tDCS Intervention in Primary Progressive Aphasia

NCT02606422 | Completed Results DMC

• 2 other identifiers: NA_00071337R01DC014475
• Study Type: interventional
• Target: 61
• Locations: 1 country
• Sites: 1

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.

Conditions

Primary Progressive Aphasia; MCI; FTD

Keywords

transcranial direct current stimulation (tDCS); neurodegeneration; language therapy; Primary Progressive Aphasia (PPA)

Outcome Measures

Primary Outcomes (4)

• Absolute Percent Change in Written Naming (Trained Items)

  The primary outcome measure was the absolute percentage change in the number of correct letters in the written response, compared to the target response in the trained word lists. This calculation reflects the change in accuracy between two timepoints. For letter accuracy scoring, a rule-based system was used where each letter was assigned one point if correct. Points were deducted for errors such as deletions, additions, substitutions, transpositions, or movements of letters. A second reviewer independently scored the responses and resolved any discrepancies through discussion to ensure consensus. Interrater reliability for letter accuracy scoring was 95%. Average letter accuracy per word was calculated for all trained items. Then the absolute percentage change was calculated by subtracting the earlier time point value (e.g., baseline) from the later one (e.g., immediately after treatment, 2 weeks post, and 2 months post), reflecting the change in accuracy.

  Change from Baseline to Immediately after treatment (3 weeks), 2 weeks post treatment (5 weeks), and 2 months post-treatment (11 weeks) for each period of intervention

• Absolute Percent Change in Written Naming (Untrained Items)

  The primary outcome measure was the absolute percentage change in the number of correct letters in the written response, compared to the target response in the untrained word lists.This calculation reflects the change in accuracy between two timepoints. For letter accuracy scoring, a rule-based system was used where each letter was assigned one point if correct. Points were deducted for errors such as deletions, additions, substitutions, transpositions, or movements of letters. A second reviewer independently scored the responses and resolved any discrepancies through discussion to ensure consensus. Interrater reliability for letter accuracy scoring was 95%. Average letter accuracy per word was calculated for all untrained items. Then the absolute percentage change was calculated by subtracting the earlier time point value (e.g., baseline) from the later one (e.g., immediately after treatment, 2 weeks post, and 2 months post), reflecting the change in accuracy.

  Change from Baseline to Immediately after treatment (3 weeks), 2 weeks post treatment (5 weeks), and 2 months post-treatment (11 weeks) for each period of intervention

• Absolute Percent Change in Oral Naming (Trained Items)

  The percent accuracy for each participant's trained oral naming list was calculated, with scores ranging from 0% to 100%. A score of 0% indicates no correct responses, while 100% represents perfect accuracy. Higher percentages reflect better performance. To assess changes in performance from pre- to post-treatment, the percent accuracy for untrained items was compared before and after the intervention. The absolute percentage change was then calculated by subtracting the accuracy at the baseline time point (e.g., baseline) from the accuracy at the later time points (e.g., immediately after treatment, 2 weeks post, and 2 months post). This reflects the change in the participant's ability to name trained items, expressed as absolute percent change. A positive difference indicates improvement in naming accuracy, with a larger change reflecting greater improvement. A negative difference indicates a decline, with a larger change reflecting greater deterioration in naming ability.

  Change from Baseline to Immediately after treatment (3 weeks), 2 weeks post treatment (5 weeks), and 2 months post-treatment (11 weeks) for each period of intervention

• Absolute Percent Change in Oral Naming (Untrained Items)

  The percent accuracy for each participant's untrained oral naming list was calculated, with scores ranging from 0% to 100%. A score of 0% indicates no correct responses, while 100% represents perfect accuracy. Higher percentages reflect better performance. To assess changes in performance from pre- to post-treatment, the percent accuracy for untrained items was compared before and after the intervention. The absolute percentage change was then calculated by subtracting the accuracy at the baseline time point (e.g., baseline) from the accuracy at the later time points (e.g., immediately after treatment, 2 weeks post, and 2 months post). This reflects the change in the participant's ability to name trained items, expressed as absolute percent change. A positive difference indicates improvement in naming accuracy, with a larger change reflecting greater improvement. A negative difference indicates a decline, with a larger change reflecting greater deterioration in naming ability.

  Change from Baseline to Immediately after treatment (3 weeks), 2 weeks post treatment (5 weeks), and 2 months post-treatment (11 weeks) for each period of intervention

Secondary Outcomes (2)

• Change in Sentence Comprehension as Measured by the Subject Object Active Passive (SOAP) Test

  Change from baseline to immediate follow-up (3 weeks).

• Change in Functional Connectivity

  Change from before treatment to immediate follow up (3 weeks)

Study Arms (2)

Active HD-tDCS plus Speech-Language Therapy

EXPERIMENTAL

Active HD-tDCS will be applied at the beginning of 45min speech-language therapy session and will last for 20 min.

Device: Active HD-tDCS plus Speech-Language Therapy

Sham plus Speech-Language Therapy

SHAM COMPARATOR

Sham HD-tDCS will be applied at the beginning of 45min speech-language therapy session.

Device: Sham plus Speech-Language Therapy

Interventions

Active HD-tDCS plus Speech-Language Therapy DEVICE

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.

Active HD-tDCS plus Speech-Language Therapy

Sham plus Speech-Language Therapy DEVICE

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.

Sham plus Speech-Language Therapy

Eligibility Criteria

• Age: 50 Years - 90 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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).
• Severe claustrophobia.
• Cardiac pacemakers or ferromagnetic implants.
• Pregnant women.

Sponsors & Collaborators

• Johns Hopkins University: lead
• National Institutes of Health (NIH): collaborator
• National Institute on Deafness and Other Communication Disorders (NIDCD): collaborator

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21204, United States

Location

Related Publications (6)

• 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.

  PMID: 26097278 BACKGROUND

• 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.

  PMID: 26062526 BACKGROUND

• Tsapkini K, Webster KT, Ficek BN, Desmond JE, Onyike CU, Rapp B, Frangakis CE, Hillis AE. Electrical brain stimulation in different variants of primary progressive aphasia: A randomized clinical trial. Alzheimers Dement (N Y). 2018 Sep 5;4:461-472. doi: 10.1016/j.trci.2018.08.002. eCollection 2018.

  PMID: 30258975 RESULT

• Wang Z, Ficek BN, Webster KT, Herrmann O, Frangakis CE, Desmond JE, Onyike CU, Caffo B, Hillis AE, Tsapkini K. Specificity in Generalization Effects of Transcranial Direct Current Stimulation Over the Left Inferior Frontal Gyrus in Primary Progressive Aphasia. Neuromodulation. 2023 Jun;26(4):850-860. doi: 10.1016/j.neurom.2022.09.004. Epub 2022 Oct 28.

  PMID: 37287321 DERIVED

• 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.

  PMID: 34875098 DERIVED

• 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.

  PMID: 33031971 DERIVED

Related Links

• Tsapkini 2014
• Tsapkini 2015

MeSH Terms

Conditions

Aphasia, Primary Progressive; Nerve Degeneration

Interventions

Speech Therapy

Condition Hierarchy (Ancestors)

Dementia; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Aphasia; Speech Disorders; Language Disorders; Communication Disorders; Neurobehavioral Manifestations; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Neurocognitive Disorders; Mental Disorders; Pathologic Processes

Intervention Hierarchy (Ancestors)

Rehabilitation of Speech and Language Disorders; Rehabilitation; Aftercare; Continuity of Patient Care; Patient Care; Therapeutics

Results Point of Contact

• Title: Kyrana Tsapkini
• Organization: Johns Hopkins University School of Medicine

tsapkini@jhmi.edu

410-614-2646

Study Officials

• Kyrana Tsapkini, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: Yes

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: November 11, 2015
• First Posted: November 17, 2015
• Study Start: April 1, 2013
• Primary Completion: July 12, 2023
• Study Completion: August 11, 2023
• Last Updated: January 28, 2025
• Results First Posted: January 28, 2025

Record last verified: 2025-01

Locations

US (1)