Treating Primary Progressive Aphasia (PPA) Using tDCS

NCT ID: NCT04566731

Last Updated: 2025-11-13

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: NA
• Total Enrollment: 23 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2020-12-01
• Study Completion Date: 2024-07-01

Brief Summary

This is a double-blind, sham-controlled, crossover study in which subjects with the non-fluent/agrammatic and semantic variants of primary progressive aphasia (naPPA and svPPA, respectively) will undergo language testing and structural and functional brain imaging before and after receiving 10 semi-consecutive daily sessions of real or sham transcranial direct current stimulation (tDCS) paired with modified constraint-induced language therapy (mCILT). Language testing and brain imaging will be repeated immediately after completion of and up-to 24 weeks following completion of treatment. The investigators will examine changes in language performance induced by tDCS + mCILT compared to sham 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.

Detailed Description

The central framework for the project is a double-blind, sham-controlled, crossover study in which subjects with the non-fluent/agrammatic and semantic variants of primary progressive aphasia (naPPA and svPPA, respectively) will undergo language testing and structural and functional brain imaging before and after receiving 10 semi-consecutive daily sessions of real or sham transcranial direct current stimulation (tDCS) paired with modified constraint-induced language therapy (mCILT). Language testing and brain imaging will be repeated immediately after completion of and up-to 24 weeks following completion of treatment.

Subjects with naPPA and svPPA will be randomized to one of two study arms: tDCS+mCILT or sham stimulation+mCILT paired with pre- and post-stimulation imaging and behavioral measures. Equal numbers of subjects with naPPA and svPPA will be randomized to the tDCS + mCILT and sham + mCILT study arms. The study is double-blinded, in that neither the subject nor the study personnel administering tDCS or sham stimulation will know which arm of the study the subject has been randomized into. Study coordinators will administer tDCS by entering a pre-determined code that has been programmed into the device by another member of the study team. Data will be digitally audio-recorded and analyzed off-line, such that study team members performing data coding and analysis will likewise be blinded to the treatment condition of each subject.

Subject participation in this protocol will occur during 36 planned visits that will span approximately 12 months. The events of the study visits are described below:

VISIT 1:

Informed consent and screening

VISIT 2:

Baseline MRI

VISIT 3 & 4:

Baseline language assessment

VISITS 5-14:

tDCS+mCILT OR sham stimulation+mCILT, depending on the study arm to which they had been randomized.

VISIT 15 & 16:

Follow-up language assessment Follow-up MRI

VISIT 17:

6-Week follow-up language assessment

VISIT 18 & 19:

12-week follow-up language assessment 12-week follow-up MRI

**CROSSOVER**

VISIT 20:

Crossover baseline language assessment

VISITS 21-30:

tDCS+mCILT or sham stimulation+mCILT

VISIT 31 & 32:

Follow-up language assessment Follow-up MRI

VISIT 33:

6 Week follow-up language assessment

VISIT 34 & 35:

12-week follow-up language assessment 12-week follow-up MRI

VISIT 36:

24 week follow-up language assessment

Conditions

Primary Progressive Aphasia

Keywords

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

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: CROSSOVER
• Primary Study Purpose: TREATMENT
• Blinding Strategy: TRIPLE

Study Groups

tDCS + CILT

Participants will undergo 10 daily sessions (Monday-Friday, x2 weeks) of tDCS for 20 minutes using a montage in which an anode (1.5 mA) is placed over F7 (left frontotemporal lobe) and the cathode will be place on O1 (left occipital) using the 10-20 EEG mapping system. Subjects will participate in a modified constraint-induced language therapy.

Group Type: ACTIVE_COMPARATOR

Transcranial Direct Current Stimulation (tDCS)

Intervention Type: DEVICE

tDCS is a type of non-invasive brain stimulation in which small electrical currents are applied to the scalp via 2 electrodes. The current, 1.5 mA, is approximately of the same intensity as the current provided by a 9-volt battery. To deliver the current, electrodes that are placed in saline soaked sponges. They will be attached to the left side of your head; they will be held in place with an elastic cap. For both real and sham stimulation the electrodes will be placed on the scalp.

Modified Contraint-Induced Language Therapy (mCILT)

Intervention Type: 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.

Sham tDCS + CILT

Participants will undergo 10 daily sessions (Monday-Friday, x2 weeks) of sham tDCS for 20 minutes using a montage in which an anode is placed of F7 and cathose is placed over O1. Subjects will participate in a modified constraint-induced language therapy,

Group Type: SHAM_COMPARATOR

Sham tDCS

Intervention Type: DEVICE

tDCS is a type of non-invasive brain stimulation in which small electrical currents are applied to the scalp via 2 electrodes. During sham stimulation, the current, 1.5 mA, will be delivered for a short amount of time and then turn-off. To deliver the current, electrodes that are placed in saline soaked sponges. They will be attached to the left side of your head; they will be held in place with an elastic cap. For both real and sham stimulation the electrodes will be placed on the scalp. Most people cannot tell the difference between real and sham stimulation.

Modified Contraint-Induced Language Therapy (mCILT)

Intervention Type: 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.

Interventions

Transcranial Direct Current Stimulation (tDCS)

tDCS is a type of non-invasive brain stimulation in which small electrical currents are applied to the scalp via 2 electrodes. The current, 1.5 mA, is approximately of the same intensity as the current provided by a 9-volt battery. To deliver the current, electrodes that are placed in saline soaked sponges. They will be attached to the left side of your head; they will be held in place with an elastic cap. For both real and sham stimulation the electrodes will be placed on the scalp.

Intervention Type: DEVICE

Sham tDCS

tDCS is a type of non-invasive brain stimulation in which small electrical currents are applied to the scalp via 2 electrodes. During sham stimulation, the current, 1.5 mA, will be delivered for a short amount of time and then turn-off. To deliver the current, electrodes that are placed in saline soaked sponges. They will be attached to the left side of your head; they will be held in place with an elastic cap. For both real and sham stimulation the electrodes will be placed on the scalp. Most people cannot tell the difference between real and sham stimulation.

Intervention Type: DEVICE

Modified Contraint-Induced Language Therapy (mCILT)

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.

Intervention Type: BEHAVIORAL

Eligibility Criteria

Inclusion Criteria

• Presence of aphasia attributable to the semantic variant (svPPA) or non- fluent/agrammatic variant (naPPA) of Primary Progressive Aphasia.
• Must be a native English speaker

Exclusion Criteria

• History of seizures or unexplained loss of consciousness
• Subjects with metallic objects in the face or head other than dental apparatus such as braces, fillings, and implants.
• Subjects with Pacemakers or ICDs.
• Subjects with previous craniotomy or any breach in the skull
• Subjects with a history of other neurological disorder (stroke, TBI, Parkinson)
• Subjects with a history of small vessel disease

• Minimum Eligible Age: 45 Years
• Maximum Eligible Age: 80 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University of Pennsylvania

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Roy Hamilton, MS

Role: PRINCIPAL_INVESTIGATOR

University of Pennsylvania

Locations

University of Pennsylvania

Philadelphia, Pennsylvania, United States

Countries

United States

Provided Documents

Document Type: Study Protocol and Statistical Analysis Plan

View Document

Other Identifiers

843286

Identifier Type: -

Identifier Source: org_study_id