Transcranial Magnetic Stimulation + Language Therapy to Treat Mild Aphasia (TMS)

Personalized Transcranial Magnetic Stimulation and Constraint Induced Language Therapy to Treat Mild Post-Stroke Aphasia

The goal of this clinical trial is to determine if Transcranial Magnetic Stimulation (TMS) combined with Speech-Language Therapy (SLT) is an effective treatment for mild aphasia in persons with chronic stroke.

The main questions this study aims to answer are:

1. Can TMS combined with SLT improve conversational speech and comprehension?
2. Can we identify specific behavioral and biological characteristics that would benefit most from the TMS and SLT treatment?

Researchers will compare real TMS to sham (fake) TMS to see whether TMS can treat post-stroke mild aphasia.

Participants will:

• Complete a screening and medical intake to determine eligibility
• Undergo a MRI
• Participate in 10 consecutive sessions (Monday-Friday) of TMS and SLT treatment
• Complete follow-up assessments 2 and 4 months after treatment

Study Overview

• Status: Recruiting
• Conditions: Stroke; Aphasia; Aphasia, Acquired; Aphasia Following Cerebral Infarction
• Intervention / Treatment: Device: Transcranial Magnetic Stimulation (TMS); Behavioral: Speech-Language Therapy (SLT)

Detailed Description

Aphasia is an acquired disorder of language that occurs in approximately 30% of individuals with stroke and impacts approximately 1 million Americans (see NINDS.NIH.gov). Current treatments for aphasia are only modestly beneficial, so there is a clear need for more efficacious therapy.

Previous research has demonstrated that TMS improves language performance in persons with aphasia and the benefit has been shown to be sustained. All studies of which we are aware, however, have included participants with moderate/severe aphasia. The issue of mild aphasia has received little attention to date but as there is an increasing recognition that even very mild language deficits have important negative consequences for employment and social well-being. This study will aim to treat mild aphasia with TMS and SLT emphasizing conversations speech.

One limitation of TMS has been variability in response; TMS has shown good within-subject reliability but more substantial variability between subjects. In recognition of these issues, "electrical field" (e-field) models have been developed to account for these individual differences in anatomy. We will the utilize e-field models in conjunction with an individually determined resting motor threshold to generate a personalized treatment regimen that is likely to ensure that all subjects receive the same TMS intensity relative to their individual motor threshold and greatly reduces the possibility of under- or over-dosing with respect to TMS intensity. We will employ continuous theta-burst stimulation, 600 brief electrical pulses delivered in 40 seconds, over the right front part of the brain (pars triangularis).

Participants who are enrolled can expect to undergo a battery of tests to define their language function as well as a research MRI scan that will be used to guide TMS therapy and to assess the size and location of the stroke and its impact on brain pathways. After baseline testing, subjects will undergo treatment using TMS (or sham) + SLT for 10 sessions (Monday-Friday) over the course of 2 consecutives week. Follow-up assessment of language functioning will be assessed immediately, 2 months and 4 months after treatment.

Participants will be compensated for their time and travel.

• Study Type: Interventional
• Enrollment (Estimated): 24
• Phase: Phase 2

Contacts and Locations

• Study Contact: Name: Harris Drachman, MS; Phone Number: 215-964-2502; Email: harris.drachman@pennmedicine.upenn.edu
• Study Contact Backup: Name: Daniela Sacchetti, MS; Email: danielas@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19014
      • Recruiting
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Left Hemisphere stroke
• Stroke occurred more than 6 months ago
• Mild Aphasia (WAB AQ score > 85)
• Proficient in English

Exclusion Criteria:

• Ongoing substance or alcohol abuse
• Other neurological disorders, beside stroke (i.e. dementia, traumatic brain injury, multiple sclerosis)
• Active psychiatric disorders (i.e. bipolar disorder, schizophrenia)
• Pacemaker or cardiac defibrillator
• Diagnosis of tinnitus
• Epilepsy, or seizure in the past 6 months

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Real TMS; Some of our participants will be randomized to the real treatment arm where they will receive 10 sessions of real TMS paired with speech-language therapy.	Device: Transcranial Magnetic Stimulation (TMS); TMS, is a form of non-invasive brain stimulation, that uses magnetic pulses to stimulate specific areas of the brain. In this study we will utilize theta-burst stimulation which uses a higher frequency pulse of 50 Hz delivered for 40 seconds for a total of 600 pulses.; Behavioral: Speech-Language Therapy (SLT); Our SLT protocol draws from two theories and evidence-based cognitive-linguistic frameworks: (1) conversational alignment, which engages priming of lexical and syntactic structures through dialogue and conversation and (2) increased tolerance of memory load in the context of sentence repetition and dialogue tasks. Administration of these tasks will abide by principles of constraint-induced language therapy, i.e., intense treatment schedule and verbal responding only. All participants will receive SLT.
Sham Comparator: Fake TMS; Some of our participants will be randomized to the sham treatment arm where they will receive 10 sessions of fake TMS paired with speech-language therapy.	Behavioral: Speech-Language Therapy (SLT); Our SLT protocol draws from two theories and evidence-based cognitive-linguistic frameworks: (1) conversational alignment, which engages priming of lexical and syntactic structures through dialogue and conversation and (2) increased tolerance of memory load in the context of sentence repetition and dialogue tasks. Administration of these tasks will abide by principles of constraint-induced language therapy, i.e., intense treatment schedule and verbal responding only. All participants will receive SLT.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Sentence Processing	Change in performance on the Temple Assessment of Language and Short-term Memory in Aphasia (TALSA) sentence processing composite score.	From baseline to 4 months post-intervention

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Semantic and Phonological Processing	Change in performance on the TALSA composite semantic processing score and phonological processing score.	From baseline to 4 months post-intervention
Elicited Speech	Change in performance on the Nicholas & Brookshire picture description and Story Retell scores.	From baseline to 4 months post-intervention

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Collaborators: Temple University; National Institute on Deafness and Other Communication Disorders (NIDCD)
• Investigators: Principal Investigator: H. Branch Coslett, MD, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): February 11, 2025
• Primary Completion (Estimated): August 31, 2026
• Study Completion (Estimated): August 31, 2026

Study Registration Dates

• First Submitted: February 18, 2025
• First Submitted That Met QC Criteria: February 18, 2025
• First Posted (Actual): February 24, 2025

Study Record Updates

• Last Update Posted (Actual): March 5, 2026
• Last Update Submitted That Met QC Criteria: March 4, 2026
• Last Verified: March 1, 2026

More Information

Terms related to this study

• Keywords: stroke; Transcranial Magnetic Stimulation; aphasia; non-invasive brain stimulation
• Additional Relevant MeSH Terms: Neurologic Manifestations; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Neurobehavioral Manifestations; Communication Disorders; Language Disorders; Speech Disorders; Pathological Conditions, Signs and Symptoms; Signs and Symptoms; Stroke; Aphasia; Therapeutics; Patient Care; Rehabilitation; Aftercare; Continuity of Patient Care; Magnetic Field Therapy; Rehabilitation of Speech and Language Disorders; Transcranial Magnetic Stimulation; Speech Therapy
• Other Study ID Numbers: 857363; 1R21DC021833-01 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: No, the study team does not plan to share participating data at this time.

Drug and device information, study documents

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