Clinical Trial: tDCS Intervention in Primary Progressive Aphasia

Study Status: Recruiting
Recruit Status: Recruiting
Study Type: Interventional

Official Title: Effects of Transcranial Direct Current Stimulation (tDCS) in Spoken and Written Production in Primary Progressive Aphasia (PPA)

Brief Summary: Primary progressive aphasia (PPA) is a neurodegenerative disease that affects first and foremost language abilities. Mild cognitive impairment (MCI) is slowly progressive decline in a single domain of cognition (e.g. language) not attributable to motor or sensory loss, without impediment of social or occupational function. MCI can be an early sign of neurodegenerative disease, or can be due to normal aging. When language is the prominent affected domain in MCI, the person may later meet criteria for PPA or may progress to the clinical syndrome of Alzheimer's dementia. Spelling, naming, and working memory (e.g. repetition) are among the language abilities affected early in the course of PPA or language-centered MCI, and different variants have distinct deficits in these domains. This research project investigates the behavioral and neuromodulatory effects of transcranial direct current stimulation (tDCS) during language therapy in PPA participants over time. Anodal tDCS targeting the left inferior frontal gyrus (IFG) administered in combination with language therapy is expected to be more beneficial when compared to language therapy alone. It will 1) improve language performance or decrease rate of decline, 2) have better-sustained effects at 2 weeks and 2 months post-treatment, and 3) produce generalization to untrained language items and some other cognitive functions. Resting-state fMRI, diffusion tensor imaging (DTI), and volumetric data are also collected to investigate changes in functional brain connectivity associated with tDCS in individuals with PPA. A better understanding of the therapeutic and neuromodulatory mechanisms of tDCS as an adjunct to language therapy in PPA may have a significant impact on the development of effective therapies for PPA and MCI, and may offer insight into ways of impeding neurodegeneration that may improve patients' quality of life, as well as extend their ability to work and manage their affairs.

Detailed Summary:

A. Evaluation Tasks

Language Tasks:

Participants will be administered baseline language and cognitive tasks, including 1 or more of the following, depending on their residual language and cognitive skills:

a) writing to dictation b) oral spelling c) oral and written naming of pictures d) word-picture matching f) written and oral picture description g) digit span h) spatial span i) verbal learning j) grammatical sentence production k) oral word repetition l) sentence comprehension

Quality of Life questionnaires:

Participants will be administered standardized and non-standardized quality-of-life questionnaires before, after, and at follow-up intervals of each experimental period. The purpose of these questionnaires is to assess whether the proposed interventions have affected participants' well-being and the general quality of their life.

B. Spoken and Written Word Production Therapy Interventions

Individuals with PPA will receive spoken and written word production intervention tailored to their degree of deficit. Two interventions (basic and advanced) will be implemented, treating the main lexical retrieval deficits in PPA, in oral and written modalities. The goal of the combined interventions is to promote interaction between phonological and orthographic representations and processes in the remediation of lexical retrieval deficits that are prominent in all PPA subtypes.

C. Assessment of Language Therapy Tasks:

Follow-up assessment will probe all sets of trained phoneme-grapheme
Sponsor: Johns Hopkins University

Current Primary Outcome:

• Change in oral naming (trained items) [ Time Frame: 35 weeks ]
  We will investigate any changes in performance from pre- to post-treatment levels of change in % accuracy in trained items.
• Change in written naming (trained items) [ Time Frame: 35 weeks ]
  We will investigate any changes in performance from pre- to post-treatment levels of change in % accuracy in trained items.
• Change in oral naming (untrained items) [ Time Frame: 35 weeks ]
  We will investigate any changes in performance from pre- to post-treatment levels of change in % accuracy in untrained items.
• Change in written naming (untrained items) [ Time Frame: 35 weeks ]
  We will investigate any changes in performance from pre- to post-treatment levels of change in % accuracy in untrained items.

Original Primary Outcome: Same as current

Current Secondary Outcome:

• Change in other language and cognitive task performances (global cognitive changes) [ Time Frame: 35 weeks ]
  Secondary outcome variables will be generalization of the improvement induced by the stimulation of the IFG in other language and cognitive functions with the same neural substrates.
• Changes in functional connectivity [ Time Frame: 35 weeks ]
  Using rsfMRI, DTI, and volumetric imaging, we will investigate whether tDCS intervention will result in different changes in connectivity between the targeted area and other nodes in the "language network," also controlling for the effect of gray and white matter volume loss as covariates.

Original Secondary Outcome: Same as current

Information By: Johns Hopkins University

Dates:
Date Received: November 11, 2015
Date Started: April 2013
Date Completion: May 2020
Last Updated: May 4, 2016
Last Verified: May 2016