Effects of Transcranial Direct Current Stimulation in Primary Progressive Aphasia (PPA)
Trial Snapshot
- Phase
- Not Applicable
- Status
- Withdrawn
- Sponsor
- Johns Hopkins University
- Enrollment
- 60
- Locations
- 1
- Primary Endpoint
- Change in segmental duration of vowels of trained words
Study Overview
Brief Summary
Primary progressive aphasia (PPA) is a neurodegenerative disease that affects first and foremost language abilities. There are three different variants of PPA, each a relatively distinct speech and language profile. For individuals with non-fluent variant PPA (nfvPPA), a core symptom is apraxia of speech (AOS), which is defined as an oral motor speech disorder. Such a disorder inhibits one's ability to translate speech plans into motor plans and results in longer segmental durations and reduced rate of syllabic production.
This research project investigates the behavioral and neuromodulatory effects of transcranial direct current stimulation (tDCS) during language therapy in participants with nfvPPA 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 (sham). The investigators believe tDCS during language therapy will 1) improve language performance or decrease rate of decline, 2) promote 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 nfvPPA may have a significant impact on the development of effective therapies for PPA, and may offer insight into ways of impeding neurodegeneration that may improve patients' quality of life, as well as extend patients' ability to work and manage patients' affairs.
Detailed Description
A. Evaluation Tasks
Language Tasks:
Participants will be administered baseline language and cognitive tasks, including 1 or more of the following, depending on participants' 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:
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Crossover
- Primary Purpose
- Treatment
- Masking
- Triple (Participant, Care Provider, Outcomes Assessor)
Eligibility Criteria
- Ages
- 50 Years to 90 Years (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •Must be clinically diagnosed with nfvPPA or unclassifiable PPA. Diagnosis will be based on neuropsychological testing, language testing (most commonly the Western Aphasia Battery), MRI and clinical assessment.
- •Must be right-handed.
- •Must be speaker of English.
- •Must have at least 9th grade education.
Exclusion Criteria
- •Uncorrected visual or hearing impairment by self report.
- •Stroke/other premorbid neurological disorder affecting the brain.
- •Any other language-based learning disorder other than PPA.
- •Inability to follow directions for baseline tasks.
- •Western Aphasia Battery Aphasia Quotient (AQ) <30 (indicating severe language impairment).
- •Exclusion Criteria for MRI Participation:
- •Severe claustrophobia.
- •Cardiac pacemakers or ferromagnetic implants.
- •Pregnant women.
Arms & Interventions
Active tDCS plus Speech-Language Therapy first
Active tDCS will be applied at the beginning of 45 minutes speech-language therapy session and then participant will be switched to sham tDCS after a washout period.
Intervention: Active tDCS plus Speech-Language Therapy (Device)
Active tDCS plus Speech-Language Therapy first
Active tDCS will be applied at the beginning of 45 minutes speech-language therapy session and then participant will be switched to sham tDCS after a washout period.
Intervention: Sham plus Speech-Language Therapy (Device)
Sham plus Speech-Language Therapy first
Sham will be applied at the beginning of 45 minutes speech-language therapy session and then participant will be switched to an active tDCS after a washout period.
Intervention: Active tDCS plus Speech-Language Therapy (Device)
Sham plus Speech-Language Therapy first
Sham will be applied at the beginning of 45 minutes speech-language therapy session and then participant will be switched to an active tDCS after a washout period.
Intervention: Sham plus Speech-Language Therapy (Device)
Outcomes
Primary Outcomes
Change in segmental duration of vowels of trained words
Time Frame: Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention
Duration of vowels for trained words (practiced in therapy) will be measured in milliseconds (ms) via acoustic analyses. Investigators will compute the change in outcome over time: before intervention versus each time point after. Decrease in duration is considered a benefit.
Change in speech fluency on untrained words
Time Frame: Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention
Speech fluency will be measured on untrained words (not practiced in therapy) using the mean log of sound duration collected via acoustic analyses. Investigators will compute the change in outcome over time: before intervention versus each time point after. Lower log duration indicates faster speech production. A decrease in sound duration is considered a benefit.
Change in segmental duration of vowels of untrained words
Time Frame: Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention
Duration of vowels for untrained words (not practiced in therapy) will be measured in milliseconds (ms) via acoustic analyses. Investigators will compute the change in outcome over time: before intervention versus each time point after. Decrease in duration is considered a benefit.
Change in segmental duration of consonants of trained words
Time Frame: Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention
Duration of consonants for trained words (practiced in therapy) will be measured in milliseconds (ms) via acoustic analyses. Investigators will compute the change in outcome over time: before intervention versus each time point after. Decrease in duration is considered a benefit.
Change in segmental duration of consonants of untrained words
Time Frame: Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention
Duration of consonants for untrained words (not practiced in therapy) will be measured in milliseconds (ms) via acoustic analyses. Investigators will compute the change in outcome over time: before intervention versus each time point after. Decrease in duration is considered a benefit.
Change in speech fluency on trained words
Time Frame: Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention
Speech fluency will be measured on trained words (practiced in therapy) using the mean log of sound duration collected via acoustic analyses. Investigators will compute the change in outcome over time: before intervention versus each time point after. Lower log duration indicates faster speech production. A decrease in sound duration is considered a benefit.
Secondary Outcomes
- Change in verbal fluency task score(Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention)
- Change in digit span forward score(Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention)
- Change in anisotropy of white matter tracts of select brain regions(Before intervention, immediately after intervention and 3 months post intervention)
- Change in syntactic comprehension as assessed by Subject-relative, Object-relative, Active, Passive (S.O.A.P.) Syntactic Battery(Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention)
- Change in oral naming of action as assessed by Hopkins Assessment of Naming Actions (HANA)(Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention)
- Change in location of white matter tracts of select brain regions(Before intervention, immediately after intervention and 3 months post intervention)
- Change in prosody/intonation of trained words(Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention)
- Change in semantic content of connected speech(Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention)
- Change in prosody/intonation of untrained words(Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention)
- Change in oral naming Boston Naming Test score(Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention)
- Change in digit span backward score(Before intervention, immediately after intervention, 1 month post intervention and 3 months post intervention)
- Change in volumetric measurements of select brain regions(Before intervention, immediately after intervention and 3 months post intervention)