HDtDCS in Logopenic Variant PPA: Effects on Language and Neural Mechanisms

Not Applicable

Completed

Conditions: Primary Progressive Aphasia

Interventions: Device: HD-tDCS
Device: Sham

Registration Number: NCT03805659

Lead Sponsor: Medical College of Wisconsin

Brief Summary: This study aims to evaluate the effectiveness of a therapy called High-Definition Transcranial Direct Current Stimulation (HD-tDCS) for the treatment of the language deficits experienced by people with a type of Primary Progressive Aphasia. This study uses a combination of brain imaging, language assessment, language training sessions, and HD-tDCS therapy as well as placebo therapy sessions.

Detailed Description: The logopenic variant of Primary Progressive Aphasia (lvPPA) is an untreatable neurodegenerative disorder that is often referred to as the 'language form' of Alzheimer's Disease (AD). Transcranial Direct Current Stimulation (tDCS) has emerged as a safe and potentially effective tool that appears to enhance language production when delivered during language training. This technology provides a critical opportunity to conduct disease intervention.

In this study, the investigators will test the hypothesis that High-Definition tDCS (HD-tDCS) will improve performance on language tasks by increasing functional connectivity and by regulating abnormal neuronal oscillatory patterns. The rationale for this project is that a determination of the therapeutic efficacy and the associated neural mechanisms of HD-tDCS in lvPPA is likely to offer a scientific framework whereby new stimulation parameters, conditions, and target sites can be deciphered.

This study will test the hypothesis that HD-tDCS will improve performance on language tasks by increasing functional connectivity and by regulating abnormal neuronal oscillatory patterns. The language performance and functional connectivity changes will be determined in a randomized, double-blind, sham-controlled crossover manner, in which a stimulation of up to 2mA in the targeted cortical tissue or sham is administered to 20 lvPPA subjects age 45 years and older. The order of treatments is counterbalanced in a within-subject crossover design. In brief, study participants will receive sham during one treatment period and stimulation during the other treatment period.

Recruitment & Eligibility

Status: COMPLETED

Sex: All

Target Recruitment: 6

Inclusion Criteria

Diagnosed with language variant Primary Progressive Aphasia (lvPPA) subtype, defined as either clinical lvPPA or imaging-supported lvPPA in accordance with the most recent diagnostic criteria (Mesulam., 2001; Gorno-Tempini et al., 2011).
Fluent in English.
45 years of age or older.
Structural brain MRI performed within 3 years prior to enrollment.

Exclusion Criteria

Severe cognitive, auditory or visual impairments that would preclude cognitive testing.
Presence of major untreated or unstable psychiatric disease.
A chronic medical condition that is not treated or is unstable.
The presence of cardiac stimulators or pacemakers.
Any metal implants in the skull
Contraindications to MRI
History of seizures
History of dyslexia or other developmental learning disabilities.

Study & Design

Study Type: INTERVENTIONAL

Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
HD-tDCS, then Sham	HD-tDCS	Subjects receive High Dose transcranial Direct Current Stimulation (HD-tDCS) lasting 20 minutes at an electric current intensity of up to 2mA in the left posterior temporo-parietal cortex (TPC). Stimulation sessions are delivered once a day (QD) for a total of 10 sessions over 2 weeks (Monday-Friday). After a washout period of 16 weeks, subjects receive Sham sessions (no electric current) once a day (QD) for a total of 10 sessions over 2 weeks (Monday-Friday).
HD-tDCS, then Sham	Sham	Subjects receive High Dose transcranial Direct Current Stimulation (HD-tDCS) lasting 20 minutes at an electric current intensity of up to 2mA in the left posterior temporo-parietal cortex (TPC). Stimulation sessions are delivered once a day (QD) for a total of 10 sessions over 2 weeks (Monday-Friday). After a washout period of 16 weeks, subjects receive Sham sessions (no electric current) once a day (QD) for a total of 10 sessions over 2 weeks (Monday-Friday).
Sham, then HD-tDCS	Sham	Subjects receive Sham sessions (no electric current) once a day (QD) for a total of 10 sessions over 2 weeks (Monday-Friday). After a washout period of 16 weeks, subjects receive High Dose transcranial Direct Current Stimulation (HD-tDCS) lasting 20 minutes at an electric current intensity of up to 2mA in the left posterior temporo-parietal cortex (TPC). Stimulation sessions are delivered once a day (QD) for a total of 10 sessions over 2 weeks (Monday-Friday).
Sham, then HD-tDCS	HD-tDCS	Subjects receive Sham sessions (no electric current) once a day (QD) for a total of 10 sessions over 2 weeks (Monday-Friday). After a washout period of 16 weeks, subjects receive High Dose transcranial Direct Current Stimulation (HD-tDCS) lasting 20 minutes at an electric current intensity of up to 2mA in the left posterior temporo-parietal cortex (TPC). Stimulation sessions are delivered once a day (QD) for a total of 10 sessions over 2 weeks (Monday-Friday).

Primary Outcome Measures

Name	Time	Method
Determine Changes in Language Performance After Stimulation Sessions	Language performance was assessed before and after 2-week intervention and during washout periods	Language performance as assessed at baseline and post-stimulation procedure

Secondary Outcome Measures

Name	Time	Method
Determine the Resting State Language Network-level Changes in Left TPC Functional Connectivity.	Language network resting state changes were assessed before and after 2-week intervention and during washout periods	Language network resting state changes after stimulation procedure
Determine the Neuronal Frequency Distribution and Connectivity Measures Associated With the Left TPC as Assessed by MEG.	Resting-state neuronal frequencies and synchronizations changes were assessed before and after 2-week intervention and during washout periods	Resting-state neuronal frequencies and synchronizations changes after stimulation procedure