NCT03887481 Targeting Language-specific and Executive-control Networks With Transcranial Direct Current Stimulation in Logopenic Variant PPA
| NCT ID | NCT03887481 |
| Status | Recruiting |
| Phase | — |
| Sponsor | Johns Hopkins University |
| Condition | Logopenic Progressive Aphasia |
| Study Type | INTERVENTIONAL |
| Enrollment | 60 participants |
| Start Date | 2022-10-15 |
| Primary Completion | 2027-10-31 |
Eligibility & Interventions
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What to Expect as a Participant
You will actively receive the study intervention — which may be a drug, biologic, device, or procedure.
This trial targets 60 participants in total. It began in 2022-10-15 with a primary completion date of 2027-10-31.
⚠ This information is for research awareness only. Always consult your physician before joining any clinical trial. Participation is voluntary and you may withdraw at any time.
Brief Summary
AD afflicts over 5.5. million Americans and is one of the most expensive diseases worldwide. In AD the variant in which language functions are most affected are referred to as 'logopenic variant Primary Progressive Aphasia' (lvPPA). Language deficits dramatically impair communication and quality of life for both patients and caregivers. PPA usually has an early onset (50-65 years of age), detrimentally affecting work and family life. Studies have identified verbal short-term memory/working memory (vSTM/WM) as a primary deficit and cause of language impairment. In the first cycle of this award, the investigators asked the question of whether language therapy effects could be augmented by electrical stimulation. The investigators conducted the largest to-date randomized, double-blind, sham-controlled, crossover, clinical trial to determine the effects of transcranial direct current stimulation (tDCS) in PPA. The investigators found that tDCS over the left inferior frontal gyrus (L\_IFG), one of the major language hubs in the brain, significantly enhanced the effects of a written naming and spelling intervention. In addition, findings demonstrated that tDCS modulates functional connectivity between the stimulated area and other networks (e.g. functionally and structurally connected areas), and that tDCS modulates the inhibitory neurotransmitter gamma-aminobutyric acid (GABA). In terms of tDCS, the investigators have been identified several predictors to determine the beneficience of tDCS including (a) PPA variant, (b) initial performance on cognitive/language tasks, particularly vSTM/WM, and (c) initial white-matter integrity and structure. These findings support the notion that tDCS benefits generalize beyond the treatment tasks and has led to the important question of the present study: How can we implement treatments to product benefits that maximally generalize to untrained but vital language/cognitive functions. To address the above question, the investigators will test recent neuroplasticity theories that claim that the benefits of neuromodulation to language-specific areas generalize to other language functions within the language network, while neuromodulation of a domain-general/multiple-demands area generalizes to both domain-general, executive and language functions. The two areas to be stimulated will be the supramarginal gyrus (SMG) and left dorsolateral prefrontal cortex (DLPFC) respectively. The left supramarginal gyrus (L\_SMG) in particular, specializes in phonological processing, namely phonological verbal short-term memory (vSTM), i.e., the ability to temporarily store phonological (and graphemic) information in order. The domain of vSTM affects many language tasks (repetition, naming, syntax), which makes it an ideal treatment target and the L\_SMG an ideal stimulation target, since generalization of tDCS effects to other language tasks is driven by the function (computation) of the stimulated area. By testing a fundamental principle of neuromodulation in a devastating neurodegenerative disorder, the investigators will significantly advance the field of neurorehabilitation in early-onset dementias. Aim 1: To determine whether vSTM/WM behavioral therapy combined with high definition (HD)-tDCS over the L\_SMG will induce more generalization to language-specific tasks than to executive tasks, whereas stimulation over the LDPFC will induce equivalent generalization to both executive and language-specific tasks. Aim 2: To understand the mechanism of tDCS by measuring tDCS-induced changes in network functional connectivity (FC) and GABA in the LSMG and LDPFC. The investigators will carry out resting-state functional magnetic resonance imaging (rsfMRI), (MPRAGE), diffusion-weighted imaging (DWI), perfusion imaging (pCASL), and magnetic resonance spectroscopy (MRS), before, after, and 3-months post-intervention. Aim 3: To identify the neural, cognitive, physiological, clinical and demographic characteristics (biomarkers) that predict sham, tDCS, and tDCS vs. sham effects on vSTM and related language tasks in PPA. The investigators will evaluate neural (functional and structural connectivity, cortical volume, neuropeptides, and perfusion), cognitive (memory, attention, executive) and language functions, clinical (severity), physiological (sleep), and demographic (age, gender) characteristics, and the investigators will analyze the effects on vSTM and other language/cognitive outcomes immediately after intervention and at 3 months post-intervention.
Eligibility Criteria
Inclusion Criteria: * Must be between 50-80 years of age. * Must be right-handed. * Must be proficient in English. * Must have a minimum of high-school education. * Must be diagnosed with Primary Progressive Aphasia (PPA) or dementia. * Participants will be diagnosed with PPA or with any of the PPA variants in specialized or early dementias clinics at Johns Hopkins University or other specialized centers in the US based on the current consensus criteria. * Healthy age- and education-matched controls: The investigators will include 30 healthy age- and education-matched controls, usually spouses, to maximize similarity in terms of other demographic or life-style factors that contribute to language and cognitive performance. Exclusion Criteria: * People with previous neurological disease including vascular dementia (e.g., stroke, developmental dyslexia, dysgraphia or attentional deficit). * People with uncorrected hearing loss * People with uncorrected visual acuity loss. * People with advanced dementia or severe language impairments: Mini Mental State -Examination (MMSE)\<18, or Montreal Cognitive Assessment (MOCA)\<15, or language Frontotemporal Dementia specific - Clinical Dementia Rating (FTD-CDR)\<=2. * Left handed individuals. * People with pre-existing psychiatric disorders such as behavioral disturbances, severe depression, or schizophrenia that do not allow these people to comply or follow the study schedule and requirements such as repeated evaluation and therapy. Exclusion Criteria for MRI Participation: * People with severe claustrophobia. * People with cardiac pacemakers or ferromagnetic implants. * Pregnant women.
Contact & Investigator
Kyrana Tsapkini, PhD
PRINCIPAL INVESTIGATOR
Johns Hopkins University
Frequently Asked Questions
Who can join the NCT03887481 clinical trial?
This trial is open to participants of all sexes, aged 50 Years or older, up to 80 Years, studying Logopenic Progressive Aphasia. Full inclusion and exclusion criteria are listed in the Eligibility Criteria section. Always confirm your eligibility with the research team before applying.
Is NCT03887481 currently recruiting?
Yes, NCT03887481 is actively recruiting participants. Contact the research team at cesiad@jhmi.edu for enrollment information.
Where is the NCT03887481 trial being conducted?
This trial is being conducted at Baltimore, United States.
Who is sponsoring the NCT03887481 clinical trial?
NCT03887481 is sponsored by Johns Hopkins University. The principal investigator is Kyrana Tsapkini, PhD at Johns Hopkins University. The trial plans to enroll 60 participants.