Primary Progressive Aphasia
Conditions
Keywords
transmagnetic stimulation, functional MRI guided Theta Burst Stimulation
Brief summary
Frontotemporal degeneration (FTD) is a non-Alzheimer's dementia that is the 2nd most common cause of dementia in the United States. FTD may present with focal language symptoms that are clinically described as primary progressive aphasia (PPA). There are two types of PPA associated with FTD-semantic variant primary progressive aphasia (SV-PPA) and nonfluent/agrammatic variant primary progressive aphasia (NFV-PPA). Both diseases are progressive neurodegenerative disease processes that compromise dominant hemisphere large scale brain network function, ultimately resulting in mutism. There are currently no FDA-approved treatments for PPA and management is mostly supportive. In combination with resting state functional MRI (rs-fMRI), transcranial magnetic stimulation (TMS) with intermittent theta burst stimulation (iTBS) offers a non-invasive alternative to pharmacotherapy in persons with PPA. In our prior studies of Alzheimer's disease (AD) and Lewy body Dementia (LBD) subjects, investigators have determined that the anterior temporal pole (area TGd and TGv) is an area that is commonly dysfunctional in dementia. The investigators have already embarked upon an fMRI guided study of iTBS in early stage Alzheimer's disease where subjects received a series of 5 treatments to distinct brain regions inclusive of area TGd. The investigators propose a case study of 3 PPA studies where rs-fMRI is applied to the large-scale language networks.
Interventions
DEVICEIntermittent theta burst stimulation
MagVenture TMS Therapy with theta burst stimulation. Resting motor threshold: 80%; Number of pulses per session: 1200 pulses; Inter-train interval: 8 seconds; Pulse frequency in burst: 50 Hertz
Sponsors
HealthPartners Institute
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
40 Years to 90 Years
Healthy volunteers
No
Inclusion criteria
1. Established diagnosis of NFV-PPA and SV-PPA based on criteria (Gorno-Tempini et al., 2011) 2. Prior brain imaging performed 3. Mini Mental Status Exam (MMSE)\>10 4. Subjects are between 40-90 years of age
Exclusion criteria
1. Non-FTD dementia including, but not limited to Alzheimer's, disease, Lewy body dementia, frontotemporal dementia, vascular dementia, Jakob-Creutzfeldt disease, etc. 2. Inability to tolerate rs-fMRI 3. Contraindication of rs-fMRI due to implants or metal 4. Seizure disorder
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Connectivity Measures of the Left TGd, 55b, and STV Parcellations at Baseline and Post-treatment | 6 weeks | The difference and corresponding 95% confidence interval between follow-up and baseline connectivity measures of the TGd parcellations. Range: -1 to 1. Positive values indicate areas where connectivity is higher than healthy controls from the Human Connectome Project. |
Countries
United States
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Intermittent Theta Burst Stimulation All subjects will receive treatment with intermittent theta burst stimulation (iTBS). There will be a total of 5 treatments over a 2-week period. All subjects will receive iTBS to the right TGd region. TBS treatment will also be provided for two additional sites within the large-scale brain networks (LSBNs) that is found to contain the greatest number of connectivity anomalies. Total participation will be 8-10 weeks.
Intermittent theta burst stimulation: MagVenture TMS Therapy with theta burst stimulation. Resting motor threshold: 80%; Number of pulses per session: 1200 pulses; Inter-train interval: 8 seconds; Pulse frequency in burst: 50 Hertz | 3 |
| Total | 3 |
Baseline characteristics
| Characteristic | Intermittent Theta Burst Stimulation |
|---|---|
| Age, Categorical <=18 years | 0 Participants |
| Age, Categorical >=65 years | 2 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants |
| Age, Continuous | 72 years STANDARD_DEVIATION 11 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 3 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Mini-Mental State Examination (MMSE) | 25.3 units on a scale STANDARD_DEVIATION 3.21 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants |
| Race (NIH/OMB) White | 3 Participants |
| Sex: Female, Male Female | 2 Participants |
| Sex: Female, Male Male | 1 Participants |
Adverse events
| Event type | EG000 affected / at risk |
|---|---|
| deaths Total, all-cause mortality | 0 / 3 |
| other Total, other adverse events | 3 / 3 |
| serious Total, serious adverse events | 0 / 3 |
Outcome results
Primary
Connectivity Measures of the Left TGd, 55b, and STV Parcellations at Baseline and Post-treatment
The difference and corresponding 95% confidence interval between follow-up and baseline connectivity measures of the TGd parcellations. Range: -1 to 1. Positive values indicate areas where connectivity is higher than healthy controls from the Human Connectome Project.
Time frame: 6 weeks
| Arm | Measure | Group | Value (MEAN) |
|---|---|---|---|
| Intermittent Theta Burst Stimulation | Connectivity Measures of the Left TGd, 55b, and STV Parcellations at Baseline and Post-treatment | LTgD | .03 correlation |
| Intermittent Theta Burst Stimulation | Connectivity Measures of the Left TGd, 55b, and STV Parcellations at Baseline and Post-treatment | L55b | -.06 correlation |
| Intermittent Theta Burst Stimulation | Connectivity Measures of the Left TGd, 55b, and STV Parcellations at Baseline and Post-treatment | LSTV | -.01 correlation |
Post Hoc
Change in Abnormal Connections of Parcellations
Assessed by calculating the difference and standard deviation between follow-up and baseline of number of abnormal connections of the parcellations. Range: 0-378. There are 378 possible connections of the parcellation. Higher values indicate more abnormal connections of the parcellation pre and post-treatment. The change in the number of abnormal connections of the parcellation is reported.
Time frame: 6 weeks
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Intermittent Theta Burst Stimulation | Change in Abnormal Connections of Parcellations | L55b | 7 abnormal connections | Standard Deviation 13.7 |
| Intermittent Theta Burst Stimulation | Change in Abnormal Connections of Parcellations | LTgD | 2 abnormal connections | Standard Deviation 7 |
| Intermittent Theta Burst Stimulation | Change in Abnormal Connections of Parcellations | LSTV | 3.6 abnormal connections | Standard Deviation 10.7 |