Treating Primary Progressive Aphasia (PPA) Using High-definition tDCS

NCT04046991 | Completed Phase 2 DMC FDA Device

• 1 other identifier: 834650
• Study Type: interventional
• Target: 76
• Locations: 1 country
• Sites: 1

Brief Summary

This is a double-blind, sham-controlled, crossover study in which subjects with the non-fluent/agrammatic and logopenic variants of primary progressive aphasia (naPPA and lvPPA, respectively) will undergo language testing and structural and functional brain imaging before and after receiving 10 semi-consecutive daily sessions of real or sham high-definition transcranial direct current stimulation (HD-tDCS) paired with modified constraint-induced language therapy (mCILT). Language testing and brain imaging will be repeated immediately after completion of and 3 months following completion of treatment. The 3-month follow-up will be the primary endpoint. The investigators will examine changes in language performance induced by HD-tDCS + mCILT compared to sham HD-tDCS + mCILT. The investigators will also use network science to analyze brain imaging (fMRI) data to identify network properties associated with baseline PPA severity and tDCS-induced changes in performance. This study will combine knowledge gained from our behavioral, imaging, and network data in order to determine the relative degrees to which these properties predict whether persons with PPA will respond to intervention.

Conditions

Primary Progressive Aphasia

Keywords

non-invasive brain stimulation; transcranial direct current stimulation (tDCS); aphasia

Outcome Measures

Primary Outcomes (1)

• Change in Western Aphasia Battery Aphasia Quotient (WAB-AQ)

  The primary outcome measure will be the change in score on the WAB-AQ, a score assessing overall aphasia recovery. Scores can range from 0-100. 0-25 is very severe, 26-50 is severe, 51-75 is moderate, and 76-above is mild. A score of 93 or higher is considered recovered.

  Baseline, 2 weeks, 6 weeks, 12 weeks, 14 weeks, 18 weeks, 24 weeks

Study Arms (2)

HD-tDCS+mCILT

ACTIVE COMPARATOR

Participants will undergo 10 daily sessions (Monday-Friday, x2 weeks) of HD-tDCS for 20 minutes using a montage in which a central electrode (1.5mA) is placed over the left frontotemporal area and four surrounding cathodes (.375mA each). Subjects will participate in a modified constraint-induced language therapy.

Device: high-definition transcranial direct current stimulation; Behavioral: modified constraint-induced language therapy

Sham+mCILT

SHAM COMPARATOR

Participants will undergo 10 daily sessions (Monday-Friday, x2 weeks) of sham for 20 minutes using a montage in which a central electrode is placed over the left frontotemporal area and four surrounding cathodes. Subjects will participate in a modified constraint-induced language therapy,

Device: high-definition transcranial direct current stimulation; Behavioral: modified constraint-induced language therapy

Interventions

high-definition transcranial direct current stimulation DEVICE

High definition transcranial direct current stimulation (HD-tDCS) involves the application of low-intensity current through electrodes placed on the scalp. It is believed to elicit brain effects by producing incremental shifts in the resting membrane potential of large numbers of neurons, which alters neuronal firing rates and thus modulates patterns of brain activity in potentially behaviorally-relevant ways. HD-tDCS differs from conventional transcranial direct current stimulation (tDCS) because it employed smaller electrodes configured in such a way as to deliver more focal stimulation of the brain.

HD-tDCS+mCILT; Sham+mCILT

modified constraint-induced language therapy BEHAVIORAL

Modified constraint-induced language therapy (mCILT) is a behavioral language therapy that invokes use-dependent learning in communicative interactions by requiring spoken output and restricting use of alternative forms of communication, such as gestures, as a substitute for spoken output. Other key elements of CILT include massed practice of goal-directed speech and shaping of desired responses by increasing response demands as participants improve. MCILT differs from traditional constraint-induced language therapy (CILT) in three ways: 1) it will be done as an individual therapy with the examiner in the role of a communication partner; 2) treatment will be delivered in short sessions (1 hour rather than a more typical 3-4 hour session); 3) targeting nouns + semantically related verbs to generate noun + verb phrases in treatment, a modification that may be better suited to addressing syntactic structure.

HD-tDCS+mCILT; Sham+mCILT

Eligibility Criteria

• Age: 45 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Presence of aphasia attributable to nonfluent agrammatic PPA (naPPA) or logopenic variant PPA (lvPPA)
• High school education (or more)
• Must be able to understand the nature of the study, and give informed consent
• Native English speaker

You may not qualify if:

• Presence of additional neurological illness such as stroke or traumatic brain injury
• Diagnosis of epilepsy or reoccurening seizures
• Pacemaker or ICDs
• Craniotomy or skull breech
• Small vessel disease

Sponsors & Collaborators

• University of Pennsylvania: lead

Study Sites (1)

University of Pennsylvania

Philadelphia, Pennsylvania, 19104, United States

Location

MeSH Terms

Conditions

Aphasia, Primary Progressive; Aphasia

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders

Study Officials

• Roy H Hamilton, MD

  University of Pennsylvania

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 12, 2019
• First Posted: August 6, 2019
• Study Start: August 17, 2020
• Primary Completion: June 30, 2025
• Study Completion: June 30, 2025
• Last Updated: October 15, 2025

Record last verified: 2025-10

Locations

US (1)