Treating Primary Progressive Aphasia (PPA) Using High-definition tDCS

Phase 2

Active, not recruiting

• Conditions: Primary Progressive Aphasia
• Interventions: Device: high-definition transcranial direct current stimulation; Behavioral: modified constraint-induced language therapy

• Registration Number: NCT04046991
• Lead Sponsor: University of Pennsylvania

Brief Summary

This is a double-blind, sham-controlled, crossover study in which subjects with the non-fluent/agrammatic and logopenic variants of primary progressive aphasia (naPPA and lvPPA, respectively) will undergo language testing and structural and functional brain imaging before and after receiving 10 semi-consecutive daily sessions of real or sham high-definition transcranial direct current stimulation (HD-tDCS) paired with modified constraint-induced language therapy (mCILT). Language testing and brain imaging will be repeated immediately after completion of and 3 months following completion of treatment. The 3-month follow-up will be the primary endpoint. The investigators will examine changes in language performance induced by HD-tDCS + mCILT compared to sham HD-tDCS + mCILT. The investigators will also use network science to analyze brain imaging (fMRI) data to identify network properties associated with baseline PPA severity and tDCS-induced changes in performance. This study will combine knowledge gained from our behavioral, imaging, and network data in order to determine the relative degrees to which these properties predict whether persons with PPA will respond to intervention.

Detailed Description

The central framework for the project is a double-blind, sham-controlled, crossover study in which subjects with the non-fluent/agrammatic and logopenic variants of primary progressive aphasia (naPPA and lvPPA, respectively) will undergo language testing and structural and functional brain imaging before and after receiving 10 semi-consecutive daily sessions of real or sham high definition transcranial direct current stimulation (HD-tDCS) paired with modified constraint-induced language therapy (mCILT). Language testing and brain imaging will be repeated immediately after completion of and 3 months following completion of treatment.

Subjects with naPPA and lvPPA will be randomized to one of two study arms: HD-tDCS+mCILT or sham stimulation+mCILT paired with pre- and post-stimulation imaging and behavioral measures. Equal numbers of subjects with naPPA and lvPPA will be randomized to the HD-tDCS + mCILT and sham + mCILT study arms. The study is double-blinded, in that neither the subject nor the study personnel administering HD-tDCS or sham stimulation will know which arm of the study the subject has been randomized into. Study coordinators will administer HD-tDCS by entering a pre-determined code that has been programmed into the device by another member of the study team. Data will be digitally audio-recorded and analyzed off-line, such that study team members performing data coding and analysis will likewise be blinded to the treatment condition of each subject.

Subject participation in this protocol will occur during 27 planned visits that will span approximately 8 months. The events of the study visits are described below:

VISIT 1:

a Informed consent and screening b. Baseline language assessment #1 c. Baseline MRI scanning

VISIT 2:

Baseline language assessment #2

VISITS 3-11:

HD-tDCS+mCILT OR sham stimulation+mCILT, depending on the study arm to which they had been randomized.

VISIT 12:

1. Final session of HD-tDCS+mCILT or sham stimulation+mCILT

2. Follow-up language assessment

3. Follow-up MRI

VISIT 13:

6-Week follow-up language assessment

VISIT 14:

1. 12-week follow-up language assessment

2. 12-week follow-up MRI

\*\*CROSSOVER\*\*

VISIT 15:

Crossover baseline language assessment #2

VISITS 16-24:

HD-tDCS+mCILT or sham stimulation+mCILT

VISIT 25:

1. 10th session of HD-tDCS+mCILT or sham stimulation+mCILT

2. Follow-up language assessment

3. Follow-up MRI

VISIT 26:

6 Week follow-up language assessment:

VISIT 27:

1. 12-week follow-up language assessment

2. 12-week follow-up MRI

Study Timeline

• Study First Submitted: 2019-07-12
• Study First Submitted QC: 2019-08-05
• Study First Posted: 2019-08-06
• Study Start: 2020-08-17
• Status Verified: 2024-10
• Last Update Submitted: 2024-10-14
• Last Update Posted: 2024-10-15
• Primary Completion: 2025-06-30
• Study Completion: 2025-06-30

Recruitment & Eligibility

• Status: ACTIVE_NOT_RECRUITING
• Sex: All
• Target Recruitment: 66

Inclusion Criteria

1. Presence of aphasia attributable to nonfluent agrammatic PPA (naPPA) or logopenic variant PPA (lvPPA)
2. High school education (or more)
3. Must be able to understand the nature of the study, and give informed consent
4. Native English speaker

Read More

Exclusion Criteria

• Presence of additional neurological illness such as stroke or traumatic brain injury
• Diagnosis of epilepsy or reoccurening seizures
• Pacemaker or ICDs
• Craniotomy or skull breech
• Small vessel disease

Read More

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
HD-tDCS+mCILT	high-definition transcranial direct current stimulation	Participants will undergo 10 daily sessions (Monday-Friday, x2 weeks) of HD-tDCS for 20 minutes using a montage in which a central electrode (1.5mA) is placed over the left frontotemporal area and four surrounding cathodes (.375mA each). Subjects will participate in a modified constraint-induced language therapy.
Sham+mCILT	high-definition transcranial direct current stimulation	Participants will undergo 10 daily sessions (Monday-Friday, x2 weeks) of sham for 20 minutes using a montage in which a central electrode is placed over the left frontotemporal area and four surrounding cathodes. Subjects will participate in a modified constraint-induced language therapy,
HD-tDCS+mCILT	modified constraint-induced language therapy	Participants will undergo 10 daily sessions (Monday-Friday, x2 weeks) of HD-tDCS for 20 minutes using a montage in which a central electrode (1.5mA) is placed over the left frontotemporal area and four surrounding cathodes (.375mA each). Subjects will participate in a modified constraint-induced language therapy.
Sham+mCILT	modified constraint-induced language therapy	Participants will undergo 10 daily sessions (Monday-Friday, x2 weeks) of sham for 20 minutes using a montage in which a central electrode is placed over the left frontotemporal area and four surrounding cathodes. Subjects will participate in a modified constraint-induced language therapy,

Primary Outcome Measures

Name	Time	Method
Change in Western Aphasia Battery Aphasia Quotient (WAB-AQ)	Baseline, 2 weeks, 6 weeks, 12 weeks, 14 weeks, 18 weeks, 24 weeks	The primary outcome measure will be the change in score on the WAB-AQ, a score assessing overall aphasia recovery. Scores can range from 0-100. 0-25 is very severe, 26-50 is severe, 51-75 is moderate, and 76-above is mild. A score of 93 or higher is considered recovered.

Trial Locations

Locations (1)

University of Pennsylvania; 🇺🇸 Philadelphia, Pennsylvania, United States