Rehabilitating and Decelerating Language Loss in Primary Progressive Aphasia With tDCS Plus Language Therapy

Rehabilitating and Decelerating Language Loss in Primary Progressive Aphasia With Transcranial Direct Current Stimulation (tDCS) Plus Language Therapy

People with Primary Progressive Aphasia (PPA) are is a debilitating disorder characterized by the gradual loss of language functioning, even though cognitive functioning is relatively well preserved until the advanced stages of the disease. There are very few evidence-based treatment options available. This study investigates the behavioral and neural effects of multiple consecutive tDCS sessions paired with language therapy targeting verbs in sentences with individuals with PPA.

Study Overview

• Status: Completed
• Conditions: Primary Progressive Aphasia; PPA
• Intervention / Treatment: Device: Sham tDCS plus Speech-Language Therapy; Device: Active tDCS plus Speech-Language Therapy

Detailed Description

Primary Progressive Aphasia (PPA) is a debilitating disorder characterized by the gradual loss of language functioning, even though cognitive functioning is relatively well preserved until the advanced stages of the disease. There are three main PPA variants classified based on the pattern of language impairments and areas of atrophy, but anomia is present across all variants in the earliest stages. While there is a significant amount of research investigating multiple treatment approaches for individuals with aphasia resulting from stroke, individuals with PPA have far fewer treatment options to choose from. Recently, a growing body of literature of treatment in stroke-based aphasia have found promising results for pairing traditional language therapy with non-invasive neurostimulation via transcranial direct current stimulation (tDCS). The small amount of studies of the effects of tDCS applied to left inferior frontal gyrus (IFG) in PPA also yield promising results that show tDCS can enhance generalization to untreated structures. Research in stroke-based aphasia has also shown that language outcomes significantly improve when participants are treated with more complex language stimuli, because this treatment approach results in enhanced generalization. For example, therapy that has participants build sentences around verbs has been found to improve word-level verb and noun naming. The current proposal aims to investigate whether combining the benefits of tDCS while providing verb retrieval therapy that uses sentence building to improve word-level retrieval deficits, will enhance word retrieval deficits in PPA and slow the loss of language functioning. It is hypothesized that Furthermore, the proposed study will investigate the atrophy patterns at baseline, to determine which atrophy patterns are predictive of improved word retrieval. Specifically, this proposal aims: 1) to determine whether tDCS to left IFG coupled with therapy promoting verb retrieval within sentences improve noun and verb retrieval in treated and untreated items in individuals with PPA, and 2) To investigate which patterns of atrophy are predictive of maintenance and generalization of word-retrieval in individuals with PPA following tDCS+therapy vs. sham+therapy. This proposed research will allow the investigators to evaluate the potential benefits and sustainability of tDCS in PPA, the generalization of trained items to untrained items, as well as the deceleration of language loss.

• Study Type: Interventional
• Enrollment (Actual): 8
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Shannon M Sheppard, PhD; Phone Number: 410-502-6045; Email: sheppard@jhmi.edu
• Study Contact Backup: Name: Argye E Hillis, MD, MS; Phone Number: 410-614-2381; Email: argye@jhmi.edu

Study Locations

• United States
  • Maryland
    • Baltimore, Maryland, United States, 21287
      • Johns Hopkins School of Medicine

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 100 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

• Diagnosis of PPA, based on the PPA criteria and presence of naming deficits
• Capable of giving informed consent or indicating another to provide informed consent
• 18 years of age to 100 years of age..

Exclusion Criteria:

• Did not speak English before the age of five
• Less than 10 years of education
• Severe naming deficits
• Significant history of drug or alcohol abuse
• History of psychiatric or neurological problems affecting the brain (besides PPA)
• Has experienced seizures during the previous 12 months
• History of brain surgery or any metal in the head
• Uncorrected visual loss or hearing loss by self-report
• Use of medications that lower the seizure threshold (e.g., methylphenidate) or use of N-Methyl-D-aspartate (NMDA) receptor antagonists (e.g., memantine)
• Scalp sensitivity (per participant report)

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
Experimental: Active tDCS plus Speech-Language Therapy; Active tDCS will be applied at the beginning of 45min speech-language therapy session and will last for 20 min. Language therapy will be verb naming therapy in a sentence context. This will be followed by sham tDCS plus speech-language therapy after a 2 month washout period.	Device: Sham tDCS plus Speech-Language Therapy; Sham tDCS stimulation is provided to the left inferior frontal gyrus (IFG) using a tDCS device. Speech-language therapy will be verb naming therapy in a sentence context.; Device: Active tDCS plus Speech-Language Therapy; 1-2 milliamps (mA) of Anodal tDCS stimulation is induced between 5cm X5 cm saline soaked sponges where one sponge is placed on the left inferior frontal gyrus (IFG). The stimulation will be delivered at an intensity of 1-2 mA in a ramp-like fashion for a maximum of 20 minutes. Speech-language therapy will be verb naming therapy in a sentence context.; Other Names: Active tDCS and speech-therapy
Sham Comparator: Sham plus Speech-Language Therapy; Sham tDCS will be applied at the beginning of 45min speech-language therapy session. Language therapy will be oral and written naming. Language therapy will be verb naming therapy in a sentence context. This will be followed by active tDCS plus speech-language therapy after a 2 month washout period.	Device: Sham tDCS plus Speech-Language Therapy; Sham tDCS stimulation is provided to the left inferior frontal gyrus (IFG) using a tDCS device. Speech-language therapy will be verb naming therapy in a sentence context.; Device: Active tDCS plus Speech-Language Therapy; 1-2 milliamps (mA) of Anodal tDCS stimulation is induced between 5cm X5 cm saline soaked sponges where one sponge is placed on the left inferior frontal gyrus (IFG). The stimulation will be delivered at an intensity of 1-2 mA in a ramp-like fashion for a maximum of 20 minutes. Speech-language therapy will be verb naming therapy in a sentence context.; Other Names: Active tDCS and speech-therapy

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Accuracy of Naming Trained Verbs (0 to 15, Higher Scores Reflect Better Naming Abilities) as Assessed by Object and Action Naming Battery (OANB)	To determine whether tDCS + language therapy will improve naming performance of participants with Primary Progressive Aphasia more effectively than language therapy alone (the sham condition). The primary outcome variable will be trained verbs on the Object and Action Naming battery (OANBtrained). The OANB has 262 items, scored from 0 to 262, with higher scores on the OANB reflecting better naming abilities. The OANB includes 100 verbs (15 trained, 85 untrained) and 162 nouns.	Baseline, and 4-7 weeks after treatment begins

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Functional Communication Skills as Assessed by the Functional Assessment of Communication Skills for Adults (ASHA FACS)	The ASHA FACS will be administered pre-treatment and post-treatment to evaluate changes in functional communication skills. The ASHA FACS is used for measuring the functional communication of adults with speech, language, and cognitive communication disorders. The Communicative Independence Scale will be used, which is rated on a 7-point scale ranging from 1 "does not perform the behavior" to 7 "does perform the behavior". The scores on the Communicative Independence Scale range from a low score of 1 to a high score of 7. A higher score on this subscale indicates better ability to communicate independently.	Baseline, and 4-7 weeks after treatment begins
Change in Functional Communication Skills as Assessed by the Functional Assessment of Communication Skills for Adults (ASHA FACS)	The ASHA FACS will be administered pre- treatment and post treatment to evaluate changes in functional communication skills. The ASHA FACS is used for measuring the functional communication of adults with speech, language, and cognitive communication disorders. The Communicative Independence Scale will be used, which is rated on a 7-point scale ranging from 1 "does not perform the behavior" to 7 "does perform the behavior". The scores on the Communicative Independence Scale range from a low score of 1 to a high score of 7. A higher score on this subscale indicates better ability to communicate independently.	Baseline, and 2 months after treatment ends
Change in Accuracy of Naming Untrained Verbs (0 to 85, Higher Scores Reflect Better Naming Abilities) and Nouns (0 to 162, Higher Scores Reflect Better Naming Abilities) as Assessed by Object and Action Naming Battery	To determine whether tDCS + language therapy will improve naming performance of participants with Primary Progressive Aphasia more effectively than language therapy alone (the sham condition). The OANB has 262 items, scored from 0 to 262, with higher scores on the OANB reflecting better naming abilities. There are 100 verbs (15 trained, 85 untrained) on the OANB, and 162 nouns.	Baseline, and 4-7 weeks after treatment begins
Change in Accuracy of Naming Trained Verbs (0 to 15, Higher Scores Reflect Better Naming Abilities) as Assessed by Object and Action Naming Battery	To determine whether tDCS + language therapy will improve naming performance of participants with Primary Progressive Aphasia more effectively than language therapy alone (the sham condition). The OANB has 262 items, scored from 0 to 262, with higher scores on the OANB reflecting better naming abilities. There are 100 verbs (15 trained, 85 untrained) and 162 nouns on the OANB.	Baseline, and 2 months after treatment ends
Change in Accuracy of Naming Untrained Verbs (0 to 85, Higher Scores Reflect Better Naming Abilities) and Untrained Nouns (0 to 162, Higher Scores Reflect Better Naming Abilities) as Assessed by Object and Action Naming Battery	To determine whether tDCS + language therapy will improve naming performance of participants with Primary Progressive Aphasia more effectively than language therapy alone (the sham condition). The OANB has 262 items, scored from 0 to 262, with higher scores on the OANB reflecting better naming abilities. There are 100 verbs (15 trained, 85 untrained) on the OANB, and 162 nouns.	Baseline, and 2 months after treatment ends

Collaborators and Investigators

• Sponsor: Johns Hopkins University
• Investigators: Principal Investigator: Shannon M Sheppard, PhD, Johns Hopkins University

Study record dates

Study Major Dates

• Study Start (Actual): October 10, 2018
• Primary Completion (Actual): March 30, 2022
• Study Completion (Actual): March 30, 2022

Study Registration Dates

• First Submitted: October 31, 2018
• First Submitted That Met QC Criteria: October 31, 2018
• First Posted (Actual): November 2, 2018

Study Record Updates

• Last Update Posted (Actual): April 27, 2023
• Last Update Submitted That Met QC Criteria: April 25, 2023
• Last Verified: April 1, 2023

More Information

Terms related to this study

• Keywords: Dementia; Aphasia; Anomia; Frontotemporal Dementia; Neurocognitive Disorders; Language therapy
• 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: IRB00174879

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO
• IPD Plan Description: Upon completion of the projects and dissemination of primary study results, the de-identified analysis data files will be made available to the public, along with the final version of the study protocol, the data dictionary, and brief instructions ("read me" file). The public use data files and the accompanying documents will be made available through the National Technical Information Service (NTIS).

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.: Yes