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

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

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.

Study Overview

• Status: Completed
• Conditions: Stroke; Aphasia, Non-fluent
• Intervention / Treatment: Device: 1Hz inhibitory rTMS; Behavioral: Multi-Modality Aphasia Therapy (M-MAT); Device: 1Hz sham rTMS

• Study Type: Interventional
• Enrollment (Actual): 46
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Alberta
    • Calgary, Alberta, Canada, T2N 2T9
      • Foothills Medical Centre

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Multi-modality aphasia therapy plus 1Hz rTMS; 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; 20 minutes of 1Hz (1200 pulses) repetitive transcranial magnetic stimulation (rTMS) applied by Magstim Rapid 2 stimulator equipped with an airfilm figure-8 coil; Behavioral: Multi-Modality Aphasia Therapy (M-MAT); 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.
Sham Comparator: Multi-modality aphasia therapy plus sham rTMS; 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%.	Behavioral: Multi-Modality Aphasia Therapy (M-MAT); 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.; Device: 1Hz sham rTMS; 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.

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Calgary
• Investigators: Principal Investigator: Sean P Dukelow, MD PhD FRCPC, University Of Calgary

Study record dates

Study Major Dates

• Study Start (Actual): April 15, 2021
• Primary Completion (Actual): August 21, 2023
• Study Completion (Actual): August 24, 2023

Study Registration Dates

• First Submitted: September 20, 2019
• First Submitted That Met QC Criteria: September 23, 2019
• First Posted (Actual): September 25, 2019

Study Record Updates

• Last Update Posted (Actual): August 12, 2024
• Last Update Submitted That Met QC Criteria: August 9, 2024
• Last Verified: August 1, 2024

More Information

Terms related to this study

• Keywords: Transcranial Magnetic Stimulation; Neuroimaging; Non-invasive brain stimulation; Multi-modality aphasia therapy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Language Disorders; Communication Disorders; Speech Disorders; Stroke; Aphasia; Aphasia, Broca
• Other Study ID Numbers: REB19-0829

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No plan to make IPD available to other researchers

Drug and device information, study documents

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