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| ID | Type | Description | Link |
|---|---|---|---|
| R01DC016800-01A1 | U.S. NIH Grant/Contract | View source |
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| Name | Class |
|---|---|
| National Institutes of Health (NIH) | NIH |
| National Institute on Deafness and Other Communication Disorders (NIDCD) | NIH |
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Impaired verbal communication is a cardinal symptom of Alzheimer Disease (AD) and the source of enormous distress and disability. Effective therapies for this deficit are lacking. In light of the emerging literature demonstrating that Transcranial Magnetic Stimulation (TMS) improves general cognition in subjects with Alzheimer Disease (AD), the investigators propose to study the effectiveness of TMS as a therapy for impaired verbal communication. The hypothesis to be tested is that TMS combined with Constraint Induced Language Therapy (CILT) improves verbal communication more than sham TMS and CILT. A second aim is to use state-of-the-art neuroimaging to understand the mechanisms underlying any beneficial effect of the treatment.
TMS is a technique by which a brief electrical current is induced in brain tissue causing a brief suppression of the excitability of the underlying tissue; the technique, which was introduced in the 1980s and has been extensively used around the world, has been shown to transiently improve or disrupt specific cognitive operations. To achieve this end, a coil is positioned against the subject's head. The delivery of a single pulse begins with the discharge of current from a capacitor into a circular or figure-of-eight coil; this electrical current generates a brief magnetic field of up to 2.2 Tesla. As the pulse of electricity has a rise time of 0.2 ms. and a duration of 1 ms., the magnetic field changes in intensity quite rapidly. Because the magnetic field passes freely through the scalp, skull, and meninges, the flux in the magnetic field induces a small electric field in the brain that transiently alters neural activity.
TMS may be delivered in a variety of ways. The investigators propose to use 10 Hz TMS; that is, TMS pulses will be delivered at a frequency of 10/second, for a total of 1200 pulses. Using the figure-of-eight coil to be employed here, TMS is thought to affect activity in approximately 1 cubic cm. of cortex. Many investigators have employed TMS for AD with a frequency of 10 Hz and most have delivered 1200 pulses per session.
The baseline phase will consist of 3 sessions, each lasting 1-2 hours depending on the stamina of the subject. The point of the baseline testing is to characterize the subject's language function. To that end, a number of standard language and neuropsychological tasks will be administered. These include the Western Aphasia Battery, Pyramids and Palm Trees test, Figural Fluency Test, word and non-word repetition tasks, spontaneous narrative production, CILT stimulus naming, and the Repeatable Battery for the Assessment of Neuropsychological Status. Additionally, during the baseline, subjects will undergo MRI of the brain or, if they have a contraindication to MRI, a CAT scan of the head. No contrast will be used.
In the treatment phase, there will be 10 TMS sessions over 2 consecutive weeks in which 30 two-second stimulation trains of 10 Hz TMS will be delivered every 30 seconds to the left inferior pars triangularis and to the left posterior superior left temporal gyrus at 100% motor threshold. There will be a total of 600 pulses to each site in each session for a total of 1200 pulses per session. Each TMS treatment session will be immediately followed by a 60-90 minute session of CILT.
There will be two 3-month post-treatment visits and two 6-month post-treatment visits in which the full battery of language and cognitive assessments will be repeated. Subjects who are able to undergo MRI scanning will have anatomic and fMRI scans at the first 6-month post-treatment visit.
The investigators will pair TMS with CILT which has been shown to have positive outcomes in post-stroke aphasia. CILT invokes use-dependent learning in communicative interactions by requiring spoken output and restricting use of alternative forms of communication, such as gestures. The investigators will use a dual card-matching task modeled after Maher et al. As in the original CILT design, the participant interacts verbally with a conversational partner (here, the speech language pathologist), in turn requesting a card of given description and complying with the partner's request. In this way, the treatment targets both production and comprehension. Moreover, as verbal targets increase in linguistic complexity across the protocol ("a ball", "throw a ball"; "Do you have a ball"?), a variety of lexical and phrasal structures are targeted. Studies of CILT have reported gains on multiple language behaviors, supporting its broad engagement of the language network.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Active TMS | Active Comparator | There will be 10 TMS sessions over 2 consecutive weeks in which 30 two-second stimulation trains of 10 Hz TMS will be delivered every 30 seconds to the left inferior pars triangularis and to the left posterior superior left temporal gyrus. Each TMS treatment session will be immediately followed by a 60-90 minute session of Constrained Induced Language Therapy (CILT). |
|
| Sham TMS | Sham Comparator | There will be 10 TMS sessions over 2 consecutive weeks in which 30 two-second stimulation trains of 10 Hz sham TMS will be delivered every 30 seconds to the left inferior pars triangularis and to the left posterior superior left temporal gyrus. Sham TMS will be administered with a sham TMS coil that looks and sounds like the active coil but does not generate a magnetic field. Each TMS treatment session will be immediately followed by a 60-90 minute session of Constrained Induced Language Therapy (CILT). |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Active TMS | Device | Active TMS will be delivered at 100% motor threshold |
| |
| Measure | Description | Time Frame |
|---|---|---|
| Change in WAB-AQ Score | The primary outcome measure will be the change in score on the Western Aphasia Battery Aphasia Quotient (WAB-AQ), a score assessing overall aphasia recovery. Scores can range from 0-100, with higher scores representing better outcomes. 0-25 is very severe, 26-50 is severe, 51-75 is moderate, and 76-above is mild. A score of 93 or higher is considered recovered. | 12 weeks post-treatment |
| Measure | Description | Time Frame |
|---|---|---|
| Change in Percentage of Items Correct on the PNT | The secondary outcome measure will be change in naming accuracy on the Philadelphia Naming Test (PNT). PNT naming accuracy is measured as a percentage from 0% to 100% with higher percentages meaning better naming ability. The task involves naming 175 pictures of common objects. | 12 weeks post-treatment |
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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 |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 21459427 | Background | Hamilton RH, Chrysikou EG, Coslett B. Mechanisms of aphasia recovery after stroke and the role of noninvasive brain stimulation. Brain Lang. 2011 Jul;118(1-2):40-50. doi: 10.1016/j.bandl.2011.02.005. Epub 2011 Apr 2. | |
| 23280015 | Background | Medina J, Norise C, Faseyitan O, Coslett HB, Turkeltaub PE, Hamilton RH. Finding the Right Words: Transcranial Magnetic Stimulation Improves Discourse Productivity in Non-fluent Aphasia After Stroke. Aphasiology. 2012 Sep 1;26(9):1153-1168. doi: 10.1080/02687038.2012.710316. Epub 2012 Aug 29. |
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A total of 11 participants did not qualify at the time of enrollment due to MMSE scores (8) and medical contraindication (3).
One participant dropped out of the study prior to randomization due to travel concerns.
Participants were recruited from 2019-2021 from the Hospital of the University of Pennsylvania and surrounding Philadelphia area medical centers.
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| ID | Title | Description |
|---|---|---|
| FG000 | Active TMS | Participants will receive 10 TMS sessions over 2 consecutive weeks in which 20 minutes of TMS will be delivered to the left inferior pars triangularis and to the left posterior superior left temporal gyrus. Each TMS treatment session will be immediately followed by a 60-90 minute session of Constrained Induced Language Therapy (CILT). |
| FG001 | Sham TMS | Participants will take part in 10 sham TMS sessions over 2 consecutive weeks. Sham TMS mimics the sensory experience (look, sound and feel) of active TMS but does not stimulate the brain. Sham TMS will be administered with a sham TMS coil that looks and sounds like the active coil but does not generate a magnetic field. The sham TMS will target the same two brain locations - left inferior pars triangularis and the left posterior superior left temporal gyrus. Each sham TMS treatment session will be immediately followed by a 60-90 minute session of Constrained Induced Language Therapy (CILT). |
| Title | Milestones | Reasons Not Completed | |||||||||||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Overall Study |
|
|
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| ID | Title | Description |
|---|---|---|
| BG000 | Active TMS | Participants will receive 10 TMS sessions over 2 consecutive weeks in which 20 minutes of TMS will be delivered to the left inferior pars triangularis and to the left posterior superior left temporal gyrus. Each TMS treatment session will be immediately followed by a 60-90 minute session of Constrained Induced Language Therapy (CILT). |
| 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 | Change in WAB-AQ Score | The primary outcome measure will be the change in score on the Western Aphasia Battery Aphasia Quotient (WAB-AQ), a score assessing overall aphasia recovery. Scores can range from 0-100, with higher scores representing better outcomes. 0-25 is very severe, 26-50 is severe, 51-75 is moderate, and 76-above is mild. A score of 93 or higher is considered recovered. | Posted | Mean | Standard Deviation | score on a scale | 12 weeks post-treatment |
|
From baseline, adverse event data were collected over a period of time consisting of 12 weeks.
Adverse event (AEs) information was collected daily during treatment sessions, as well as each follow-up visit.
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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 | Participants will receive 10 TMS sessions over 2 consecutive weeks in which 20 minutes of TMS will be delivered to the left inferior pars triangularis and to the left posterior superior left temporal gyrus. Each TMS treatment session will be immediately followed by a 60-90 minute session of Constrained Induced Language Therapy (CILT). |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Cardiac Arrest | Cardiac disorders | Systematic Assessment | Participant died from cardiac arrest. |
| Term | Organ System | Source Vocabulary | Assessment Type | Notes | Statistical Information |
|---|---|---|---|---|---|
| Headache | General disorders | Systematic Assessment |
Not provided
| Title | Organization | Phone | Extension | |
|---|---|---|---|---|
| Daniela Sacchetti, MS | Clinical Research Coordinator | 215-573-4336 | danielas@pennmedicine.upenn.edu |
Not provided
| Type | Includes Protocol | Includes SAP | Includes ICF | Document Label | Document Date | Document Uploaded Date | Document File Name |
|---|---|---|---|---|---|---|---|
| Prot_SAP | Yes | Yes | No | Study Protocol and Statistical Analysis Plan | Oct 17, 2023 | Aug 20, 2025 | Prot_SAP_000.pdf |
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| ID | Term |
|---|---|
| D000544 | Alzheimer Disease |
| ID | Term |
|---|---|
| D003704 | Dementia |
| D001927 | Brain Diseases |
| D002493 | Central Nervous System Diseases |
| D009422 | Nervous System Diseases |
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Participants will be randomized to either TMS or sham TMS in a 2:1 allocation ratio.
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The individual administering TMS will keep the master file of subject assignments, but all other individuals in contact with the subject or their data will be unaware of group assignment. Participants will not be informed of their assignment to active or sham status.
| CILT |
| Behavioral |
60-90 minutes of CILT will be administered during each treatment session |
|
|
| Sham TMS | Device | Sham TMS will be administered |
|
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| BG001 |
| Sham TMS |
Participants will take part in 10 sham TMS sessions over 2 consecutive weeks. Sham TMS mimics the sensory experience (look, sound and feel) of active TMS but does not stimulate the brain. Sham TMS will be administered with a sham TMS coil that looks and sounds like the active coil but does not generate a magnetic field. The sham TMS will target the same two brain locations - left inferior pars triangularis and the left posterior superior left temporal gyrus. Each sham TMS treatment session will be immediately followed by a 60-90 minute session of Constrained Induced Language Therapy (CILT). |
| BG002 | Total | Total of all reporting groups |
| years |
|
| Sex: Female, Male | Count of Participants | Participants |
|
| Ethnicity (NIH/OMB) | Count of Participants | Participants |
|
| Race (NIH/OMB) | Count of Participants | Participants |
|
| Western Aphasia Battery (WAB-AQ) Score | Mean | Standard Deviation | scores on a scale |
|
| Philadelphia Naming Test, Items Correct | Mean | Standard Deviation | number of items correct |
|
| OG001 | Sham TMS | There will be 10 TMS sessions over 2 consecutive weeks in which 30 two-second stimulation trains of 10 Hz sham TMS will be delivered every 30 seconds to the left inferior pars triangularis and to the left posterior superior left temporal gyrus. Sham TMS will be administered with a sham TMS coil that looks and sounds like the active coil but does not generate a magnetic field. Each TMS treatment session will be immediately followed by a 60-90 minute session of Constrained Induced Language Therapy (CILT). CILT: 60-90 minutes of CILT will be administered during each treatment session Sham TMS: Sham TMS will be administered |
|
|
|
| Secondary | Change in Percentage of Items Correct on the PNT | The secondary outcome measure will be change in naming accuracy on the Philadelphia Naming Test (PNT). PNT naming accuracy is measured as a percentage from 0% to 100% with higher percentages meaning better naming ability. The task involves naming 175 pictures of common objects. | Posted | Mean | Standard Deviation | percentage of correct responses | 12 weeks post-treatment |
|
|
|
|
| 1 |
| 7 |
| 1 |
| 7 |
| 2 |
| 7 |
| EG001 | Sham TMS | Participants will take part in 10 sham TMS sessions over 2 consecutive weeks. Sham TMS mimics the sensory experience (look, sound and feel) of active TMS but does not stimulate the brain. Sham TMS will be administered with a sham TMS coil that looks and sounds like the active coil but does not generate a magnetic field. The sham TMS will target the same two brain locations - left inferior pars triangularis and the left posterior superior left temporal gyrus. Each sham TMS treatment session will be immediately followed by a 60-90 minute session of Constrained Induced Language Therapy (CILT). | 0 | 4 | 0 | 4 | 3 | 4 |
|
| Head Pain | General disorders | Systematic Assessment |
|
| Dizziness | General disorders | Systematic Assessment |
|
| Stomach Ache | Gastrointestinal disorders | Systematic Assessment |
|
| Heart Palpitations | Cardiac disorders | Systematic Assessment |
|
| Fall | General disorders | Systematic Assessment |
|
Not provided
Not provided
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| D024801 |
| Tauopathies |
| D019636 | Neurodegenerative Diseases |
| D019965 | Neurocognitive Disorders |
| D001523 | Mental Disorders |