TMS in Aphasia Recovery

A Blinded Randomized Sham-Controlled Incomplete Crossover Trial of Low-Frequency Contralesional Repetitive Transcranial Magnetic Stimulation in the Treatment of Aphasia in Patients With Chronic Stroke

Stroke often causes substantial problems in speaking or understanding speech. Treatments for these problems are currently very limited. Limited studies to date suggest that repetitive Transcranial Magnetic Stimulation (TMS) to the side of the brain opposite to the side on which the stroke occurred may improve language function. The investigators are testing this hypothesis by giving daily 20 minute sessions of repeated TMS to the right (unaffected) side of the brain; the investigators test language function with a variety of tests both before and after the treatment with TMS and subjects are required to undergo functional MRI scans before and after treatment. TMS is a procedure in which a coil is placed next to the head of the subject and an electrical current passes through the coil causing a magnetic field that, in turn, causes a small electric current in the portion of the brain underneath the coil.

Study Overview

• Status: Completed
• Conditions: Aphasia
• Intervention / Treatment: Device: Sham TMS; Device: Repetitive Transcranial Magnetic Stimulation

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • University of Pennsylvania

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Aphasic patients will have had single, unilateral left hemisphere ischemic stroke, which spared the supplementary motor area (SMA)
• With the exception of lacunar infarcts less than ≤ 1.5 cm (as measured by neuroimaging), the stroke causing the patients' impairments must be the only stroke.
• Aphasic patients will be at least 6 months post-stroke and have mild-severe, non-fluent speech
• Participants must be able to understand the nature of the study, and give informed consent

Exclusion Criteria:

• Patients with more than one stroke
• Primary hemorrhagic stroke. Note: It is recognized that some ischemic strokes may have a minor amount of hemosiderin in the parenchyma. If this occurs, this is not considered a "hemorrhagic stroke" referred to in this exclusion criterion.
• Intracranial metallic bodies from prior neurosurgical procedure
• Signs of increased intracranial pressure as assessed by ophthalmic exam and patient symptoms
• Implanted pacemaker, medication pump, vagal nerve stimulator, deep brain stimulator, TENS unit or ventriculoperitoneal shunt
• History of seizure or unexplained loss of consciousness during the year prior to the initiation of the study
• Pregnancy. If the patient cannot rule out pregnancy then a pregnancy test will be conducted prior to inclusion into the study
• Family history of epilepsy
• Acute, unstable medical conditions
• History of substance abuse within the last 6 months
• Abnormal neurologic exam other than as signs of the condition studied in the present protocol
• History of known structural brain abnormality other than as signs of the condition studied in the present protocol
• History of tinnitus
• History of bipolar disorder
• Consumption of medicines known to lower the seizure threshold
• History of head injury with unconsciousness lasting more than 5 minutes
• Previous brain surgery
• Other medical or neurologic conditions, aside from stroke, in which the likelihood of developing a seizure is known to be increased
• Other medical or neurologic conditions, in which a seizure would be particularly harmful
• Significant cardiac disease
• Intracardiac lines of any type
• Current serious or unstable medical illness, including renal, hepatic, cardiovascular, gastrointestinal, endocrinologic, neurologic, immunologic, or hematological disease, that could require admission to a hospital within 3 months, or that death is anticipated within 3 years, or that requires daily supervision by a health professional
• Administration of any investigational drug within 5 half-lives of the drug prior to testing

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: DOUBLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
ACTIVE_COMPARATOR: Active TMS; There are 10 TMS sessions over 2 consecutive weeks in which 20 minutes (1200 pulses) of 1 Hz active TMS are delivered to a previously determined optimal response site in right frontal lobe.	Device: Repetitive Transcranial Magnetic Stimulation; Active TMS will be at 90% motor threshold
SHAM_COMPARATOR: Sham TMS; There are 10 TMS sessions over 2 consecutive weeks in which 20 minutes (1200 pulses) of 1 Hz TMS are delivered, however, the coil will be rotated 90 degrees during stimulation.	Device: Sham TMS; Sham TMS will be administered

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Boston Naming Test	The Boston Naming Test is an assessment of confrontation naming, where a score ranges from 0 (no items named correctly) to 36 (all items named correctly)	Baseline, 2 months and 6-months after the last rTMS treatment session

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Picture Description of the Boston Diagnostic Aphasia Exam	The picture description of the Boston Diagnostic Aphasia Exam is a measurement of spontaneous speech, elicited by a picture description. It is not a scale. Quantitative Production Analysis (QPA) is used to analyze the production of words related to the picture stimulus. Total number of Narrative Words produced, defined as total words minus stereotyped utterances, task-related comments, or comments cued by administrator, was determined using QPA as a measure of discourse productivity.	Baseline and 2 months after the last rTMS treatment session
Boston Diagnostic Aphasia Exam - Word Discrimination Subtest	The Boston Diagnostic Aphasia Exam - Word Discrimination Subtest is an assessment of auditory comprehension via word discrimination, where a score ranges from 0 (no items correct) to 72 (all items correct)	Baseline and 2 months after the last rTMS treatment session
Boston Diagnostic Aphasia Examination - Commands Subtest	The Boston Diagnostic Aphasia Examination - Commands Subtest is an assessment of auditory comprehension via command following, where a score ranges from 0 (no items correctly performed) to 15 (all items correctly performed). Percent change was calculated by taking the mean performance at 2-months after rTMS treatment and subtracting mean performance at baseline, then dividing by the mean baseline performance and multiplying by 100.	Baseline and 2 months after the last rTMS treatment

Collaborators and Investigators

• Sponsor: University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 26, 2007
• Primary Completion (ACTUAL): August 30, 2011
• Study Completion (ACTUAL): August 30, 2011

Study Registration Dates

• First Submitted: February 2, 2021
• First Submitted That Met QC Criteria: February 25, 2021
• First Posted (ACTUAL): March 2, 2021

Study Record Updates

• Last Update Posted (ACTUAL): November 26, 2021
• Last Update Submitted That Met QC Criteria: October 27, 2021
• Last Verified: April 1, 2021

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Language Disorders; Communication Disorders; Speech Disorders; Aphasia
• Other Study ID Numbers: 805362

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

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