While many have strongly suggested that transcranial direct current stimulation (tDCS) may represent a beneficial intervention for patients with primary progressive aphasia (PPA), this promising technology has not yet been applied widely in clinical settings. This treatment gap is underscored by the absence of any neurally-focused standard-of-care treatments to mitigate the devastating impact of aphasia on patients' family, work, and social lives. Given that tDCS is inexpensive, easy to use (it is potentially amenable to home use by patients and caregivers), minimally invasive, and safe there is great promise to advance this intervention toward clinical use. The principal reason that tDCS has not found wide clinical application yet is that its efficacy has not been tested in large, multi-center, clinical trials. In this study, scientists in the three sites that have conducted tDCS clinical trials in North America-Johns Hopkins University and the University of Pennsylvania in the US, and the University of Toronto in Canada, will collaborate to conduct a multi-site, Phase II clinical trial of tDCS a population in dire need of better treatments.
Presence of aphasia attributable to non-fluent PPA or logopenic PPA
High school education (or more)
Between the ages of 50 and 90
Must be able to understand the nature of the study and give informed consent
Cognitive impairment of sufficient severity to preclude giving informed consent (Mini Mental State Examination [MMSE] less than 15)
Any unrelated neurologic or physical condition that impairs communication ability
History of unrelated neurological conditions, including but not limited to traumatic brain injury (TBI), stroke, or small vessel disease, that has resulted in a neurologic deficit
Any additional neurological condition that would likely reduce the safety of study participation, including central nervous system (CNS) vasculitis, intracranial tumor, intracranial aneurysm, multiple sclerosis, or arteriovenous malformations
Crossover
Active tDCS + Language Therapy
DeviceActive tDCS stimulation will be delivered by a battery-driven constant current stimulator. The electrical current will be administered to a pre-specified region of the brain (inferior frontal gyrus). The stimulation will be delivered at an intensity of 2mA (estimated current density 0.04 milliamps (mA)/cm2; estimated total charge 0.048 Coulombs (C)/cm2) in a ramp-like fashion for a maximum of 20 minutes. Language therapy will be conducted in conjunction with stimulation and will target oral and written naming.
Sham tDCS + Language Therapy
DeviceDuring sham stimulation, current will be administered in a ramp-line fashion but after the ramping the intensity will drop to 0 mA. Language therapy targeting oral and written naming will be administered during sham tDCS stimulation.
Immediate Change in Phonemic Accuracy
The primary outcome measure will be tDCS-induced change in performance on phonemic accuracy of trained items. Phonemic accuracy will be calculated on a scale of 0-100% with a higher number reflecting higher accuracy. The change in performance from baseline will be compared between the tDCS condition and the sham condition.
Immediate Change in Letter Accuracy
The primary outcome measure will be tDCS-induced change in performance on letter accuracy of trained items. Letter accuracy will be calculated on a scale of 0-100% with a higher number reflecting higher accuracy. The change in performance from baseline will be compared between the tDCS condition and the sham condition.
Change in Phonemic Accuracy at 3-month follow-up visit
The primary outcome measure will be tDCS-induced change in performance on phonemic accuracy of trained items, 3 months following the discontinuation of intervention. Phonemic accuracy will be calculated on a scale of 0-100% with a higher number reflecting higher accuracy. The change in performance from baseline will be compared between the tDCS condition and the sham condition.
Change in Letter Accuracy at 3-month follow-up visit
The primary outcome measure will be tDCS-induced change in performance on letter accuracy of trained items, 3 months following the discontinuation of intervention. Letter accuracy will be calculated on a scale of 0-100% with a higher number reflecting higher accuracy. The change in performance from baseline will be compared between the tDCS condition and the sham condition.
Change in Untrained Naming Items (phonemic accuracy)
The outcome measure will be tDCS-induced change of phonemic accuracy of untrained stimuli (those not targeted in therapy). Phonemic accuracy will be calculated on a scale of 0-100% with a higher number reflecting higher accuracy. The change in performance from baseline will be compared between the tDCS condition and the sham condition.
Change in Untrained Naming Items (letter accuracy)
The outcome measure will be tDCS-induced change of letter accuracy of untrained stimuli (those not targeted in therapy). Letter accuracy will be calculated on a scale of 0-100% with a higher number reflecting higher accuracy. The change in performance from baseline will be compared between the tDCS condition and the sham condition.
Change in functional connectivity of select brain regions (z-correlations)
Using resting stage functional MRI (rs-fMRI) investigators will detect activity of various brain regions under a resting/task-negative condition, which will help evaluate functional regional interactions as indicated by the z-correlations between the selected brain area.
Change in volumetric measurements of select brain regions
Using Magnetization-Prepared Rapid Gradient-Echo (MPRAGE) Magnetic Resonance Imaging (MRI) investigators will perform volumetric measurements of select brain regions. Measurements will be collected in millimeters cubed (mm\^3).
Change in location of white matter tracts of select brain regions
Using Diffusion Tensor Imaging (DTI) investigators will estimate the location of the brain's white matter tracts on the regions of concern.
Change in anisotropy of white matter tracts of select brain regions
Using Diffusion Tensor Imaging (DTI) investigators will estimate the anisotropy of the brain's white matter tracts on the brain regions of concern.
Bilingualism as assessed by the Language Experience and Proficiency Questionnaire
Language status and language history will be assessed using the Language Experience and Proficiency Questionnaire (LEAP-Q). For those participants who are bi-/multilingual, we will determine their premorbid relative proficiency between languages by subtracting LEAP-Q ratings for L2 from L1, with ratings close to 0 indicating a relative balance between the languages, positive scores indicating an L1 dominance, and negative scores indicating an L2 dominance. We will compare behavioral results of bi-/multilingual individuals to those who are monolingual.
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Johns Hopkins University
Lead sponsor
National Institute on Aging (NIA)
Collaborator
