tDCS Intervention in Primary Progressive Aphasia
| Status: | Recruiting |
|---|---|
| Conditions: | Neurology, Neurology |
| Therapuetic Areas: | Neurology |
| Healthy: | No |
| Age Range: | 50 - 90 |
| Updated: | 9/5/2018 |
| Start Date: | April 2013 |
| End Date: | May 2020 |
| Contact: | Kyrana Tsapkini, PhD |
| Email: | tsapkini@jhmi.edu |
| Phone: | 4107362940 |
Effects of Transcranial Direct Current Stimulation (tDCS) in Spoken and Written Production in Primary Progressive Aphasia (PPA)
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.
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.
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. tDCS Methods:
Participants will take part in 10-15 consecutive training sessions (3-5 per week), separated
by 2 months. Anodal 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 tDCS groups and for a maximum of 30 seconds in
the Sham group. For both interventions (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
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 tDCS+language (henceforth abbr.
tDCS treatment) (word production) and sham 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 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 tDCS experimental
conditions. After 1-3 weeks of 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 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 tDCS. To achieve blinding,
all participants will be fitted with the 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 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 (Tsapkini et al., 2014).
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. tDCS Methods:
Participants will take part in 10-15 consecutive training sessions (3-5 per week), separated
by 2 months. Anodal 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 tDCS groups and for a maximum of 30 seconds in
the Sham group. For both interventions (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
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 tDCS+language (henceforth abbr.
tDCS treatment) (word production) and sham 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 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 tDCS experimental
conditions. After 1-3 weeks of 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 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 tDCS. To achieve blinding,
all participants will be fitted with the 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 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 (Tsapkini et al., 2014).
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.
We found this trial at
1
site
1800 Orleans St.
Baltimore, Maryland 21287
Baltimore, Maryland 21287
410-955-5000
Principal Investigator: Kyrana Tsapkini, PhD
Phone: 410-736-2940
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