Treating Primary Progressive Aphasia (PPA) Using tDCS

Using Transcranial Direct Current Stimulation to Reveal Mechanisms of Language Loss and to Treat Progressive Aphasia Associated With FTD and Related Dementias

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.

Study Overview

• Status: Recruiting
• Conditions: Primary Progressive Aphasia
• Intervention / Treatment: Device: Transcranial Direct Current Stimulation (tDCS); Behavioral: Modified Contraint-Induced Language Therapy (mCILT); Device: Sham tDCS

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

• Study Type: Interventional
• Enrollment (Estimated): 62
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Daniela Sacchetti, MS; Phone Number: 215-572-8485; Email: danielas@pennmedicine.upenn.edu
• Study Contact Backup: Name: Megan Hoffman, BS; Phone Number: 215-573-4336; Email: megan.hoffman1@pennmedicine.upenn.edu

Study Locations

• United States
  • Pennsylvania
    • Philadelphia, Pennsylvania, United States, 19104
      • Recruiting
      • University of Pennsylvania
      • Contact: Daniela Sacchetti, MS

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 45 years to 80 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Triple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 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.	Device: 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.; Behavioral: 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.
Sham Comparator: 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,	Behavioral: 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.; 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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Western Aphasia Battery (WAB)	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 to 24 weeks

Collaborators and Investigators

• Sponsor: University of Pennsylvania
• Investigators: Principal Investigator: Roy Hamilton, MS, University of Pennsylvania

Study record dates

Study Major Dates

• Study Start (Actual): December 1, 2020
• Primary Completion (Estimated): July 1, 2024
• Study Completion (Estimated): July 1, 2024

Study Registration Dates

• First Submitted: August 31, 2020
• First Submitted That Met QC Criteria: September 25, 2020
• First Posted (Actual): September 28, 2020

Study Record Updates

• Last Update Posted (Actual): October 25, 2023
• Last Update Submitted That Met QC Criteria: October 24, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Keywords: speech therapy; non-invasive brain stimulation; transcranial direct current stimulation (tDCS)
• Additional Relevant MeSH Terms: Mental Disorders; Metabolic Diseases; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurologic Manifestations; Neurobehavioral Manifestations; Neurocognitive Disorders; Neurodegenerative Diseases; TDP-43 Proteinopathies; Proteostasis Deficiencies; Dementia; Language Disorders; Communication Disorders; Speech Disorders; Frontotemporal Lobar Degeneration; Aphasia; Frontotemporal Dementia; Aphasia, Primary Progressive; Pick Disease of the Brain
• Other Study ID Numbers: 843286

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: Yes
• product manufactured in and exported from the U.S.: No