Personalized Closed-Loop Brain Stimulation for Patients With Primary Progressive Aphasia

NCT07511179 | Not Yet Recruiting FDA Device

• 1 other identifier: IRB00557243
• Study Type: interventional
• Target: 10
• Locations: 1 country
• Sites: 1

Brief Summary

This research study investigates the feasibility and efficacy of a personalized, closed-loop electroencephalogram-transcranial electrical stimulation (EEG-tES) intervention for individuals with Primary Progressive Aphasia (PPA), addressing the inconsistent results of generic brain stimulation protocols. By integrating artificial intelligence (AI)-derived insights with real-time data, the study aims to customize transcranial electrical stimulation (tES) parameters, including electrode placement, intensity, and frequency to target the specific brain regions responsible for abnormal signaling in each participant. Over the intervention period paired with computerized cognitive training, the project will evaluate improvements in learning, memory, and functional connectivity, while simultaneously identifying clinical and physiological predictors to determine the viability of transitioning this low-cost, non-invasive technology into a remotely supervised, home-based therapy setting. The study duration will be a total of 6-8 weeks.

Conditions

PPA

Keywords

PPA; EEG; tES; Personalized treatment; Closed-loop

Outcome Measures

Primary Outcomes (8)

• Change in auditory recall accuracy based on the sum of words recalled in Trials 1-5 of semantically related - trained word-lists

  Each trained word-list (practiced during the intervention period) will consist of 12 semantically related words (e.g., birds). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to learn each list. The investigators will compute the raw score of items correctly recalled by summing all scores from Trial 1 to Trial 5 and transforming to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.

  Before intervention, immediately after intervention and 1 month post intervention

• Change in auditory delayed recall accuracy of semantically related - trained word-lists

  Each trained word-list (practiced during the intervention period) will consist of 12 semantically related words (e.g., birds). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to recall each list, and then participants will be asked to recall that list 20 minutes later (delayed recall). The investigators will compute the raw score of items correctly recalled (delayed recall) and transform to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.

  Before intervention, immediately after intervention and 1 month post intervention

• Change in auditory recall accuracy based on the sum of words recalled in Trials 1-5 of semantically unrelated - trained word-lists

  Each trained word-list (practiced during the intervention period) will consist of 12 semantically unrelated words as in Rey Auditory-Verbal Learning Test (RAVLT). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to learn each list. The investigators will compute the raw score of items correctly recalled by summing all scores from Trial 1 to Trial 5 and transforming to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.

  Before intervention, immediately after intervention and 1 month post intervention

• Change in auditory delayed recall accuracy of semantically unrelated - trained word-lists

  Each trained word-list (practiced during the intervention period) will consist of 12 semantically unrelated words (as in RAVLT). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to recall each list, and then participants will be asked to recall that list 20 minutes later (delayed recall). The investigators will compute the raw score of items correctly recalled (delayed recall) and transform to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.

  Before intervention, immediately after intervention and 1 month post intervention

• Change in auditory recall accuracy based the sum of words recalled in Trials 1-5 of semantically related - untrained word-lists

  Each untrained word-list (not practiced during the intervention period) will consist of 12 semantically related words (e.g., birds). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to learn each list. The investigators will compute the raw score of items correctly recalled by summing all scores from Trial 1 to Trial 5 and transforming to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.

  Before intervention, immediately after intervention and 1 month post intervention

• Change in auditory delayed recall accuracy of semantically related - untrained word-lists

  Each untrained word-list (not practiced during the intervention period) will consist of 12 semantically related words (e.g., birds). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to recall each list, and then participants will be asked to recall that list 20 minutes later (delayed recall). The investigators will compute the raw score of items correctly recalled (delayed recall) and transform to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.

  Before intervention, immediately after intervention and 1 month post intervention

• Change in auditory recall accuracy based on the sum of words recalled in Trials 1-5 of semantically unrelated - untrained word-lists

  Each untrained word-list (not practiced during the intervention period) will consist of 12 semantically unrelated words (as in RAVLT). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to learn each list. The investigators will compute the raw score of items correctly recalled by summing all scores from Trial 1 to Trial 5 and transforming to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.

  Before intervention, immediately after intervention and 1 month post intervention

• Change in auditory delayed recall accuracy of semantically unrelated - untrained word-lists

  Each untrained word-list (not practiced during the intervention period) will consist of 12 semantically unrelated words (as in RAVLT). Word lists will be constructed using psycholinguistic databases. There will be 5 Trials to recall each list, and then participants will be asked to recall that list 20 minutes later (delayed recall). The investigators will compute the raw score of items correctly recalled (delayed recall) and transform to percent correct (range: 0-100%) at each time point of the study. Increase in scores is considered a benefit.

  Before intervention, immediately after intervention and 1 month post intervention

Secondary Outcomes (21)

• Change in Rey Auditory-Verbal Learning Test (RAVLT) score

  Before intervention, immediately after intervention and 1 month post intervention

• Change in Mini Mental State Examination (MMSE)

  Before intervention, immediately after intervention and 1 month post intervention

• Change in Mnemonic Similarity Task (MST) score

  Before intervention, immediately after intervention and 1 month post intervention

• Change in word repetition score

  Before intervention, immediately after intervention and 1 month post intervention

• Change in non-word repetition score

  Before intervention, immediately after intervention and 1 month post intervention

Study Arms (1)

Personalized closed-loop tES treatment + Cognitive Interventions

EXPERIMENTAL

Participants will receive personalized, closed-loop active tES for 3 weeks. Active tES will be administered for 20 minutes. Cognitive training exercises will be administered concurrently with the tES and will take approximately 30 minutes to complete.

Device: Active tES; Behavioral: Cognitive Interventions

Interventions

Active tES DEVICE

This three-week, closed-loop program integrates personalized tES with computerized cognitive training to drive neuroplasticity. Following baseline electroencephalogram (EEG) mapping, participants undergo daily 30-minute sessions consisting of four "loops." Each loop begins with an AI-analyzed EEG to calibrate stimulation parameters, followed by 5-minute stimulation periods.

Personalized closed-loop tES treatment + Cognitive Interventions

Cognitive Interventions BEHAVIORAL

In between tES treatment loops, the participants will be asked to complete cognitive exercises. By pairing real-time brain modulation with targeted executive function exercises, the intervention aims to improve language skills and clinical outcomes through precise, data-driven cortical targeting.

Personalized closed-loop tES treatment + Cognitive Interventions

Eligibility Criteria

• Age: 45 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Must be between 45-85 years of age.
• Must be right-handed.
• Must be proficient in English.
• Must have a minimum of high-school education.
• Must be diagnosed as lvPPA with AD biomarkers. Other possible diagnosis for the 'aphasic AD' variant would be MCI or 'possible AD' according to 2011 guidelines with AD biomarkers (CSF or positron emission tomography (PET) amyloid-beta or fluorodeoxyglucose (FDG)-positron emission tomography (PET) with uni-hemispheric atrophy).
• Participants will be diagnosed from PPA and early dementias clinics at Johns Hopkins University or other specialized centers in US using current consensus criteria. Diagnosis will be based on neuropsychological testing, language testing (most commonly the Western Aphasia Battery), MRI and clinical assessment. The investigators will also use two new variant classification tests the investigators have developed at the lab which discriminate PPA variants with great accuracy (above 80%): a spelling test and a speech production test (i.e., Cookie Theft picture description task).

You may not qualify if:

• People with previous neurological disease including vascular dementia (e.g., stroke, developmental dyslexia, dysgraphia or attentional deficit).
• People with hearing loss (\> 25 decibel, using audiometric hearing screen).
• People with uncorrected visual acuity loss.
• People with advanced dementia or severe language impairments (MMSE \<15, or Montreal Cognitive Assessment \<10, or language Frontotemporal Dementia-specific Clinical Dementia Rating (FTD-CDR) =3).
• 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.

Sponsors & Collaborators

• Johns Hopkins University: lead
• Mackler-Goding Foundation: collaborator

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

Study Officials

• Kyrana Tsapkini, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: March 30, 2026
• First Posted: April 6, 2026
• Study Start (Estimated): June 1, 2026
• Primary Completion (Estimated): August 1, 2026
• Study Completion (Estimated): August 1, 2026
• Last Updated: May 8, 2026

Record last verified: 2026-05

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)