tDCS Intervention in Primary Progressive Aphasia
Primary Purpose
Primary Progressive Aphasia, MCI, FTD
Status
Recruiting
Phase
Not Applicable
Locations
United States
Study Type
Interventional
Intervention
Active HD-tDCS plus Speech-Language Therapy
Sham plus Speech-Language Therapy
Sponsored by
About this trial
This is an interventional treatment trial for Primary Progressive Aphasia focused on measuring transcranial direct current stimulation (tDCS), neurodegeneration, language therapy, Primary Progressive Aphasia (PPA)
Eligibility Criteria
Inclusion Criteria:
- Must be clinically diagnosed with svPPA, nfvPPA or 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.
Sites / Locations
- Johns Hopkins HospitalRecruiting
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Sham Comparator
Arm Label
Active HD-tDCS plus Speech-Language Therapy
Sham plus Speech-Language Therapy
Arm Description
Active HD-tDCS will be applied at the beginning of 45min speech-language therapy session and will last for 20 min.
Sham HD-tDCS will be applied at the beginning of 45min speech-language therapy session.
Outcomes
Primary Outcome Measures
Change in oral naming (trained items)
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)
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)
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)
We will investigate any changes in performance from pre- to post-treatment levels of change in % accuracy in untrained items.
Secondary Outcome Measures
Change in other language and cognitive task performances (global cognitive changes)
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
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.
Full Information
NCT ID
NCT02606422
First Posted
November 11, 2015
Last Updated
August 31, 2023
Sponsor
Johns Hopkins University
Collaborators
National Institutes of Health (NIH), National Institute on Deafness and Other Communication Disorders (NIDCD)
1. Study Identification
Unique Protocol Identification Number
NCT02606422
Brief Title
tDCS Intervention in Primary Progressive Aphasia
Official Title
Effects of Transcranial Direct Current Stimulation (tDCS) in Spoken and Written Production in Primary Progressive Aphasia (PPA)
Study Type
Interventional
2. Study Status
Record Verification Date
August 2023
Overall Recruitment Status
Recruiting
Study Start Date
April 2013 (undefined)
Primary Completion Date
October 2023 (Anticipated)
Study Completion Date
October 2023 (Anticipated)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Johns Hopkins University
Collaborators
National Institutes of Health (NIH), National Institute on Deafness and Other Communication Disorders (NIDCD)
4. Oversight
Data Monitoring Committee
Yes
5. Study Description
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 high definition transcranial direct current stimulation (HD-tDCS) during language therapy in PPA participants over time. Anodal HD-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 HD-tDCS in individuals with PPA. A better understanding of the therapeutic and neuromodulatory mechanisms of HD-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 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 1-2mA (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 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 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 arelady published a tDCS study on the behavioral results for the improvement of spelling abilities.
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Primary Progressive Aphasia, MCI, FTD
Keywords
transcranial direct current stimulation (tDCS), neurodegeneration, language therapy, Primary Progressive Aphasia (PPA)
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Crossover Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
70 (Anticipated)
8. Arms, Groups, and Interventions
Arm Title
Active HD-tDCS plus Speech-Language Therapy
Arm Type
Experimental
Arm Description
Active HD-tDCS will be applied at the beginning of 45min speech-language therapy session and will last for 20 min.
Arm Title
Sham plus Speech-Language Therapy
Arm Type
Sham Comparator
Arm Description
Sham HD-tDCS will be applied at the beginning of 45min speech-language therapy session.
Intervention Type
Device
Intervention Name(s)
Active HD-tDCS plus Speech-Language Therapy
Intervention Description
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.
Intervention Type
Device
Intervention Name(s)
Sham plus Speech-Language Therapy
Intervention Description
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.
Primary Outcome Measure Information:
Title
Change in oral naming (trained items)
Description
We will investigate any changes in performance from pre- to post-treatment levels of change in % accuracy in trained items.
Time Frame
35 weeks
Title
Change in written naming (trained items)
Description
We will investigate any changes in performance from pre- to post-treatment levels of change in % accuracy in trained items.
Time Frame
35 weeks
Title
Change in oral naming (untrained items)
Description
We will investigate any changes in performance from pre- to post-treatment levels of change in % accuracy in untrained items.
Time Frame
35 weeks
Title
Change in written naming (untrained items)
Description
We will investigate any changes in performance from pre- to post-treatment levels of change in % accuracy in untrained items.
Time Frame
35 weeks
Secondary Outcome Measure Information:
Title
Change in other language and cognitive task performances (global cognitive changes)
Description
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.
Time Frame
35 weeks
Title
Changes in functional connectivity
Description
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.
Time Frame
35 weeks
10. Eligibility
Sex
All
Minimum Age & Unit of Time
50 Years
Maximum Age & Unit of Time
90 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria:
Must be clinically diagnosed with svPPA, nfvPPA or 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.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Kyrana Tsapkini, PhD
Phone
4107362940
Email
tsapkini@jhmi.edu
First Name & Middle Initial & Last Name or Official Title & Degree
Kelly Williamson, M.S.
Email
kwill261@jh.edu
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Kyrana Tsapkini, PhD
Organizational Affiliation
Johns Hopkins University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Johns Hopkins Hospital
City
Baltimore
State/Province
Maryland
ZIP/Postal Code
21204
Country
United States
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Kyrana Tsapkini, PhD
Phone
410-736-2940
Email
tsapkini@jhmi.edu
First Name & Middle Initial & Last Name & Degree
Olivia Herrmann, CCC-SLP
Email
oherrma1@jh.edu
First Name & Middle Initial & Last Name & Degree
Kyrana Tsapkini, PhD
First Name & Middle Initial & Last Name & Degree
Argye Hillis, MD
12. IPD Sharing Statement
Citations:
PubMed Identifier
26062526
Citation
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.
Results Reference
background
PubMed Identifier
26097278
Citation
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.
Results Reference
result
PubMed Identifier
34875098
Citation
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.
Results Reference
derived
PubMed Identifier
33031971
Citation
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.
Results Reference
derived
Links:
URL
http://www.ncbi.nlm.nih.gov/pubmed/26097278
Description
Tsapkini 2014
URL
http://www.ncbi.nlm.nih.gov/pubmed/26062526
Description
Tsapkini 2015
Learn more about this trial
tDCS Intervention in Primary Progressive Aphasia
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