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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active TMS | Active Comparator | 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. |
|
| Sham TMS | Sham Comparator | 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. |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Repetitive Transcranial Magnetic Stimulation | Device | Active TMS will be at 90% motor threshold |
|
| 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 |
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| 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. |
Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| H. Branch Coslett, MD | University of Pennsylvania | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University of Pennsylvania | Philadelphia | Pennsylvania | 19104 | United States |
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Patients were assessed against the study inclusion and exclusion criteria. Eligible patients then underwent language tests before and after 6 ten minute sessions of rTMS to determine if there was a right hemisphere cortical region which, when suppressed with 1 Hz rTMS, resulted in significantly improved naming. If no benefit was observed from stimulation, the patient did not continue on to the treatment phase.
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| ID | Title | Description |
|---|---|---|
| FG000 | 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. Repetitive Transcranial Magnetic Stimulation: Active TMS will be at 90% motor threshold |
| FG001 | 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. Sham TMS: Sham TMS will be administered at least 2 months later, patients then receive Active TMS if they so choose. 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. Repetitive Transcranial Magnetic Stimulation: Active TMS will be at 90% motor threshold |
| Title | Milestones | Reasons Not Completed | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Initial Randomization |
| |||||||||||||
| Sham Crossover to Active TMS Arm |
|
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| ID | Title | Description |
|---|---|---|
| BG000 | 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. Repetitive Transcranial Magnetic Stimulation: Active TMS will be at 90% motor threshold |
| BG001 |
| Units | Counts |
|---|---|
| Participants |
|
| Title | Description | Population Description | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Denominator Units Selected | Denominators | Classes |
|---|---|---|---|---|---|---|---|---|---|
| Age, Continuous | Mean |
| Type | Title | Description | Population Description | Reporting Status | Anticipated Posting Date | Parameter Type | Dispersion Type | Unit of Measure | Calculate Percentage | Time Frame | Units Analyzed | Denominator Units Selected | Arm/Group Information | Denominators | Classes | Analyses | |||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Primary | 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) | 9 participants completed the Active TMS arm and were available for follow-up at 2- and 6- months post treatment. | Posted | Mean | Standard Deviation | percent change from baseline | Baseline, 2 months and 6-months after the last rTMS treatment session |
|
Adverse event data was collected from enrollment in the study to 30 days following administration of rTMS treatment, on average 303.3 days.
An adverse event is any symptom, sign, illness or experience that develops or worsens in severity during the course of the study. A serious adverse event is any AE that is: fatal, life-threatening, requires or prolongs hospital stay, results in persistent or significant disability or incapacity, a congenital anomaly or birth defect, an important medical event Important medical events are those that may not be immediately life threatening, but are clearly of major clinical significance.
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| ID | Title | Description | Deaths (Affected) | Deaths (At Risk) | Serious Events (Affected) | Serious Events (At Risk) | Other Events (Affected) | Other Events (At Risk) |
|---|---|---|---|---|---|---|---|---|
| EG000 | 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. Repetitive Transcranial Magnetic Stimulation: Active TMS will be at 90% motor threshold |
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| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Samuel Cason | University of Pennsylvania | 215-573-4336 | sacason@pennmedicine.upenn.edu |
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| ID | Term |
|---|---|
| D001037 | Aphasia |
| ID | Term |
|---|---|
| D013064 | Speech Disorders |
| D007806 | Language Disorders |
| D003147 | Communication Disorders |
| D019954 | Neurobehavioral Manifestations |
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| ID | Term |
|---|---|
| D050781 | Transcranial Magnetic Stimulation |
| ID | Term |
|---|---|
| D055909 | Magnetic Field Therapy |
| D013812 | Therapeutics |
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The study involves two arms. The study involves a sham treatment control for half of the patients; all patients randomized to the sham treatment will be enrolled in the treatment phase after completing the sham treatment. Patients will be randomly assigned to the treatment arm or the sham treatment arm of the study. There are 3 phases: a pre-treatment evaluation phase in which baseline language and imaging data are obtained and the optimal site for stimulation is determined; a treatment phase during which TMS is delivered on 10 occasions; and a post-treatment phase during which effects of the treatment will be assessed using behavioral measures as well as fMRI at 2 and 6-months. Participants in the sham arm will undergo the same behavioral testing, MRI, and fMRI that will be administered in the treatment protocol. After the 2-month follow up visit, patients in the sham arm will be told that they did not receive real TMS and will be offered the opportunity to enter the treatment arm.
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The procedure for localizing the site of stimulation and TMS administration will be identical to the treatment arm, except the coil will be rotated 90 degrees during the process/administration.
| Sham TMS | Device | Sham TMS will be administered |
|
| 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 |
| NOT COMPLETED |
|
| 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. Sham TMS: Sham TMS will be administered |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Region of Enrollment | Number | participants |
|
| OG001 |
| Active TMS 6-month Follow-Up |
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. Repetitive Transcranial Magnetic Stimulation: Active TMS will be at 90% motor threshold Outcome measures are then assessed 6 months after TMS treatment sessions. |
|
|
| Other Pre-specified | 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. | Comparison of total narrative word output change between baseline and 2-months between Active arm and Sham Arm. Active TMS arm includes both 5 participants initially randomized to Active TMS arm, plus 5 people who crossed over to Active arm after Sham arm. | Posted | Mean | Standard Deviation | change in number of words from baseline | Baseline and 2 months after the last rTMS treatment session |
|
|
|
| Other Pre-specified | 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) | Comparison of percent change in outcome between baseline and 2-months between Active arm and Sham Arm. Active TMS arm includes both 5 participants initially randomized to Active TMS arm, plus 5 people who crossed over to Active arm after Sham arm. | Posted | Mean | Standard Deviation | Percent change from baseline | Baseline and 2 months after the last rTMS treatment session |
|
|
|
| Other Pre-specified | 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. | Comparison of percent change in outcome between baseline and 2-months between Active arm and Sham Arm. Active TMS arm includes both 5 participants initially randomized to Active TMS arm, plus 5 people who crossed over to Active arm after Sham arm. | Posted | Mean | Standard Deviation | percent change from baseline | Baseline and 2 months after the last rTMS treatment |
|
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|
| 0 |
| 10 |
| 0 |
| 10 |
| 0 |
| 10 |
| EG001 | 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. Sham TMS: Sham TMS will be administered | 0 | 5 | 0 | 5 | 0 | 5 |
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| D009461 | Neurologic Manifestations |
| D009422 | Nervous System Diseases |
| D012816 | Signs and Symptoms |
| D013568 | Pathological Conditions, Signs and Symptoms |