Transcranial Direct Current Stimulation in the Treatment of Primary Progressive Aphasia

NCT05386394 | Recruiting Phase 2 DMC FDA Device

• 2 other identifiers: IRB003266811R01AG075111
• Study Type: interventional
• Target: 180
• Locations: 2 countries
• Sites: 3

Brief Summary

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.

Conditions

Primary Progressive Aphasia; Logopenic Progressive Aphasia; Non-Fluent Primary Progressive Aphasia

Keywords

transcranial direct current stimulation; language treatment; primary progressive aphasia

Outcome Measures

Primary Outcomes (4)

• 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.

  Baseline and Immediate follow-up of 3-week intervention period

• 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.

  Baseline and Immediate follow-up of 3-week intervention period

• 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.

  Baseline and 3 months post intervention

• 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.

  Baseline and 3 months post intervention

Secondary Outcomes (3)

• Change in Untrained Naming Items (phonemic accuracy)

  Baseline and 3 months post intervention

• Change in Untrained Naming Items (letter accuracy)

  Baseline and 3 months post intervention

• Change in functional connectivity of select brain regions (z-correlations)

  Immediate follow-up of 3-week intervention period and 3-month follow-up

Other Outcomes (17)

• Change in volumetric measurements of select brain regions

  Immediate follow-up of 3-week intervention period and 3-month follow-up

• Change in location of white matter tracts of select brain regions

  Immediate follow-up of 3-week intervention period and 3-month follow-up

• Change in anisotropy of white matter tracts of select brain regions

  Immediate follow-up of 3-week intervention period and 3-month follow-up

Study Arms (2)

Active tDCS + Language Therapy first

EXPERIMENTAL

Active tDCS will be applied at the beginning of 45 minutes language therapy session and will last for 20 minutes.

Device: Active tDCS + Language Therapy; Device: Sham tDCS + Language Therapy

Sham tDCS + Language Therapy first

SHAM COMPARATOR

Sham tDCS will be applied at the beginning of 45 minutes language therapy session.

Device: Active tDCS + Language Therapy; Device: Sham tDCS + Language Therapy

Interventions

Active tDCS + Language Therapy DEVICE

Active 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.

Active tDCS + Language Therapy first; Sham tDCS + Language Therapy first

Sham tDCS + Language Therapy DEVICE

During 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.

Active tDCS + Language Therapy first; Sham tDCS + Language Therapy first

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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
• A medically unstable cardiopulmonary or metabolic disorder
• Individuals with pacemakers or implantable cardiac defibrillators
• Terminal illness associated with survival of less than 12 months
• Major active psychiatric illness that may interfere with required study procedures or treatments, as determined by the enrolling physician
• Current abuse of alcohol or drugs, prescription or otherwise
• Participant in another drug, device, or biologics trial within 30 days prior to enrollment
• Nursing a child, pregnant, or intending to become pregnant during the study
• Left-handedness
• History of spontaneous or partial complex seizures or unexplained loss of consciousness within 6 months of enrollment
• Subjects with metallic objects in the face or head other than dental apparatus, such as braces, fillings, or implants
• Subjects with previous craniotomy or any breach in the skull

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institute on Aging (NIA): collaborator

Study Sites (3)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

RECRUITING

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

RECRUITING

Baycrest Centre for Geriatric Care

Toronto, Ontario, M6A 2E1, Canada

RECRUITING

Related Publications (9)

• Tsapkini K, Frangakis C, Gomez Y, Davis C, Hillis AE. Augmentation of spelling therapy with transcranial direct current stimulation in primary progressive aphasia: Preliminary results and challenges. Aphasiology. 2014;28(8-9):1112-1130. doi: 10.1080/02687038.2014.930410.

  PMID: 26097278 BACKGROUND

• Roncero C, Kniefel H, Service E, Thiel A, Probst S, Chertkow H. Inferior parietal transcranial direct current stimulation with training improves cognition in anomic Alzheimer's disease and frontotemporal dementia. Alzheimers Dement (N Y). 2017 Mar 24;3(2):247-253. doi: 10.1016/j.trci.2017.03.003. eCollection 2017 Jun.

  PMID: 29067331 BACKGROUND

• McConathey EM, White NC, Gervits F, Ash S, Coslett HB, Grossman M, Hamilton RH. Baseline Performance Predicts tDCS-Mediated Improvements in Language Symptoms in Primary Progressive Aphasia. Front Hum Neurosci. 2017 Jun 30;11:347. doi: 10.3389/fnhum.2017.00347. eCollection 2017.

  PMID: 28713256 BACKGROUND

• Gervits F, Ash S, Coslett HB, Rascovsky K, Grossman M, Hamilton R. Transcranial direct current stimulation for the treatment of primary progressive aphasia: An open-label pilot study. Brain Lang. 2016 Nov;162:35-41. doi: 10.1016/j.bandl.2016.05.007. Epub 2016 Aug 12.

  PMID: 27522537 BACKGROUND

• Roncero C, Service E, De Caro M, Popov A, Thiel A, Probst S, Chertkow H. Maximizing the Treatment Benefit of tDCS in Neurodegenerative Anomia. Front Neurosci. 2019 Nov 22;13:1231. doi: 10.3389/fnins.2019.01231. eCollection 2019.

  PMID: 31824242 BACKGROUND

• Tsapkini K, Webster KT, Ficek BN, Desmond JE, Onyike CU, Rapp B, Frangakis CE, Hillis AE. Electrical brain stimulation in different variants of primary progressive aphasia: A randomized clinical trial. Alzheimers Dement (N Y). 2018 Sep 5;4:461-472. doi: 10.1016/j.trci.2018.08.002. eCollection 2018.

  PMID: 30258975 BACKGROUND

• Boyle M. Semantic feature analysis treatment for aphasic word retrieval impairments: what's in a name? Top Stroke Rehabil. 2010 Nov-Dec;17(6):411-22. doi: 10.1310/tsr1706-411.

  PMID: 21239365 BACKGROUND

• Rapp B, Glucroft B. The benefits and protective effects of behavioural treatment for dysgraphia in a case of primary progressive aphasia. Aphasiology. 2009 Feb 1;23(2):236-265. doi: 10.1080/02687030801943054.

  PMID: 21603153 BACKGROUND

• Homan RW. The 10-20 electrode system and cerebral location. American Journal of EEG Technology. 1988;28(4):269-279.

  BACKGROUND

MeSH Terms

Conditions

Aphasia, Primary Progressive; Primary Progressive Nonfluent Aphasia

Interventions

Language Therapy

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Aphasia; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Frontotemporal Lobar Degeneration; TDP-43 Proteinopathies; Neurodegenerative Diseases; Proteostasis Deficiencies; Metabolic Diseases; Nutritional and Metabolic Diseases

Intervention Hierarchy (Ancestors)

Rehabilitation of Speech and Language Disorders; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics

Study Officials

• Kyrana Tsapkini, PhD.

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Kelly Eun, B.S.

CONTACT

(410) 929 - 0279; krmeun@jhmi.edu

Kyrana Tsapkini, PhD.

CONTACT

410-736-2940; tsapkini@jhmi.edu

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Model Details: This is a crossover design of tDCS + behavioral language therapy that crossovers to sham + behavioral language therapy in Arm 1, and sham + behavioral language therapy that crossovers to tDCS + behavioral language therapy in Arm 2.

Study Record Dates

• First Submitted: May 13, 2022
• First Posted: May 23, 2022
• Study Start: February 13, 2024
• Primary Completion (Estimated): February 1, 2028
• Study Completion (Estimated): February 1, 2028
• Last Updated: May 5, 2026

Record last verified: 2026-04

Locations

CA (1); US (2)