Effects of tDCS on Apraxia of Speech in Non-Fluent Primary Progressive Aphasia

NCT04486586 | Withdrawn FDA Device

• 1 other identifier: NA_00071337-2
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 1

Brief Summary

Primary progressive aphasia (PPA) is a neurodegenerative disease that affects first and foremost language abilities. There are three different variants of PPA, each a relatively distinct speech and language profile. For individuals with non-fluent variant PPA (nfvPPA), a core symptom is apraxia of speech (AOS), which is defined as an oral motor speech disorder. Such a disorder inhibits one's ability to translate speech plans into motor plans and results in longer segmental durations and reduced rate of syllabic production. This research project investigates the behavioral and neuromodulatory effects of transcranial direct current stimulation (tDCS) during language therapy in participants with nfvPPA 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 (sham). The investigators believe tDCS during language therapy will 1) improve language performance or decrease rate of decline, 2) promote 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 nfvPPA may have a significant impact on the development of effective therapies for PPA, and may offer insight into ways of impeding neurodegeneration that may improve patients' quality of life, as well as extend patients' ability to work and manage patients' affairs.

Conditions

Primary Progressive Aphasia

Keywords

transcranial direct current stimulation (tDCS); neurodegeneration; language therapy; primary progressive aphasia (PPA); apraxia of speech (AOS)

Outcome Measures

Primary Outcomes (6)

• Change in segmental duration of vowels of trained words

  Duration of vowels for trained words (practiced in therapy) will be measured in milliseconds (ms) via acoustic analyses. Investigators will compute the change in outcome over time: before intervention versus each time point after. Decrease in duration is considered a benefit.

  Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention

• Change in segmental duration of vowels of untrained words

  Duration of vowels for untrained words (not practiced in therapy) will be measured in milliseconds (ms) via acoustic analyses. Investigators will compute the change in outcome over time: before intervention versus each time point after. Decrease in duration is considered a benefit.

  Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention

• Change in segmental duration of consonants of trained words

  Duration of consonants for trained words (practiced in therapy) will be measured in milliseconds (ms) via acoustic analyses. Investigators will compute the change in outcome over time: before intervention versus each time point after. Decrease in duration is considered a benefit.

  Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention

• Change in segmental duration of consonants of untrained words

  Duration of consonants for untrained words (not practiced in therapy) will be measured in milliseconds (ms) via acoustic analyses. Investigators will compute the change in outcome over time: before intervention versus each time point after. Decrease in duration is considered a benefit.

  Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention

• Change in speech fluency on trained words

  Speech fluency will be measured on trained words (practiced in therapy) using the mean log of sound duration collected via acoustic analyses. Investigators will compute the change in outcome over time: before intervention versus each time point after. Lower log duration indicates faster speech production. A decrease in sound duration is considered a benefit.

  Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention

• Change in speech fluency on untrained words

  Speech fluency will be measured on untrained words (not practiced in therapy) using the mean log of sound duration collected via acoustic analyses. Investigators will compute the change in outcome over time: before intervention versus each time point after. Lower log duration indicates faster speech production. A decrease in sound duration is considered a benefit.

  Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention

Secondary Outcomes (12)

• Change in prosody/intonation of trained words

  Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention

• Change in prosody/intonation of untrained words

  Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention

• Change in syntactic comprehension as assessed by Subject-relative, Object-relative, Active, Passive (S.O.A.P.) Syntactic Battery

  Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention

• Change in verbal fluency task score

  Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention

• Change in semantic content of connected speech

  Before intervention, immediately after intervention, 2 weeks post intervention and 2 months post intervention

Study Arms (2)

Active tDCS plus Speech-Language Therapy first

EXPERIMENTAL

Active tDCS will be applied at the beginning of 45 minutes speech-language therapy session and then participant will be switched to sham tDCS after a washout period.

Device: Active tDCS plus Speech-Language Therapy; Device: Sham plus Speech-Language Therapy

Sham plus Speech-Language Therapy first

SHAM COMPARATOR

Sham will be applied at the beginning of 45 minutes speech-language therapy session and then participant will be switched to an active tDCS after a washout period.

Device: Active tDCS plus Speech-Language Therapy; Device: Sham plus Speech-Language Therapy

Interventions

Active 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 2 mA (estimated current density 0.04 mA/cm\^2; estimated total charge 0.048 C/cm\^2) in a ramp-like fashion for a maximum of 20 minutes. Speech-language therapy will target apraxia of speech (AOS).

Active tDCS plus Speech-Language Therapy first; Sham plus Speech-Language Therapy first

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 target apraxia of speech (AOS).

Active tDCS plus Speech-Language Therapy first; Sham plus Speech-Language Therapy first

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 nfvPPA or unclassifiable PPA. 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 speaker 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

Study Sites (1)

Johns Hopkins Hospital

Baltimore, Maryland, 21287, United States

Location

MeSH Terms

Conditions

Aphasia, Primary Progressive; Nerve Degeneration; Apraxias

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; Psychomotor Disorders

Intervention Hierarchy (Ancestors)

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

Study Officials

• Kyrana Tsapkini, PhD

  Johns Hopkins University

  PRINCIPAL INVESTIGATOR

Study Design

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

Study Record Dates

• First Submitted: July 20, 2020
• First Posted: July 24, 2020
• Study Start: April 1, 2013
• Primary Completion: April 1, 2025
• Study Completion: April 1, 2025
• Last Updated: April 24, 2025

Record last verified: 2025-04

Locations

US (1)