Primary Progressive AphasiaNCT04566731
Treating Primary Progressive Aphasia (PPA) Using tDCS
A study testing Transcranial Direct Current Stimulation (tDCS) and Modified Contraint-Induced Language Therapy (mCILT) in people with Primary Progressive Aphasia, run by University of Pennsylvania at 1 site in United States.
Trial summary
This is a double-blind, sham-controlled, crossover study in which subjects with the non-fluent/agrammatic and semantic variants of primary progressive aphasia (naPPA and svPPA, respectively) will undergo language testing and structural and functional brain imaging before and after receiving 10 semi-consecutive daily… Read more about this study
- Who is it for?
- Ages 45 to 80 years
- Conditions the study is for
- Primary Progressive Aphasia
- What is being tested?
- Transcranial Direct Current Stimulation (tDCS) and Modified Contraint-Induced Language Therapy (mCILT)
- Type of treatment
- Medical device, Lifestyle or therapy programme
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 23 participants
- Where
- 1 siteUnited States
- Study dates
- 1 Dec 2020to 1 Jul 2024
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 45 to 80 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Presence of aphasia attributable to the semantic variant (svPPA) or non- fluent/agrammatic variant (naPPA) of Primary Progressive Aphasia.
- Must be a native English speaker
Who cannot join
- History of seizures or unexplained loss of consciousness
- Subjects with metallic objects in the face or head other than dental apparatus such as braces, fillings, and implants.
- Subjects with Pacemakers or ICDs.
- Subjects with previous craniotomy or any breach in the skull
- Subjects with a history of other neurological disorder (stroke, TBI, Parkinson)
- Subjects with a history of small vessel disease
Trial locations and contacts
1 site in 1 country.
United States1 site
University of Pennsylvania
Philadelphia, Pennsylvania, 19104
About this study
Official title: Using Transcranial Direct Current Stimulation to Reveal Mechanisms of Language Loss and to Treat Progressive Aphasia Associated With FTD and Related Dementias
This is a double-blind, sham-controlled, crossover study in which subjects with the non-fluent/agrammatic and semantic variants of primary progressive aphasia (naPPA and svPPA, respectively) will undergo language testing and structural and functional brain imaging before and after receiving 10 semi-consecutive daily sessions of real or sham transcranial direct current stimulation (tDCS) paired with modified constraint-induced language therapy (mCILT). Language testing and brain imaging will be repeated immediately after completion of and up-to 24 weeks following completion of treatment. The investigators will examine changes in language performance induced by tDCS + mCILT compared to sham 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.
Read the 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 semantic variants of primary progressive aphasia (naPPA and svPPA, respectively) will undergo language testing and structural and functional brain imaging before and after receiving 10 semi-consecutive daily sessions of real or sham transcranial direct current stimulation (tDCS) paired with modified constraint-induced language therapy (mCILT). Language testing and brain imaging will be repeated immediately after completion of and up-to 24 weeks following completion of treatment.
Subjects with naPPA and svPPA will be randomized to one of two study arms: tDCS+mCILT or sham stimulation+mCILT paired with pre- and post-stimulation imaging and behavioral measures. Equal numbers of subjects with naPPA and svPPA will be randomized to the tDCS + mCILT and sham + mCILT study arms. The study is double-blinded, in that neither the subject nor the study personnel administering tDCS or sham stimulation will know which arm of the study the subject has been randomized into. Study coordinators will administer 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 36 planned visits that will span approximately 12 months. The events of the study visits are described below:
VISIT 1:
Informed consent and screening
VISIT 2:
Baseline MRI
VISIT 3 \& 4:
Baseline language assessment
VISITS 5-14:
tDCS+mCILT OR sham stimulation+mCILT, depending on the study arm to which they had been randomized.
VISIT 15 \& 16:
Follow-up language assessment Follow-up MRI
VISIT 17:
6-Week follow-up language assessment
VISIT 18 \& 19:
12-week follow-up language assessment 12-week follow-up MRI
CROSSOVER
VISIT 20:
Crossover baseline language assessment
VISITS 21-30:
tDCS+mCILT or sham stimulation+mCILT
VISIT 31 \& 32:
Follow-up language assessment Follow-up MRI
VISIT 33:
6 Week follow-up language assessment
VISIT 34 \& 35:
12-week follow-up language assessment 12-week follow-up MRI
VISIT 36:
24 week follow-up language assessment
- Conditions
- Primary Progressive Aphasia
- Being tested
- Transcranial Direct Current Stimulation (tDCS), Sham tDCS, Modified Contraint-Induced Language Therapy (mCILT)
- Keywords
- non-invasive brain stimulation, transcranial direct current stimulation (tDCS), speech therapy
- Medical subject headings
- Aphasia, Primary Progressive, Communication Disorders
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Transcranial Direct Current Stimulation (tDCS)Device
tDCS is a type of non-invasive brain stimulation in which small electrical currents are applied to the scalp via 2 electrodes. The current, 1.5 mA, is approximately of the same intensity as the current provided by a 9-volt battery. To deliver the current, electrodes that are placed in saline soaked sponges. They will be attached to the left side of your head; they will be held in place with an elastic cap. For both real and sham stimulation the electrodes will be placed on the scalp.
Sham tDCSDevice
tDCS is a type of non-invasive brain stimulation in which small electrical currents are applied to the scalp via 2 electrodes. During sham stimulation, the current, 1.5 mA, will be delivered for a short amount of time and then turn-off. To deliver the current, electrodes that are placed in saline soaked sponges. They will be attached to the left side of your head; they will be held in place with an elastic cap. For both real and sham stimulation the electrodes will be placed on the scalp. Most people cannot tell the difference between real and sham stimulation.
Modified Contraint-Induced Language Therapy (mCILT)Behavioural
Modified constraint-induced language therapy (mCILT) is a behavioral language therapy that invokes use-dependent learning in communicative interactions by requiring spoken output and restricting use of alternative forms of communication, such as gestures, as a substitute for spoken output. Other key elements of CILT include massed practice of goal-directed speech and shaping of desired responses by increasing response demands as participants improve. MCILT differs from traditional constraint-induced language therapy (CILT) in three ways: 1) it will be done as an individual therapy with the examiner in the role of a communication partner; 2) treatment will be delivered in short sessions (1 hour rather than a more typical 3-4 hour session); 3) targeting nouns + semantically related verbs to generate noun + verb phrases in treatment, a modification that may be better suited to addressing syntactic structure.
| Study group | Role | What they receive |
|---|---|---|
| tDCS + CILT | Active comparator | Participants will undergo 10 daily sessions (Monday-Friday, x2 weeks) of tDCS for 20 minutes using a montage in which an anode (1.5 mA) is placed over F7 (left frontotemporal lobe) and the cathode will be place on O1 (left occipital) using the 10-20 EEG mapping system. Subjects will participate in a modified constraint-induced language therapy. Receives: Device: Transcranial Direct Current Stimulation (tDCS); Behavioral: Modified Contraint-Induced Language Therapy (mCILT) |
| Sham tDCS + CILT | Sham comparator | Participants will undergo 10 daily sessions (Monday-Friday, x2 weeks) of sham tDCS for 20 minutes using a montage in which an anode is placed of F7 and cathose is placed over O1. Subjects will participate in a modified constraint-induced language therapy, Receives: Device: Sham tDCS; Behavioral: Modified Contraint-Induced Language Therapy (mCILT) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Western Aphasia Battery Aphasia Quotient (WAB-AQ)
The primary outcome measure will be the change in score on the Western Aphasia Battery Aphasia Quotient (WAB-AQ), a score assessing overall aphasia recovery. Scores can range from 0-100, with higher scores representing better outcomes. 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.
Measured: Baseline to 12 weeks; baseline to 24 weeks when available
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted28 Sep 2020
- Study start1 Dec 2020
- Primary completion1 Jul 2024
- Study completion1 Jul 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Primary Progressive AphasiaStudies of the same condition, open and under way.
- More trials run by University of PennsylvaniaThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- Crossover assignment
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 23 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Pennsylvania
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Roy Hamilton, MS, Principal investigator, University of Pennsylvania
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04566731
- Sponsor's protocol ID
- 843286
- Status last verified
- Oct 2025
- First submitted
- 31 Aug 2020
- Last updated
- 13 Nov 2025
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 13 Nov 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Using Transcranial Direct Current Stimulation to Reveal Mechanisms of Language Loss and to Treat Progressive Aphasia Associated With FTD and Related Dementias
- ClinicalTrials.gov ID
- NCT04566731
- Acronym / sponsor ID
- 843286
- Conditions
- Primary Progressive Aphasia
- Keywords
- non-invasive brain stimulation, transcranial direct current stimulation (tDCS), speech therapy
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 23 participants (actual)
- Lead sponsor
- University of PennsylvaniaUniversity, hospital or other
- Study start
- 1 Dec 2020 (actual)
- Primary completion
- 1 Jul 2024 (actual)
- Study completion
- 1 Jul 2024 (actual)
- First posted
- 28 Sep 2020 (actual)
- Results
- Posted 13 Nov 2025
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a double-blind, sham-controlled, crossover study in which subjects with the non-fluent/agrammatic and semantic variants of primary progressive aphasia (naPPA and svPPA, respectively) will undergo language testing and structural and functional brain imaging before and after receiving 10 semi-consecutive daily sessions of real or sham transcranial direct current stimulation (tDCS) paired with modified constraint-induced language therapy (mCILT). Language testing and brain imaging will be repeated immediately after completion of and up-to 24 weeks following completion of treatment. The investigators will examine changes in language performance induced by tDCS + mCILT compared to sham 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 semantic variants of primary progressive aphasia (naPPA and svPPA, respectively) will undergo language testing and structural and functional brain imaging before and after receiving 10 semi-consecutive daily sessions of real or sham transcranial direct current stimulation (tDCS) paired with modified constraint-induced language therapy (mCILT). Language testing and brain imaging will be repeated immediately after completion of and up-to 24 weeks following completion of treatment.
Subjects with naPPA and svPPA will be randomized to one of two study arms: tDCS+mCILT or sham stimulation+mCILT paired with pre- and post-stimulation imaging and behavioral measures. Equal numbers of subjects with naPPA and svPPA will be randomized to the tDCS + mCILT and sham + mCILT study arms. The study is double-blinded, in that neither the subject nor the study personnel administering tDCS or sham stimulation will know which arm of the study the subject has been randomized into. Study coordinators will administer 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 36 planned visits that will span approximately 12 months. The events of the study visits are described below:
VISIT 1:
Informed consent and screening
VISIT 2:
Baseline MRI
VISIT 3 \& 4:
Baseline language assessment
VISITS 5-14:
tDCS+mCILT OR sham stimulation+mCILT, depending on the study arm to which they had been randomized.
VISIT 15 \& 16:
Follow-up language assessment Follow-up MRI
VISIT 17:
6-Week follow-up language assessment
VISIT 18 \& 19:
12-week follow-up language assessment 12-week follow-up MRI
CROSSOVER
VISIT 20:
Crossover baseline language assessment
VISITS 21-30:
tDCS+mCILT or sham stimulation+mCILT
VISIT 31 \& 32:
Follow-up language assessment Follow-up MRI
VISIT 33:
6 Week follow-up language assessment
VISIT 34 \& 35:
12-week follow-up language assessment 12-week follow-up MRI
VISIT 36:
24 week follow-up language assessment
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Crossover assignment
| Arm | Type | Receives |
|---|---|---|
| tDCS + CILT | Active comparator | Device: Transcranial Direct Current Stimulation (tDCS), Behavioral: Modified Contraint-Induced Language Therapy (mCILT)Participants will undergo 10 daily sessions (Monday-Friday, x2 weeks) of tDCS for 20 minutes using a montage in which an anode (1.5 mA) is placed over F7 (left frontotemporal lobe) and the cathode will be place on O1 (left occipital) using the 10-20 EEG mapping system. Subjects will participate in a modified constraint-induced language therapy. |
| Sham tDCS + CILT | Sham comparator | Device: Sham tDCS, Behavioral: Modified Contraint-Induced Language Therapy (mCILT)Participants will undergo 10 daily sessions (Monday-Friday, x2 weeks) of sham tDCS for 20 minutes using a montage in which an anode is placed of F7 and cathose is placed over O1. Subjects will participate in a modified constraint-induced language therapy, |
Who may qualify
- Ages
- 45 to 80 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Presence of aphasia attributable to the semantic variant (svPPA) or non- fluent/agrammatic variant (naPPA) of Primary Progressive Aphasia.
- Must be a native English speaker
Key exclusion criteria (6 listed)
- History of seizures or unexplained loss of consciousness
- Subjects with metallic objects in the face or head other than dental apparatus such as braces, fillings, and implants.
- Subjects with Pacemakers or ICDs.
- Subjects with previous craniotomy or any breach in the skull
- Subjects with a history of other neurological disorder (stroke, TBI, Parkinson)
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Transcranial Direct Current Stimulation (tDCS)tDCS is a type of non-invasive brain stimulation in which small electrical currents are applied to the scalp via 2 electrodes. The current, 1.5 mA, is approximately of the same intensity as the current provided by a 9-volt battery. To deliver the current, electrodes that are placed in saline soaked sponges. They will be attached to the left side of your head; they will be held in place with an elastic cap. For both real and sham stimulation the electrodes will be placed on the scalp. | Device | tDCS + CILT |
| Sham tDCStDCS is a type of non-invasive brain stimulation in which small electrical currents are applied to the scalp via 2 electrodes. During sham stimulation, the current, 1.5 mA, will be delivered for a short amount of time and then turn-off. To deliver the current, electrodes that are placed in saline soaked sponges. They will be attached to the left side of your head; they will be held in place with an elastic cap. For both real and sham stimulation the electrodes will be placed on the scalp. Most people cannot tell the difference between real and sham stimulation. | Device | Sham tDCS + CILT |
| Modified Contraint-Induced Language Therapy (mCILT)Modified constraint-induced language therapy (mCILT) is a behavioral language therapy that invokes use-dependent learning in communicative interactions by requiring spoken output and restricting use of alternative forms of communication, such as gestures, as a substitute for spoken output. Other key elements of CILT include massed practice of goal-directed speech and shaping of desired responses by increasing response demands as participants improve. MCILT differs from traditional constraint-induced language therapy (CILT) in three ways: 1) it will be done as an individual therapy with the examiner in the role of a communication partner; 2) treatment will be delivered in short sessions (1 hour rather than a more typical 3-4 hour session); 3) targeting nouns + semantically related verbs to generate noun + verb phrases in treatment, a modification that may be better suited to addressing syntactic structure. | Behavioural | Sham tDCS + CILT, tDCS + CILT |
Primary outcome
Western Aphasia Battery Aphasia Quotient (WAB-AQ)
Time frame: Baseline to 12 weeks; baseline to 24 weeks when available
The primary outcome measure will be the change in score on the Western Aphasia Battery Aphasia Quotient (WAB-AQ), a score assessing overall aphasia recovery. Scores can range from 0-100, with higher scores representing better outcomes. 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.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Nov 2025.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Roy Hamilton, MS principal investigator
University of Pennsylvania
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Transcranial Direct Current Stimulation (tDCS) and Modified Contraint-Induced Language Therapy (mCILT) in people with Primary Progressive Aphasia, run by University of Pennsylvania at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 13 Nov 2025. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Yes. Results are posted in the registry (first posted 13 Nov 2025). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Western Aphasia Battery Aphasia Quotient (WAB-AQ) (time frame: Baseline to 12 weeks; baseline to 24 weeks when available). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 13 Nov 2025; AzTrials last refreshed its copy on 27 Oct 2026.