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Optimization of Electrical Stimulation Approaches in Three Primary Progressive Aphasia Variants

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ClinicalTrials.gov Identifier: NCT03887481
Recruitment Status : Recruiting
First Posted : March 25, 2019
Last Update Posted : November 21, 2019
Sponsor:
Collaborators:
National Institutes of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Information provided by (Responsible Party):
Johns Hopkins University

Brief Summary:

Language deficits are a common feature of neurodegenerative disorders and the primary deficit in primary progressive aphasia (PPA), a syndrome accounting for about 2/3 of fronto-temporal dementia (FTD) variants, and at least one Alzheimer's disease (AD) variant. Language deficits dramatically impair communication and quality of life, for both patients and patients' caregivers. There are no disease-modifying pharmacological agents for PPA; the only available treatment is speech and language therapy.

The investigators conducted the largest to-date randomized, double-blind, sham-controlled, crossover, clinical trial to determine the effects of transcranial direct current stimulation (tDCS) in PPA. The investigators reported that tDCS over the left inferior frontal gyrus (IFG), one of the major language hubs in the brain, significantly augments the effects of a written naming and spelling intervention.

A key result in the investigators' previous studies, was the discovery of the effects of patient heterogeneity on tDCS effectiveness: patients with different PPA variants, (i.e., with different atrophy patterns, and therefore different language and cognitive deficits), responded differently to tDCS over the left IFG.

Aim 1 of the proposed studies will focus on heterogeneity, using the neuromodulatory principle of 'functional coupling' to determine whether optimizing previous treatment approaches, (i.e., coupling the area of stimulation with the language function the investigators intend to treat in each variant), will improve language functions more than sham. Aim 2 is to understand the mechanisms by which tDCS reduces language deficits PPA. In particular, the investigators will measure tDCS-induced changes in functional connectivity, and in concentrations of the neurotransmitter gamma-aminobutyric acid (GABA), for each stimulation/intervention condition. Aim 3 is to identify the neural, cognitive, clinical and physiological biomarkers that predict treatment effects, both for tDCS and sham. The approach will deal with specific issues of clinical trials, (such as missingness of data), and employ novel analytical methods such as graph-theory analysis and machine learning approaches. Overall, this project will: (i) advance and optimize a promising intervention (tDCS) for a debilitating condition associated with neurodegenerative diseases, (ii) elucidate neural mechanisms for these interventions, and (iii) identify predictors of tDCS neuromodulatory therapies in PPA.


Condition or disease Intervention/treatment Phase
Primary Progressive Aphasia Device: High-definition active tDCS (HD-tDCS) + Language/Cognitive Intervention(s) Device: Sham + Language/Cognitive Intervention(s) Not Applicable

Detailed Description:
This proposal will extend the investigators' previous award, that provided the first evidence from a clinical trial (double-blind, sham-controlled, crossover), on the beneficial effects of transcranial direct current stimulation (tDCS) over the left inferior frontal gyrus in primary progressive aphasia (PPA), a debilitating neurodegenerative disorder affecting primarily language functions. The investigators' previous studies, although it established the augmentative effects of tDCS in PPA and shed light into its possible mechanisms, the investigators also revealed a fundamental gap in the investigators' knowledge, namely the effect of patient heterogeneity on tDCS effects; there are differential effects of PPA variant and baseline functional and structural connectivity on the effectiveness of tDCS. In this present Phase 1/Phase 2 study, the investigators will directly address this knowledge gap by proposing different tDCS targets and interventions for each of the three PPA variants according to deficit (non-fluent variant PPA (nfvPPA), logopenic variant PPA (lvPPA), semantic variant PPA (svPPA)), to optimize the tDCS effects in PPA, uncover the mechanisms, and estimate tDCS predictors.

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 60 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Intervention Model Description: This is a crossover design of active HD-tDCS + Language/Cognitive Intervention(s) that crossovers to Sham + Language/Cognitive Intervention(s) in Arm 1 and Sham + Language/Cognitive Intervention(s) that crossovers to active HD-tDCS + Language/Cognitive Intervention(s) in Arm 2.
Masking: Triple (Participant, Care Provider, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Optimization of Electrical Stimulation Approaches in Three Primary Progressive Aphasia Variants
Actual Study Start Date : August 28, 2019
Estimated Primary Completion Date : January 2026
Estimated Study Completion Date : January 2026


Arm Intervention/treatment
Experimental: Active HD-tDCS + Language/Cognitive Intervention(s) first
Participants will receive active HD-tDCS + Language/Cognitive Intervention(s) first and then receive Sham + Language/Cognitive Intervention(s) after a three-month washout period.
Device: High-definition active tDCS (HD-tDCS) + Language/Cognitive Intervention(s)

Device: Active HD-tDCS 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 (Supramarginal Gyrus, Middle Frontal Gyrus or Middle Temporal Gyrus depending on the variant of Primary Progressive Aphasia). The stimulation will be delivered at an intensity of 2 milliamperes (mA) in a ramp-like fashion for a maximum of 20 minutes.

Behavioral: Language/Cognitive Intervention(s) For nfvPPA, participants will complete the n-back task (1-back and 2-back) for visual letters and auditory words. For lvPPA, participants will be asked to recall a total of two different lists, consisting of 10 semantically and phonologically unrelated word sequences each. For svPPA, one list of 12 semantically related written words with corresponding pictorial representations will be presented incrementally (pairs, triplets, etc.) and participants will be instructed to match words with pictures.


Device: Sham + Language/Cognitive Intervention(s)

Device: Sham Current will be administered in a ramp-like fashion but after the ramping phase the intensity will drop to 0 mA. Current under the Sham condition will last for a maximum of 30 seconds.

Behavioral: Language/Cognitive Intervention(s) For nfvPPA, participants will complete the n-back task (1-back and 2-back) for visual letters and auditory words. For lvPPA, participants will be asked to recall a total of two different lists, consisting of 10 semantically and phonologically unrelated word sequences each. For svPPA, one list of 12 semantically related written words with corresponding pictorial representations will be presented incrementally (pairs, triplets, etc.) and participants will be instructed to match words with pictures.


Experimental: Sham + Language/Cognitive Intervention(s) first
Participants will receive Sham + Language/Cognitive Intervention(s) first and then receive active HD-tDCS + Language/Cognitive Intervention(s) after a three-month washout period.
Device: High-definition active tDCS (HD-tDCS) + Language/Cognitive Intervention(s)

Device: Active HD-tDCS 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 (Supramarginal Gyrus, Middle Frontal Gyrus or Middle Temporal Gyrus depending on the variant of Primary Progressive Aphasia). The stimulation will be delivered at an intensity of 2 milliamperes (mA) in a ramp-like fashion for a maximum of 20 minutes.

Behavioral: Language/Cognitive Intervention(s) For nfvPPA, participants will complete the n-back task (1-back and 2-back) for visual letters and auditory words. For lvPPA, participants will be asked to recall a total of two different lists, consisting of 10 semantically and phonologically unrelated word sequences each. For svPPA, one list of 12 semantically related written words with corresponding pictorial representations will be presented incrementally (pairs, triplets, etc.) and participants will be instructed to match words with pictures.


Device: Sham + Language/Cognitive Intervention(s)

Device: Sham Current will be administered in a ramp-like fashion but after the ramping phase the intensity will drop to 0 mA. Current under the Sham condition will last for a maximum of 30 seconds.

Behavioral: Language/Cognitive Intervention(s) For nfvPPA, participants will complete the n-back task (1-back and 2-back) for visual letters and auditory words. For lvPPA, participants will be asked to recall a total of two different lists, consisting of 10 semantically and phonologically unrelated word sequences each. For svPPA, one list of 12 semantically related written words with corresponding pictorial representations will be presented incrementally (pairs, triplets, etc.) and participants will be instructed to match words with pictures.





Primary Outcome Measures :
  1. Change in N-back letter task score (1-back) (for non-fluent variant PPA) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    The N-back task is a well-established task that assesses working memory and working memory capacity. Participants are presented with letters in sequence and are instructed to reply whether the current letter matches the one presented immediately before. Scoring will be based on the total number of correct responses (hit rate) minus the number of incorrect responses (false alarm rate). The investigators will compute the change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  2. Change in N-back letter task score (2-back) (for non-fluent variant PPA) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    The N-back task is a well-established task that assesses working memory and working memory capacity. Participants are presented with letters in sequence and are instructed to reply whether the current letter matches the one presented 2 letters ago. Scoring will be based on the total number of correct responses (hit rate) minus the number of incorrect responses (false alarm rate). The investigators will compute the change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  3. Change in N-back word task score (1-back) (for non-fluent variant PPA) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    The N-back task is a well-established task that assesses working memory and working memory capacity. Participants are presented with words in sequence and are instructed to reply whether the current word matches the one presented immediately before. Scoring will be based on the total number of correct responses (hit rate) minus the number of incorrect responses (false alarm rate). The investigators will compute the change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  4. Change in N-back word task score (2-back) (for non-fluent variant PPA) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    The N-back task is a well-established task that assesses working memory and working memory capacity. Participants are presented with words in sequence and are instructed to reply whether the current word matches the one presented 2 words ago. Scoring will be based on the total number of correct responses (hit rate) minus the number of incorrect responses (false alarm rate). The investigators will compute the change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  5. Change in syntactic comprehension as assessed by Subject-relative, Object-relative, Active, Passive (S.O.A.P.) Syntactic Battery (for non-fluent variant PPA) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    The 40-item Subject-relative, Object-relative, Active, Passive (S.O.A.P.) Syntactic Battery of various sub-tests will be used to assess argument structure comprehension and production. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  6. Change in maximum list length forward score of semantically unrelated trained word sequences (for logopenic variant PPA) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Each trained list (practiced during the intervention period) will consist of 10 semantically unrelated word sequences which will target verbal short-term memory/working memory. Immediately following verbal presentation of each word sequence in each list, participants will be instructed to recall it in the forward serial order. Successful pass of each list is considered a score above 50% of sequences correctly recalled. Following successful pass of the first list, participants will be presented with a second list of 10 word sequences in which every sequence has an additional word as compared to the previous list. Scoring will be based on the Temple Assessment of Language and Short-Term Memory in Aphasia test #14 method, which takes into account the maximum list length number in which the participants scored above 50%. The investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in scores is considered a benefit.

  7. Change in maximum list length backward score of semantically unrelated trained word sequences (for logopenic variant PPA) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Each trained list (practiced during the intervention period) will consist of 10 semantically unrelated word sequences which will target verbal short-term memory/working memory. Immediately following verbal presentation of each word sequence in each list, participants will be instructed to recall it in the backward serial order. Successful pass of each list is considered a score above 50% of sequences correctly recalled. Following successful pass of the first list, participants will be presented with a second list of 10 word sequences in which every sequence has an additional word as compared to the previous list. Scoring will be based on the Temple Assessment of Language and Short-Term Memory in Aphasia test #14 method, which takes into account the maximum list length number in which the participants scored above 50%. The investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in scores is considered a benefit.

  8. Change in word accuracy of semantically unrelated trained word sequences forward (for logopenic variant PPA) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Each trained list (practiced during the intervention period) will consist of 10 semantically unrelated word sequences which will target verbal short-term memory/working memory. Immediately following verbal presentation of each word sequence in each list, participants will be instructed to recall it on the forward serial order. Successful pass of each list is considered a score above 50% of sequences correctly recalled. Following successful pass of the first list, participants will be presented with a second list of 10 word sequences in which every sequence has an additional word as compared to the previous list. The investigators will compute the number of words correctly recalled whether in the right order within a sequence or not, and transform the score to percent correct (range: 0-100). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in scores is considered a benefit.

  9. Change in word accuracy of semantically unrelated trained word sequences backward (for logopenic variant PPA) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Each trained list (practiced during the intervention period) will consist of 10 semantically unrelated word sequences which will target verbal short-term memory/working memory. Immediately following verbal presentation of each word sequence in each list, participants will be instructed to recall it on the backward serial order. Successful pass of each list is considered a score above 50% of sequences correctly recalled. Following successful pass of the first list, participants will be presented with a second list of 10 word sequences in which every sequence has an additional word as compared to the previous list. The investigators will compute the number of words correctly recalled whether in the right order within a sequence or not, and transform the score to percent correct (range: 0-100). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in scores is considered a benefit.

  10. Change in maximum list length forward score of semantically unrelated untrained TALSA word spans (for logopenic variant PPA) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Temple Assessment of Language and Short-Term Memory (TALSA) tasks include repetition of semantically unrelated word spans, with lists consisting of spans between 1 and 6 words. Participants will be instructed to recall the word spans in forward serial order Scoring takes into account the maximum list length number in which the participants scored above 50% (5/10 sequences correctly recalled). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in scores is considered a benefit.

  11. Change in maximum list length backward score of semantically unrelated untrained TALSA word spans (for logopenic variant PPA) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Temple Assessment of Language and Short-Term Memory (TALSA) tasks include repetition of semantically unrelated word spans, with lists consisting of spans between 1 and 6 words. Participants will be instructed to recall the word spans in backwards serial order. Scoring takes into account the maximum list length number in which the participants scored above 50% (5/10 sequences correctly recalled). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in scores is considered a benefit.

  12. Change in word accuracy of semantically unrelated untrained TALSA word spans forward (for logopenic variant PPA) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Temple Assessment of Language and Short-Term Memory (TALSA) tasks include repetition of semantically unrelated word spans, with lists consisting of spans between 1 and 6 words. Participants will be instructed to recall the word spans in forward serial order. The investigators will compute the number of words correctly recalled whether in the right order within a span or not, and transform the score to percent correct (range: 0-100). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in scores is considered a benefit.

  13. Change in word accuracy of semantically unrelated untrained TALSA word spans backward (for logopenic variant PPA) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Temple Assessment of Language and Short-Term Memory (TALSA) tasks include repetition of semantically unrelated word spans, with lists consisting of spans between 1 and 6 words. Participants will be instructed to recall the word spans in backward serial order. The investigators will compute the number of words correctly recalled whether in the right order within a span or not, and transform the score to percent correct (range: 0-100). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in scores is considered a benefit.

  14. Change in word/picture association accuracy of semantically related trained words/pictures (for semantic variant PPA) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Each trained list (practiced during the intervention period) will consist of 12 semantically related written words and pictures. This task is modeled on the written-word picture matching subtest of the Psycholinguistic Assessments of Language Processing in Aphasia (PALPA) which assesses semantic comprehension ability. Participants will be asked to match all 12 written words to participants' pictorial representations at once. The investigators will compute the raw score of words/pictures correctly matched and transform to percent correct (range 0-100). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  15. Change in Mnemonic Similarity Task (MST) score (for semantic variant PPA) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    MST is a well-established test in order to assess high interference memory and general recognition memory via pattern separation. It involves differentiating between previously learned images and novel images. For the MST tasks, the Pattern Separation (PS) score will be calculated using two measures: a) the difference between the rate of "Similar" responses given to the lure items minus "Similar" responses given to the foils (lure discrimination index, LDI); b) the difference between the rate of "Old" responses given to repeat items minus "Old" responses given to foils (recognition, REC). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in scores is considered a benefit.


Secondary Outcome Measures :
  1. Change in PALPA written word-picture matching score [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    This task uses written word-picture matching in order to assess semantic comprehension ability. Participants will be asked to match one written word to its pictorial representation while 4 other pictures will be present as distractors. The investigators will compute the raw score of words/pictures correctly matched and transform to percent correct (range 0-100). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  2. Change in Mnemonic Similarity Task (MST) score [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    MST is a well-established test in order to assess high interference memory and general recognition memory via pattern separation. It involves differentiating between previously learned images and novel images. For the MST tasks, the Pattern Separation (PS) score will be calculated using two measures: a) the difference between the rate of "Similar" responses given to the lure items minus "Similar" responses given to the foils (lure discrimination index, LDI); b) the difference between the rate of "Old" responses given to repeat items minus "Old" responses given to foils (recognition, REC). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in scores is considered a benefit.

  3. Change in TALSA word repetition score [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    TALSA tasks include word repetition. Scoring will be based on percent of words correctly repeated. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  4. Change in TALSA non-word repetition score [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    TALSA tasks include non-word repetition. Scoring will be based on percent of non-words correctly repeated. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  5. Change in TALSA word repetition span score [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    TALSA tasks include word repetition span, with sets of 1-6 words. Scoring will be based on percent of words correctly repeated. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  6. Change in TALSA non-word repetition span score [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    TALSA tasks include non-word repetition span, with sets of 1-6 non-words. Scoring will be based on percent of non-words correctly repeated. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  7. Change in TALSA sentence repetition score [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Sentence repetition tasks come from the TALSA, with scoring based on percent of words in sentences correctly repeated. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  8. Change in TALSA semantic, phonological, unrelated word repetition span score [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    TALSA tasks include word repetition span with systemic variations of the relatedness of the words. The span includes words which are semantically or phonologically related as well as unrelated words which are part of the same word sequence. Scoring will be based on the total number of spans correctly recalled. The investigators will compute the change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  9. Change in monitoring/manipulation task score [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Investigators will use a modified version the Champod and Petrides task using fewer learned words in a list. This task assesses verbal learning of word sequences with monitoring and manipulation demands. Scoring will be based on the total number of correct responses. The investigators will compute the change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  10. Change in N-back task score [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    The N-back task is a well-established task that assesses working memory and working memory capacity. Participants are presented with abstract and concrete words in sequentially and are instructed to reply whether the current word matches the one presented n-steps (1 and 2 -steps in the present study) back. Scoring will be based on the total number of correct responses (hit rate) minus the number of incorrect responses (false alarm rate). The investigators will compute the change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  11. Change in attention and manipulation of information score (seconds) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Using the Trail Making Test (TMT) parts A and B, which include the sequential connection of letters/numbers in order to complete a trail, the investigators will obtain the time (seconds) required by the participants to finish the tasks. Decrease in the time is considered a benefit.

  12. Change in the Attention Network Task (ANT) score [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    The Attention Network Task involves the presentation of two empty boxes which are filled with a sequence of arrows in a timely manner. The participant is instructed to indicate as fast as he/she can the direction of the middle arrow. Scoring will be based on the total number of correct responses as well as the reaction time. The investigators will compute the change in outcome in percent difference between before intervention and each time point after. Increase in accuracy and decrease in reaction time is considered a benefit.

  13. Change in Rey Auditory-Verbal Learning Test (RAVLT) score [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    RAVLT is a well-established verbal memory test. RAVLT includes a 5-trial presentation of a 15-word list (List A), a single presentation of an interference list (List B)(Trial 6), two post-interference recall trials (one immediate - Trial 7, one delayed - Trial 8) and recognition of the target words in the orthographic modality with distractors (Trial 9). Scoring includes the percent score of Trial 1, Trial 5, Trial 8 and Trial 9 as well as the sum of Trial 1 through 5, and the difference between Trial 5 and Trial 1. The investigators will compute the percent difference between the scores before intervention and each time point after. Increase in score is considered a benefit.

  14. Change in semantic content of connected speech [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Using the Cookie Theft image from the Boston Diagnostic Aphasia Examination (BDAE) and the Circus image from the Apraxia Battery for Adults (ABA) investigators will obtain representative language samples as participants describe the images. The investigators will compute the raw score of items (semantics) correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  15. Change in oral naming Boston Naming Test score [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    The Boston Naming Test is a widely used picture naming test that detects lexical retrieval deficits in the oral modality. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  16. Change in oral naming Philadelphia Naming Test score [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    The Philadelphia Naming Test is an extensive picture naming test that comprises 275 items from a wide range of frequencies and other psycholinguistic characteristics. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  17. Change in written naming as assessed by Boston Naming Test [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Accuracy in written picture naming of the 30-item Boston Naming Test will be assessed. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  18. Change in written naming as assessed by Philadelphia Naming Test [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Accuracy in written picture naming using the Philadelphia Naming Test will be assessed. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  19. Change in oral naming of action as assessed by Hopkins Assessment of Naming Actions (HANA) [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Accuracy in oral naming of actions will be assessed using HANA. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100%), computing change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  20. Change in spelling as assessed by the Johns Hopkins Dysgraphia battery [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Accuracy in spelling using the Johns Hopkins Dysgraphia battery will be assessed. The investigators will compute the raw score of items correct using a spelling scoring system accounting for additions, substitutions, and deletions, and transform to percent correct (range: 0-100%), computing change in outcome in percent difference before intervention and each time point after. Increase in score is considered a benefit.

  21. Change in syntactic comprehension as assessed by Subject-relative, Object-relative, Active, Passive (S.O.A.P.) Syntactic Battery [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    The 40-item Subject-relative, Object-relative, Active, Passive (S.O.A.P.) Syntactic Battery of various sub-tests will be used to assess argument structure comprehension and production. The investigators will compute the raw score of items correct and transform to percent correct (range: 0-100). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  22. Change in Northwestern Assessment of Verbs and Sentences (NAVS) Argument Structure Production Test (ASPT) score [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    The Argument Structure Production Test (ASPT) portion of the Northwestern Assessment of Verbs and Sentences (NAVS) will be used to assess verb and verb argument production. The investigators will compute the raw score of sentences with correct word selection and transform to percent correct (range: 0-100). Subsequently, the investigators will compute change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  23. Change in verbal fluency task score [ Time Frame: Before intervention, immediately after intervention, 1 month post intervention, 3 months post intervention ]
    Verbal fluency tasks (semantic and letter fluency) involve generating as many words as possible in one minute. Scoring will be based on number of words generated per minute. The investigators will compute the raw score of items correct and subsequently the percent difference between before intervention and each time point after. Increase in score is considered a benefit.

  24. Change in volumetric measurements of select brain regions [ Time Frame: Before intervention, immediately after intervention and 3 months post each intervention period ]
    Using Magnetization-Prepared Rapid Gradient-Echo (MPRAGE) Magnetic Resonance Imaging (MRI) investigators will perform volumetric measurements of select brain regions. Measurements will be collected in millimeters cubed (mm^3).

  25. Change in functional connectivity of select brain regions (z-correlations) [ Time Frame: Before intervention, immediately after intervention and 3 months post each intervention period ]
    Using resting stage functional MRI (rs-fMRI) investigators will detect activity of various brain regions under a resting/task-negative condition, which will help evaluate functional regional interactions as indicated by the z-correlations between the selected brain area.

  26. Change in Gamma-Aminobutyric Acid (GABA) concentration [ Time Frame: Before intervention, immediately after intervention and 3 months post each intervention period ]
    Using Magnetic Resonance Spectroscopy (MRS) investigators will measure metabolite (GABA) concentrations from select brain regions in international units (IU).

  27. Change in location of white matter tracts of select brain regions [ Time Frame: Before intervention, immediately after intervention and 3 months post each intervention period ]
    Using Diffusion Weighted/Diffusion Tensor Imaging (DWI/DTI) investigators will estimate the location of the brain's white matter tracts on the regions of concern.

  28. Change in anisotropy of white matter tracts of select brain regions [ Time Frame: Before intervention, immediately after intervention and 3 months post each intervention period ]
    Using Diffusion Weighted/Diffusion Tensor Imaging (DWI/DTI) investigators will estimate the anisotropy of the brain's white matter tracts on the brain regions of concern.

  29. Change in sleep efficiency as assessed by actigraphy [ Time Frame: One week before to one week after each period of intervention, up to 8 weeks ]
    Actigraphy for sleep is a method for observing sleep activity patterns. Actigraphy data is gathered via a wrist band with an accelerometer and a light detector. The investigators will compute the sleep efficiency (percentage of time in bed spent asleep) and compute the change in outcome in percent difference between before intervention and each time point after. Increase in score is considered a benefit.



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


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Ages Eligible for Study:   50 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • Must be between 50-80 years of age.
  • Must be right-handed.
  • Must be proficient in English.
  • Must have a minimum of high-school education.
  • Must be diagnosed with Primary Progressive Aphasia (PPA) or with any of the specific PPA variants (non-fluent variant PPA, logopenic variant PPA or semantic variant PPA).
  • Participants will be diagnosed with PPA or with any of the PPA variants in specialized or early dementias clinics at Johns Hopkins University or other specialized centers in the US based on the current consensus criteria.
  • Healthy age- and education-matched controls: The investigators will include 30 healthy age- and education-matched controls, usually spouses, to maximize similarity in terms of other demographic or life-style factors that contribute to language and cognitive performance.

Exclusion Criteria:

  • People with previous neurological disease including vascular dementia (e.g., stroke, developmental dyslexia, dysgraphia or attentional deficit).
  • People with uncorrected hearing loss
  • People with uncorrected visual acuity loss.
  • People with advanced dementia or severe language impairments: Mini Mental State -Examination (MMSE)<18, or Montreal Cognitive Assessment (MOCA)<15, or language Frontotemporal Dementia specific - Clinical Dementia Rating (FTD-CDR)<=2.
  • Left handed individuals.
  • People with pre-existing psychiatric disorders such as behavioral disturbances, severe depression, or schizophrenia that do not allow these people to comply or follow the study schedule and requirements such as repeated evaluation and therapy.

Exclusion Criteria for MRI Participation:

  • People with severe claustrophobia.
  • People with cardiac pacemakers or ferromagnetic implants.
  • Pregnant women.

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03887481


Contacts
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Contact: Kyrana Tsapkini, PhD 410-736-2940 tsapkini@jhmi.edu

Locations
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United States, Maryland
Johns Hopkins Hospital Recruiting
Baltimore, Maryland, United States, 21287
Contact: Kyrana Tsapkini, PhD    410-736-2940    tsapkini@jhmi.edu   
Principal Investigator: Kyrana Tsapkini, PhD         
Sponsors and Collaborators
Johns Hopkins University
National Institutes of Health (NIH)
National Institute on Deafness and Other Communication Disorders (NIDCD)
Investigators
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Principal Investigator: Kyrana Tsapkini, PhD Johns Hopkins University

Publications of Results:

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Responsible Party: Johns Hopkins University
ClinicalTrials.gov Identifier: NCT03887481    
Other Study ID Numbers: IRB00201027
R01DC014475 ( U.S. NIH Grant/Contract )
First Posted: March 25, 2019    Key Record Dates
Last Update Posted: November 21, 2019
Last Verified: November 2019

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: Yes
Product Manufactured in and Exported from the U.S.: No
Keywords provided by Johns Hopkins University:
transcranial direct current stimulation (tDCS)
neurodegeneration
verbal short-term memory
working memory
semantic short-term memory
non-fluent variant
logopenic variant
semantic variant
primary progressive aphasia
Additional relevant MeSH terms:
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Aphasia
Aphasia, Primary Progressive
Pick Disease of the Brain
Frontotemporal Dementia
Speech Disorders
Language Disorders
Communication Disorders
Neurobehavioral Manifestations
Neurologic Manifestations
Nervous System Diseases
Signs and Symptoms
Dementia
Brain Diseases
Central Nervous System Diseases
Neurocognitive Disorders
Mental Disorders
Frontotemporal Lobar Degeneration
TDP-43 Proteinopathies
Neurodegenerative Diseases
Proteostasis Deficiencies
Metabolic Diseases