Primary Progressive Aphasia
Conditions
Keywords
Adult, Primary Progressive Aphasia, High-definition Transcranial Direct Current Stimulation, HD-tDCS, Language, Logopenic, Magnetic Resonance Imaging, MRI, Magnetoencephalography, MEG, Brain, Aphasia
Brief summary
This study aims to evaluate the effectiveness of a therapy called High-Definition Transcranial Direct Current Stimulation (HD-tDCS) for the treatment of the language deficits experienced by people with a type of Primary Progressive Aphasia. This study uses a combination of brain imaging, language assessment, language training sessions, and HD-tDCS therapy as well as placebo therapy sessions.
Detailed description
The logopenic variant of Primary Progressive Aphasia (lvPPA) is an untreatable neurodegenerative disorder that is often referred to as the 'language form' of Alzheimer's Disease (AD). Transcranial Direct Current Stimulation (tDCS) has emerged as a safe and potentially effective tool that appears to enhance language production when delivered during language training. This technology provides a critical opportunity to conduct disease intervention. In this study, the investigators will test the hypothesis that High-Definition tDCS (HD-tDCS) will improve performance on language tasks by increasing functional connectivity and by regulating abnormal neuronal oscillatory patterns. The rationale for this project is that a determination of the therapeutic efficacy and the associated neural mechanisms of HD-tDCS in lvPPA is likely to offer a scientific framework whereby new stimulation parameters, conditions, and target sites can be deciphered. This study will test the hypothesis that HD-tDCS will improve performance on language tasks by increasing functional connectivity and by regulating abnormal neuronal oscillatory patterns. The language performance and functional connectivity changes will be determined in a randomized, double-blind, sham-controlled crossover manner, in which a stimulation of up to 2mA in the targeted cortical tissue or sham is administered to 20 lvPPA subjects age 45 years and older. The order of treatments is counterbalanced in a within-subject crossover design. In brief, study participants will receive sham during one treatment period and stimulation during the other treatment period.
Interventions
DEVICEHD-tDCS
High-Dose transcranial Direct Current Stimulation
DEVICESham
Sham sessions (no electric current)
Sponsors
Medical College of Wisconsin
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
An unblinded member of the study team will randomize participants to the treatment conditions. Study Group assignment will be based on random number generation (in blocks of 4) followed by the creation of numbered envelopes. Participants and the study team members involved in language training, tDCS delivery, and assessment of outcomes will be blind to the treatment received.
Intervention model description
This is a randomized, double-blind, sham-controlled trial in which stimulation or sham will be administered to 20 subjects over the age of 45 years, with the order of treatments counterbalanced in a within-subject crossover design. Stimulation and sham sessions last 20 minutes and occur for 10 days over a 2-week period.
Eligibility
Sex/Gender
ALL
Age
45 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosed with language variant Primary Progressive Aphasia (lvPPA) subtype, defined as either clinical lvPPA or imaging-supported lvPPA in accordance with the most recent diagnostic criteria (Mesulam., 2001; Gorno-Tempini et al., 2011). * Fluent in English. * 45 years of age or older. * Structural brain MRI performed within 3 years prior to enrollment.
Exclusion criteria
* Severe cognitive, auditory or visual impairments that would preclude cognitive testing. * Presence of major untreated or unstable psychiatric disease. * A chronic medical condition that is not treated or is unstable. * The presence of cardiac stimulators or pacemakers. * Any metal implants in the skull * Contraindications to MRI * History of seizures * History of dyslexia or other developmental learning disabilities.
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Determine Changes in Language Performance After Stimulation Sessions | Language performance was assessed before and after 2-week intervention and during washout periods | Language performance as assessed at baseline and post-stimulation procedure |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Determine the Resting State Language Network-level Changes in Left TPC Functional Connectivity. | Language network resting state changes were assessed before and after 2-week intervention and during washout periods | Language network resting state changes after stimulation procedure |
| Determine the Neuronal Frequency Distribution and Connectivity Measures Associated With the Left TPC as Assessed by MEG. | Resting-state neuronal frequencies and synchronizations changes were assessed before and after 2-week intervention and during washout periods | Resting-state neuronal frequencies and synchronizations changes after stimulation procedure |
Countries
United States
Participant flow
Recruitment details
6 patients were screened for eligibility between 02/24/2020 and 05/18/2022.
Pre-assignment details
5 of 6 subjects were randomized. 1 subject withdrew themselves prior to starting baseline procedures.
Participants by arm
| Arm | Count |
|---|---|
| HD-tDCS, Then Sham Subjects receive High Dose transcranial Direct Current Stimulation (HD-tDCS) lasting 20 minutes at an electric current intensity of up to 2mA in the left posterior temporo-parietal cortex (TPC). Stimulation sessions are delivered once a day (QD) for a total of 10 sessions over 2 weeks (Monday-Friday). After a washout period of 16 weeks, subjects receive Sham sessions (no electric current) once a day (QD) for a total of 10 sessions over 2 weeks (Monday-Friday).
HD-tDCS: High-Dose transcranial Direct Current Stimulation
Sham: Sham sessions (no electric current) | 2 |
| Sham, Then HD-tDCS Subjects receive Sham sessions (no electric current) once a day (QD) for a total of 10 sessions over 2 weeks (Monday-Friday). After a washout period of 16 weeks, subjects receive High Dose transcranial Direct Current Stimulation (HD-tDCS) lasting 20 minutes at an electric current intensity of up to 2mA in the left posterior temporo-parietal cortex (TPC). Stimulation sessions are delivered once a day (QD) for a total of 10 sessions over 2 weeks (Monday-Friday).
HD-tDCS: High-Dose transcranial Direct Current Stimulation
Sham: Sham sessions (no electric current) | 3 |
| Total | 5 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | HD-tDCS, Then Sham | Sham, Then HD-tDCS | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 1 Participants | 2 Participants | 3 Participants |
| Age, Categorical Between 18 and 65 years | 1 Participants | 1 Participants | 2 Participants |
| Age, Continuous | 70.0 years STANDARD_DEVIATION 8.49 | 66.3 years STANDARD_DEVIATION 3.06 | 67.8 years STANDARD_DEVIATION 5.17 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 2 Participants | 3 Participants | 5 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 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 | 2 Participants | 3 Participants | 5 Participants |
| Region of Enrollment United States | 2 participants | 3 participants | 5 participants |
| Sex: Female, Male Female | 1 Participants | 1 Participants | 2 Participants |
| Sex: Female, Male Male | 1 Participants | 2 Participants | 3 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 4 | 0 / 4 |
| other Total, other adverse events | 2 / 4 | 1 / 4 |
| serious Total, serious adverse events | 1 / 4 | 0 / 4 |
Outcome results
Primary
Determine Changes in Language Performance After Stimulation Sessions
Language performance as assessed at baseline and post-stimulation procedure
Time frame: Language performance was assessed before and after 2-week intervention and during washout periods
Population: No data were collected for this outcome measure.
Secondary
Determine the Neuronal Frequency Distribution and Connectivity Measures Associated With the Left TPC as Assessed by MEG.
Resting-state neuronal frequencies and synchronizations changes after stimulation procedure
Time frame: Resting-state neuronal frequencies and synchronizations changes were assessed before and after 2-week intervention and during washout periods
Population: No data were collected for this outcome measure.
Secondary
Determine the Resting State Language Network-level Changes in Left TPC Functional Connectivity.
Language network resting state changes after stimulation procedure
Time frame: Language network resting state changes were assessed before and after 2-week intervention and during washout periods
Population: No data were collected for this outcome measure.