- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT02606422
tDCS Intervention in Primary Progressive Aphasia
Effects of Transcranial Direct Current Stimulation (tDCS) in Spoken and Written Production in Primary Progressive Aphasia (PPA)
Study Overview
Status
Conditions
Intervention / Treatment
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 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 correspondences, words, or other stimuli (e.g. sentences) to identify whether or not the patient has retained knowledge of the trained items. Differences in baseline measures in pre- and post-therapy accuracy for phoneme-grapheme correspondences for each patient will be evaluated using the following: percentages of total number of points correct, arithmetic differences between percentage scores, and permutation tests (Pearson's chi-square test; Fisher's exact test).
C. HD-tDCS Methods:
Participants will take part in 10-15 consecutive training sessions (3-5 per week), separated by 2 months. Anodal HD-tDCS has typically been shown to up-regulate neuronal excitability and produce enhancement of behavioral performance. A Soterix-CT device will be delivering current at an intensity of 1-2 milliamps(mA) (estimated current density 0.04 mA/cm2; estimated total charge 0.048C/cm2) for a maximum of 20 minutes in the HD-tDCS groups and for a maximum of 30 seconds in the Sham group. For both interventions (HD-tDCS and Sham) the electrical current will be increased in a ramp-like fashion at the onset of the stimulation eliciting a transient tingling sensation on the scalp that usually disappears over seconds.
D. Imaging Methods:
Imaging will be performed at the beginning of enrollment, before and after each 12-to-15-day HD-tDCS treatment, and at follow-up intervals for up to 8 time points per individual on a 3T Philips system, and will consist of resting-state fMRI (rsfMRI), MPRAGE, and diffusion tensor imaging (DTI). Each scanning session will last approximately 1 hour.
E. Statistical Analyses:
In the within-subject crossover protocol, each participant will be administered three experimental conditions: Control (natural progression), IFG HD-tDCS+language (henceforth abbr. HD-tDCS treatment (word production) and sham HD-tDCS+language (henceforth abbr. sham treatment). To achieve an accurate estimate of degeneration and rate of decline in each participant at their particular stage of the disease progression, each participant will first be enrolled in the control condition (natural progression), such that for the first 12 weeks they will not receive any therapy. Then the participant will receive either the HD-tDCS treatment followed by sham, or vice versa. All analyses, behavioral and imaging, will be under the oversight of the study statisticians.
F. Study duration and number of study visits required of research participants.
Before any intervention, participants will be enrolled in a control condition for 12 weeks during which no therapy will be provided to enable us to assess their personal decline rate. After this period they will be randomly assigned to either sham or HD-tDCS experimental conditions. After 1-3 weeks of HD-tDCS application (3-5 sessions in a week, 10-15 sessions per stimulation site) there will be an interval of approximately 2 months and then we will implement the other two HD-tDCS conditions in a within-subject cross-over design. Participants will be followed up at 2-week and 2-month follow-up intervals.
G. Blinding, including justification for blinding or not blinding the trial, if applicable.
Participants will be blinded to the application of anodal or sham HD-tDCS. To achieve blinding, all participants will be fitted with the HD-tDCS electrodes placed over the left inferior frontal gyrus. The Soterix-CT device will be used for double-blinding purposes.
H. Justification of why participants will not receive routine care or will have current therapy stopped
Participation in this study will not disrupt any current care or therapy.
I. Justification for inclusion of a placebo or non-treatment group
All participants will undergo active and sham conditions, thus serving as their own control.
J. Definition of treatment failure or participant removal criteria
Participants will be removed from the study if they are unable to comply with task instructions or tolerate the HD-tDCS procedure.
K. Description of what happens to participants receiving therapy when the study ends or if a participant's participation in the study ends prematurely
When the study ends participants will continue to receive management with their neurologist as usual. If a patient's participation in the study ends prematurely s/he will still receive care as before. In sum, termination of the study or termination of participation in it will not affect the regular therapy he or she may be receiving.
L. Qualification of investigators:
The PI and co-investigators have extensive research and clinical experience with all study tasks: behavioral language therapy (including spelling, naming, and repetition therapy. The investigators have already published a tDCS study on the behavioral results for the improvement of spelling abilities.
Study Type
Enrollment (Estimated)
Phase
- Not Applicable
Contacts and Locations
Study Contact
- Name: Kyrana Tsapkini, PhD
- Phone Number: 4107362940
- Email: tsapkini@jhmi.edu
Study Contact Backup
- Name: Jessica Gallegos, B.S.
- Email: jgallegos@jhmi.edu
Study Locations
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Maryland
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Baltimore, Maryland, United States, 21204
- Recruiting
- Johns Hopkins Hospital
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Sub-Investigator:
- Argye Hillis, MD
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Contact:
- Kyrana Tsapkini, PhD
- Phone Number: 410-736-2940
- Email: tsapkini@jhmi.edu
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Principal Investigator:
- Kyrana Tsapkini, PhD
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Contact:
- Jessica Gallegos, B.S.
- Email: jgallegos@jhmi.edu
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Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Description
Inclusion Criteria:
- Must be clinically diagnosed with semantic variant PPA (svPPA), non-fluent variant PPA (nfvPPA), or logopenic variant PPA (lvPPA), unclassifiable PPA, or MCI. 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 speakers 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.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Crossover Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Active HD-tDCS plus Speech-Language Therapy
Active HD-tDCS will be applied at the beginning of 45min speech-language therapy session and will last for 20 min.
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Stimulation will be delivered by a battery-driven constant current stimulator.
The electrical current will be administered to a pre-specified region of the brain (inferior frontal gyrus).
The stimulation will be delivered at an intensity of 2mA (estimated current density 0.04 mA/cm2; estimated total charge 0.048C/cm2) in a ramp-like fashion for a maximum of 20 minutes.
Speech-language therapy will be oral and written naming.
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Sham Comparator: Sham plus Speech-Language Therapy
Sham HD-tDCS will be applied at the beginning of 45min speech-language therapy session.
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Speech-language therapy will be administered during sham stimulation.
Current will be administered in a ramp-line fashion but after the ramping the intensity will drop to 0 mA.
Speech-language therapy will be oral and written naming.
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What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in oral naming (trained items)
Time Frame: 35 weeks
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We will investigate any changes in performance from pre- to post-treatment levels of change in % accuracy in trained items.
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35 weeks
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Change in written naming (trained items)
Time Frame: 35 weeks
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We will investigate any changes in performance from pre- to post-treatment levels of change in % accuracy in trained items.
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35 weeks
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Change in oral naming (untrained items)
Time Frame: 35 weeks
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We will investigate any changes in performance from pre- to post-treatment levels of change in % accuracy in untrained items.
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35 weeks
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Change in written naming (untrained items)
Time Frame: 35 weeks
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We will investigate any changes in performance from pre- to post-treatment levels of change in % accuracy in untrained items.
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35 weeks
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Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Change in other language and cognitive task performances (global cognitive changes)
Time Frame: 35 weeks
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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.
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35 weeks
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Changes in functional connectivity
Time Frame: 35 weeks
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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.
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35 weeks
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Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Kyrana Tsapkini, PhD, Johns Hopkins University
Publications and helpful links
General Publications
- Tippett DC, Hillis AE, Tsapkini K. Treatment of Primary Progressive Aphasia. Curr Treat Options Neurol. 2015 Aug;17(8):362. doi: 10.1007/s11940-015-0362-5.
- Tsapkini K, Frangakis C, Gomez Y, Davis C, Hillis AE. Augmentation of spelling therapy with transcranial direct current stimulation in primary progressive aphasia: Preliminary results and challenges. Aphasiology. 2014;28(8-9):1112-1130. doi: 10.1080/02687038.2014.930410.
- Herrmann O, Ficek B, Webster KT, Frangakis C, Spira AP, Tsapkini K. Sleep as a predictor of tDCS and language therapy outcomes. Sleep. 2022 Mar 14;45(3):zsab275. doi: 10.1093/sleep/zsab275.
- Tao Y, Ficek B, Rapp B, Tsapkini K. Different patterns of functional network reorganization across the variants of primary progressive aphasia: a graph-theoretic analysis. Neurobiol Aging. 2020 Dec;96:184-196. doi: 10.1016/j.neurobiolaging.2020.09.007. Epub 2020 Sep 8.
Helpful Links
Study record dates
Study Major Dates
Study Start
Primary Completion (Estimated)
Study Completion (Estimated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimated)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
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
- NA_00071337
- R01DC014475 (U.S. NIH Grant/Contract)
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Primary Progressive Aphasia
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Massachusetts General HospitalCompletedLogopenic Variant Primary Progressive Aphasia | Non-Fluent Primary Progressive AphasiaUnited States
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Johns Hopkins UniversityCompletedPrimary Progressive Aphasia | PPAUnited States
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Casa Colina Hospital and Centers for HealthcareCompleted
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The University of Texas at DallasCompleted
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