Primary Progressive Aphasia
Conditions
Brief summary
In the present sham-controlled study, the investigators examine whether tDCS could be used to enhance language abilities (e.g., picture naming) in individuals with primary progressive aphasia (PPA) primarily characterized by difficulties with speech production.
Detailed description
Primary Progressive Aphasia (PPA) is a neurodegenerative condition characterized by insidious irreversible loss of language abilities. Prior studies suggest that transcranial direct current stimulation (tDCS) directed toward language areas of the brain may help to ameliorate symptoms of PPA. In the current study, the investigators are examining whether tDCS could be used to enhance language abilities (e.g., picture naming) in individuals with PPA variants primarily characterized by difficulties with speech production (non-fluent and logopenic). Participants are being recruited from the Penn Frontotemporal Dementia Center to receive 10 days of both real and sham tDCS (counter-balanced, full-crossover design; participants are naïve to stimulation condition). A battery of language tests are being administered at baseline, immediately post-tDCS (real and sham), and six weeks and twelve weeks following stimulation. Real tDCS may improve language performance in some individuals with PPA. Specifically, the investigators expect that tDCS will be more effective in people whose baseline performance is worse based on previous research. Severity of deficits at baseline may be an important factor in predicting which patients will respond positively to language-targeted tDCS therapies.
Interventions
DEVICEtranscranial direct current stimulation
Transcranial direct current stimulation (tDCS) is a type of noninvasive brain stimulation that modulates the resting excitability of neuronal populations, thereby altering patterns of brain activity in potentially behaviorally relevant ways. The stimulation involves 20 minutes of constant stimulation at 1.5 mA.
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
45 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* Between the ages of 45-80 * Native English speaker * Diagnosed with Primary Progressive Aphasia * Subject understands nature of study and able to give informed consent
Exclusion criteria
* Cognitive impairment of sufficient severity to preclude giving informed consent * History of seizures or unexplained loss of consciousness * Previous craniotomy or any breach of the skull * Metallic objects in the head or face other than dental braces, fillings or implants * Pacemaker or implantable cardioverter-defibrillator * Pregnant
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Aphasia Severity (WAB-AQ): Effects of Active tDCS (Baseline vs. 0 Weeks Immediately Following Stimulation) | Difference in WAB-AQ from Baseline at 0-weeks Post-stimulation | The Western Aphasia Battery (WAB) was administered at baseline and immediately post-tDCS (real; sham) following the termination of the tDCS session on the same day (0 week). We computed WAB-Aphasia Quotient (WAB-AQ), a measure of overall aphasia severity with higher scores indicating better language performance. The WAB assesses the following language domains in subtests: fluency, comprehension, repetition, and naming. We examined change in WAB-AQ and each of the sub-tests from baseline. Difference scores were computed by subtracting the post-intervention score (0 weeks) from baseline for each study arm to assess the impact of real/active vs sham tDCS on severity and each sub-test. Scale title: WAB-AQ; scale values: 0-100; higher scores=better outcome. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Naming Ability (WAB Naming Subtest): Effects of Active tDCS Baseline vs. 0 Weeks Immediately Following Stimulation | Difference in WAB Naming Subtest from Baseline at 0-weeks Post-stimulation | WAB-naming subtest used common objects as stimuli. Participants were required to name the objects. Three-point maximum score could be earned for each stimulus and a total of 60-points could be earned on this task; points were deducted if the response was incorrect and required a cue or if the response included a paraphasia. |
Countries
United States
Participant flow
Recruitment details
Recruitment period: 10/2017-11/2019. Patients with Primary Progressive Aphasia will be recruited from the clinical practices of Drs. H. Branch Coslett, Roy Hamilton, and Murray Grossman at the Hospital of the University of Pennsylvania. Additional recruitment measures involve flyers posted around the University of Pennsylvania campus and the Hospital of the University of Pennsylvania grounds, as well as online FTD/PPA support groups and in-person support groups around the Philadelphia area.
Pre-assignment details
16 participants were enrolled in the study. Subjects were enrolled if they were native English speakers, right handed, and received a diagnosis of primary progressive aphasia (PPA). Note that one participant was diagnosed as having PPA at the time of enrollment; however, it was later learned that this was a misdiagnosis and their data were not analyzed. Baseline Characteristics reported for N=13. The washout period between treatment arms was 12 weeks.
Participants by arm
| Arm | Count |
|---|---|
| Active tDCS, Then Sham Transcranial direct current stimulation (tDCS) is a type of noninvasive brain stimulation that modulates the resting excitability of neuronal populations, thereby altering patterns of brain activity in potentially behaviorally relevant ways. The active stimulation condition involves 20 minutes of constant stimulation at 1.5 mA. Arm 1 data were collected prior to active tDCS, whereas Arm 2 data reflect performance 12 weeks following active tDCS (prior to crossing over to the sham tDCS treatment arm). | 7 |
| Sham tDCS, Then Active Sham tDCS uses identical stimulation parameters as the active condition, however terminates after 30 seconds in order to mimic the sensation of real tDCS. Arm 1 data were collected prior to sham tDCS, whereas Arm 2 data reflect performance 12 weeks following sham tDCS (prior to crossing over to the active tDCS treatment arm). | 6 |
| Total | 13 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Arm 2 | Withdrawal by Subject | 1 | 0 |
Baseline characteristics
| Characteristic | Active tDCS, Then Sham | Sham tDCS, Then Active | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 4 Participants | 4 Participants | 8 Participants |
| Age, Categorical Between 18 and 65 years | 3 Participants | 2 Participants | 5 Participants |
| Age, Continuous | 66.29 years STANDARD_DEVIATION 7.67 | 66.33 years STANDARD_DEVIATION 6.18 | 66.31 years STANDARD_DEVIATION 6.73 |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 2 Participants | 2 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 7 Participants | 4 Participants | 11 Participants |
| Region of Enrollment United States | 7 participants | 6 participants | 13 participants |
| Sex: Female, Male Female | 3 Participants | 2 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 4 Participants | 8 Participants |
| Western Aphasia Battery - Aphasia Quotient (WAB-AQ) Arm 1 | 79.84 units on a scale STANDARD_DEVIATION 9.68 | 85.55 units on a scale STANDARD_DEVIATION 7.8 | 82.38 units on a scale STANDARD_DEVIATION 9.61 |
| Western Aphasia Battery - Aphasia Quotient (WAB-AQ) Arm 2 | 78.39 units on a scale STANDARD_DEVIATION 9.24 | 85.55 units on a scale STANDARD_DEVIATION 7.02 | 81.23 units on a scale STANDARD_DEVIATION 10.1 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 16 | 0 / 16 |
| other Total, other adverse events | 0 / 16 | 0 / 16 |
| serious Total, serious adverse events | 0 / 16 | 0 / 16 |
Outcome results
Primary
Aphasia Severity (WAB-AQ): Effects of Active tDCS (Baseline vs. 0 Weeks Immediately Following Stimulation)
The Western Aphasia Battery (WAB) was administered at baseline and immediately post-tDCS (real; sham) following the termination of the tDCS session on the same day (0 week). We computed WAB-Aphasia Quotient (WAB-AQ), a measure of overall aphasia severity with higher scores indicating better language performance. The WAB assesses the following language domains in subtests: fluency, comprehension, repetition, and naming. We examined change in WAB-AQ and each of the sub-tests from baseline. Difference scores were computed by subtracting the post-intervention score (0 weeks) from baseline for each study arm to assess the impact of real/active vs sham tDCS on severity and each sub-test. Scale title: WAB-AQ; scale values: 0-100; higher scores=better outcome.
Time frame: Difference in WAB-AQ from Baseline at 0-weeks Post-stimulation
Population: Participants who completed both arms of the study to the 0-week follow-up (N=13). Of the 16 participants enrolled, 3 were excluded from the 0-week follow-up for the following reasons: withdrew prior to starting treatment arm 1 (n=2) and misdiagnosed as PPA (n=1).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active tDCS, Then Sham tDCS | Aphasia Severity (WAB-AQ): Effects of Active tDCS (Baseline vs. 0 Weeks Immediately Following Stimulation) | Arm 2: 0 Week Follow-up | 1.98 score on a scale | Standard Deviation 2.75 |
| Active tDCS, Then Sham tDCS | Aphasia Severity (WAB-AQ): Effects of Active tDCS (Baseline vs. 0 Weeks Immediately Following Stimulation) | Arm 1: 0 Week Follow-up | 2.68 score on a scale | Standard Deviation 2.04 |
| Sham tDCS, Then Active tDCS | Aphasia Severity (WAB-AQ): Effects of Active tDCS (Baseline vs. 0 Weeks Immediately Following Stimulation) | Arm 2: 0 Week Follow-up | 2.25 score on a scale | Standard Deviation 2.04 |
| Sham tDCS, Then Active tDCS | Aphasia Severity (WAB-AQ): Effects of Active tDCS (Baseline vs. 0 Weeks Immediately Following Stimulation) | Arm 1: 0 Week Follow-up | .87 score on a scale | Standard Deviation 2.83 |
Comparison: Repeated-measures analysis of variance (RM-ANOVA) with Condition (active, sham) and time point (baseline, 0-week) as within-subject factors. Analysis tests whether active vs. sham stimulation confers a greater improvement in overall language ability, as measured by the Western Aphasia Battery Aphasia Quotient (WAB-AQ), that endures over time.p-value: 0.14ANOVA
Secondary
Naming Ability (WAB Naming Subtest): Effects of Active tDCS Baseline vs. 0 Weeks Immediately Following Stimulation
WAB-naming subtest used common objects as stimuli. Participants were required to name the objects. Three-point maximum score could be earned for each stimulus and a total of 60-points could be earned on this task; points were deducted if the response was incorrect and required a cue or if the response included a paraphasia.
Time frame: Difference in WAB Naming Subtest from Baseline at 0-weeks Post-stimulation
Population: Participants who completed both arms of the study to the 0-week follow-up (N=13). Of the 16 participants enrolled, 3 were excluded from the 0-week follow-up for the following reasons: withdrew prior to starting treatment arm 1 (n=2) and misdiagnosed as PPA (n=1).
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Active tDCS, Then Sham tDCS | Naming Ability (WAB Naming Subtest): Effects of Active tDCS Baseline vs. 0 Weeks Immediately Following Stimulation | Arm 1: 0-week Follow-up | .63 score on a scale | Standard Deviation 0.49 |
| Active tDCS, Then Sham tDCS | Naming Ability (WAB Naming Subtest): Effects of Active tDCS Baseline vs. 0 Weeks Immediately Following Stimulation | Arm 2: 0-week Follow-up | .26 score on a scale | Standard Deviation 0.83 |
| Sham tDCS, Then Active tDCS | Naming Ability (WAB Naming Subtest): Effects of Active tDCS Baseline vs. 0 Weeks Immediately Following Stimulation | Arm 1: 0-week Follow-up | .11 score on a scale | Standard Deviation 0.59 |
| Sham tDCS, Then Active tDCS | Naming Ability (WAB Naming Subtest): Effects of Active tDCS Baseline vs. 0 Weeks Immediately Following Stimulation | Arm 2: 0-week Follow-up | .63 score on a scale | Standard Deviation 0.35 |
Comparison: Repeated-measures analysis of variance (RM-ANOVA) with Condition (active, sham) and time point (baseline, 0-weeks) as within-subject factors. Analysis tests whether active vs. sham stimulation confers a greater improvement in naming ability, as measured by the naming subtest of the WAB, that endures over time.p-value: 0.02ANOVA