rTMS and Multi-Modality Aphasia Therapy for Post-Stroke 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 Pilot Trial of Repetitive Transcranial Magnetic Stimulation (rTMS) and Multi-Modality 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
* Behavioral: Multi-Modality Aphasia Therapy (M-MAT)
* Device: 1Hz sham rTMS


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Isolated left middle cerebral artery (MCA) stroke more than 6 months ago (chronic) Stroke type: Ischemic or hemorrhagic Non-fluent aphasia as determined by the Western Aphasia Battery (Fluency < 5) Right-hand dominant prior to stroke 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
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Multi-modality aphasia therapy plus 1Hz rTMS<br>Chronic stroke patients, 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>Chronic stroke patients, 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%. | 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>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>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline on the Boston Naming Test within one week of intervention completion | Number of spontaneously produced correct responses to a series of line drawings. That is, the number of correctly named images. | Baseline, within 1 week of completing the 10 day intervention | 
| Change from baseline on the Boston Naming Test at 3 months | Number of spontaneously produced correct responses to a series of line drawings. That is, the number of correctly named images. | 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 | 
| Story Narrative Task | Retelling of the Cinderella task as a measure of discourse, performance is quantified by number of correct information units. | Baseline, within 1 week of completing the 10 day intervention and 3-month follow-up | 
| Patient Health Questionnaire (PHQ-9) | A 9-item questionnaire completed by a caregiver to quickly assess depressive symptoms. The scale ranges from 0 to 27 with higher scores indicating greater endorsement of depressive symptoms. | Baseline, within 1 week of completing the 10 day intervention and 3-month follow-up | 
| EuroQoL-5D-5L | Assesses mobility, self-care, usual activities, pain/discomfort and anxiety/depression. The answers given can be converted into EQ-5D index with scores anchored at 0 for death and 1 for perfect health. The EQ-5D also records the patient's self-rated health on a vertical visual analogue scale ranging from 0 to 100 with higher scores indicating higher self-perceived quality of life. 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 | 

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