain seems to be less effective than restoring function to the left hemisphere. Repetitive transcranial magnetic stimulation (rTMS), a form of non-invasive brain stimulation, can be used to suppress activity of specific regions in the right side of the brain to promote recovery of function in the perilesional area. Despite preliminary success in existing studies using rTMS in post-stroke aphasia, there is much work to be done to better understand the mechanisms underlying recovery. Responses to rTMS have been positive, yet heterogenous, which may be related to timing of treatments following stroke.

Official Title
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A Randomized Sham-Controlled Trial of Repetitive Transcranial Magnetic Stimulation (rTMS) and Multi-Modal Aphasia Treatment (M-MAT) for Post-Stroke Non-Fluent Aphasia

Conditions
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Stroke, Aphasia, Non-fluent

Intervention / Treatment
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* Device: 1Hz inhibitory rTMS
* Device: 1Hz sham rTMS
* Behavioral: Multi-Modality Aphasia Therapy (M-MAT)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Isolated left middle cerebral artery (MCA) stroke within past 6 months (sub-acute) or more than 6 months ago (chronic) Stroke type: Ischemic or hemorrhagic Non-fluent aphasia as determined by the Western Aphasia Battery (Fluency < 5) English is first or primary language Ability to follow 3-step commands Exclusion Criteria: Prior stroke to the right frontal lobe Current diagnosis of moderate to severe depression Diagnosis of any other psychiatric condition History of other neurologic disorders (e.g., epilepsy, brain tumor) Contraindication to MRI or TMS (metal in the head or any implanted electrical device) Has received intensive speech therapy within the past 6 months (>8 hours per week) Enrolled in another interventional study

Ages Eligible for Study
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Minimum Age: 18 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
Interventional Model Description: Participants are assigned to one of two groups for the duration of the study (Multi-modality aphasia therapy plus inhibitory rTMS or multi-modality aphasia therapy plus sham rTMS).
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multi-modality aphasia therapy plus 1Hz rTMS<br>Participants receive 10 days of 3.5hrs of multi-modality aphasia therapy (M-MAT) preceded by 20 minutes of 1Hz rTMS delivered at 100% of resting motor threshold over the right pars triangularis. | Device: 1Hz inhibitory rTMS<br>* 20 minutes of 1Hz (1200 pulses) repetitive transcranial magnetic stimulation (rTMS) applied by Magstim Rapid 2 stimulator equipped with an airfilm figure-8 coil<br>Behavioral: Multi-Modality Aphasia Therapy (M-MAT)<br>* Participants receive 3.5 hours of intensive speech therapy in small groups delivered by a blinded speech language pathologist and therapy assistant. The objective of M-MAT is to improve word production through shaping of responses (ie. Gradually increasing complexity of spoken targets towards eventual mastery) and social-mediated repetitive practice. Therapists use game-based interactive tasks and rich multi-modal cueing (gestures, written words, drawing, reading words) to improve spoken production and oral communication.<br>|
| Sham Comparator: Multi-modality aphasia therapy plus sham rTMS<br>Participants receive 10 days of 3.5hrs of multi-modality aphasia therapy (M-MAT) preceded by 20 minutes of sham rTMS is achieved using a sham TMS coil which attenuates the magnetic output of the stimulator by 80%. | Device: 1Hz sham rTMS<br>* 20 minutes of 1Hz (1200 pulses) repetitive transcranial magnetic stimulation (rTMS) applied by Magstim Rapid 2 stimulator equipped with an airfilm figure-8 sham coil.<br>Behavioral: Multi-Modality Aphasia Therapy (M-MAT)<br>* Participants receive 3.5 hours of intensive speech therapy in small groups delivered by a blinded speech language pathologist and therapy assistant. The objective of M-MAT is to improve word production through shaping of responses (ie. Gradually increasing complexity of spoken targets towards eventual mastery) and social-mediated repetitive practice. Therapists use game-based interactive tasks and rich multi-modal cueing (gestures, written words, drawing, reading words) to improve spoken production and oral communication.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline on the Western Aphasia Battery (Revised) Aphasia Quotient within one week of intervention completion | Western Aphasia Battery Aphasia quotient (WAB-AQ) composite score, composed of fluency, spontaneous speech, naming, and comprehension sub-tests. Scores range from 0 to 100, with higher scores indicating better overall speech and language abilities. Positive change from baseline indicates better outcome. | Baseline, within 1 week of completing the 10 day intervention | 
| Change from baseline on the Western Aphasia Battery (Revised) Aphasia Quotient at 3 months | Western Aphasia Battery Aphasia quotient (WAB-AQ) composite score, composed of fluency, spontaneous speech, naming, and comprehension sub-tests. Scores range from 0 to 100, with higher scores indicating better overall speech and language abilities. Positive change from baseline indicates better outcome. | Baseline and 3-month follow-up | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Trained and Untrained Picture Naming | Number of correctly named pictures from a set of trained nouns, trained verbs, untrained nouns, and untrained verbs. | Baseline, within 1 week of completing the 10 day intervention and 3-month follow-up | 
| Scenario Test (UK) | Test of functional communication based on everyday conversational scenarios | Baseline, within 1 week of completing the 10 day intervention and 3-month follow-up | 
| Connected speech sample | Records the number of correct information units provided by participants while re-telling a familiar story (e.g., the three little pigs) | Baseline, within 1 week of completing the 10 day intervention and 3-month follow-up | 
| Cognitive Linguistic Quick Test - aphasia administration | Brief assessment of non-verbal cognition | Baseline | 
| Overt Naming Functional Magnetic Resonance Imaging | Functional neuroimaging collected during picture naming task to assess activity associated with naming | Baseline, within 1 week of completing the 10 day intervention and 3-month follow-up | 
| Resting-state Functional Magnetic Resonance Imaging | Functional neuroimaging collected during rest to be used for functional connectivity | Baseline, within 1 week of completing the 10 day intervention and 3-month follow-up | 
| Magnetic Resonance Spectroscopy | 1H proton spectroscopy used to measure metabolite concentrations within the right inferior frontal gyrus | Baseline, within 1 week of completing the 10 day intervention and 3-month follow-up | 
| Diffusion weighted Magnetic Resonance Imaging | Neuroimaging measuring the diffusion of water to be used for white matter reconstruction | Baseline, within 1 week of completing the 10 day intervention and 3-month follow-up | 
| Communication Effectiveness Index | Caregiver completed questionnaire to assess functional communication | Baseline, within 1 week of completing the 10 day intervention and 3-month follow-up | 
| Stroke Aphasic Depression Questionnaire (SADQ) | A 10-item questionnaire completed by a caregiver to quickly assess depressive symptoms in stroke patients with aphasia. | Baseline, within 1 week of completing the 10 day intervention and 3-month follow-up | 
| Stroke and Aphasia Quality of Life Scale (SAQOL) | Assesses mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The EQ also records the patient's self-rated health on a vertical visual analogue scale. This can be used as a quantitative measure of health outcome that reflects the patient's own judgement. | Baseline, within 1 week of completing the 10 day intervention and 3-month follow-up | 
| Western Aphasia Battery - Bedside (WAB) | Assesses the linguistic skills and main nonlinguistic skills of adults with aphasia. This provides information for the diagnosis of the type of aphasia. | Screening appointment | 
| Apraxia Battery for Adults (ABA) | Assesses characteristics of verbal apraxia | Screening appointment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Non-invasive brain stimulation, Transcranial Magnetic Stimulation, Multi-modality aphasia therapy, Neuroimaging