Primary Progressive Aphasia
Conditions
Keywords
non-invasive brain stimulation, transcranial direct current stimulation (tDCS), speech therapy
Brief 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 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
Interventions
DEVICETranscranial 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.
DEVICESham tDCS
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.
BEHAVIORALModified 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.
Sponsors
University of Pennsylvania
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
TREATMENT
Masking
TRIPLE (Subject, Caregiver, Investigator)
Intervention model description
Crossover assignment
Eligibility
Sex/Gender
ALL
Age
45 Years to 80 Years
Healthy volunteers
No
Inclusion criteria
* 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
Exclusion criteria
* 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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Western Aphasia Battery Aphasia Quotient (WAB-AQ) | 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. |
Countries
United States
Participant flow
Recruitment details
Participants were recruited from July 2020-July 2024 from the Hospital of the University of Pennsylvania and surrounding Philadelphia area medical centers.
Pre-assignment details
A total of 3 participants did not qualify at the time of enrollment due to low MMSE scores (2) and diagnosis change that no longer met our PPA criteria (1). A total of 2 participants dropped out of the study before they were randomized due to travel concerns.
Participants by arm
| Arm | Count |
|---|---|
| tDCS + CILT First, Then Sham + CILT 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 simultaneously participate in a modified constraint-induced language therapy.
Participants will then crossover to the Sham tDCS condition. | 10 |
| Sham tDCS + CILT First, Then tDCS + CILT 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 cathode is placed over O1. During sham stimulation, the current, 1.5 mA, will be delivered for a short amount of time (about 30 seconds) and then turn-off. Most people cannot tell the difference between real and sham stimulation. Subjects will simultaneously participate in a modified constraint-induced language therapy.
Participants will then crossover into the tDCS condition. | 8 |
| Total | 18 |
Baseline characteristics
| Characteristic | tDCS + CILT First, Then Sham + CILT | Total | Sham tDCS + CILT First, Then tDCS + CILT |
|---|---|---|---|
| Age, Continuous | 67.5 years STANDARD_DEVIATION 5.89 | 67.7 years STANDARD_DEVIATION 6.24 | 68 years STANDARD_DEVIATION 6.65 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 10 Participants | 18 Participants | 8 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) American Indian or Alaska Native | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Asian | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Black or African American | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) More than one race | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Native Hawaiian or Other Pacific Islander | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) Unknown or Not Reported | 0 Participants | 0 Participants | 0 Participants |
| Race (NIH/OMB) White | 10 Participants | 18 Participants | 8 Participants |
| Sex: Female, Male Female | 6 Participants | 11 Participants | 5 Participants |
| Sex: Female, Male Male | 4 Participants | 7 Participants | 3 Participants |
| Western Aphasia Battery (WAB-AQ) Score | 74.9 scores on a scale STANDARD_DEVIATION 12.84 | 76.3 scores on a scale STANDARD_DEVIATION 13.2 | 78.0 scores on a scale STANDARD_DEVIATION 13.48 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 18 | 0 / 18 |
| other Total, other adverse events | 4 / 18 | 3 / 18 |
| serious Total, serious adverse events | 1 / 18 | 1 / 18 |
Outcome results
Primary
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.
Time frame: Baseline to 12 weeks; baseline to 24 weeks when available
Population: 24 week follow-up data are not available for individuals randomized to the tDCS + CILT first, then Sham tDCS + CILT group because there is no 24 week follow-up for the first arm. 24 week follow-up data are not available for individuals randomized to the Sham tDCS + CILT first, then tDCS + CILT group because there is no 24 week follow-up for the first arm.
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| tDCS + CILT First, Then Sham tDCS + CILT | Western Aphasia Battery Aphasia Quotient (WAB-AQ) | tDCS: Baseline | 74.4 scores on a scale | Standard Deviation 14.2 |
| tDCS + CILT First, Then Sham tDCS + CILT | Western Aphasia Battery Aphasia Quotient (WAB-AQ) | tDCS: 12 Week Follow-up | 72.5 scores on a scale | Standard Deviation 15.9 |
| tDCS + CILT First, Then Sham tDCS + CILT | Western Aphasia Battery Aphasia Quotient (WAB-AQ) | Sham: Baseline | 72.5 scores on a scale | Standard Deviation 15.9 |
| tDCS + CILT First, Then Sham tDCS + CILT | Western Aphasia Battery Aphasia Quotient (WAB-AQ) | Sham: 12 Week Follow-up | 72.2 scores on a scale | Standard Deviation 17.6 |
| tDCS + CILT First, Then Sham tDCS + CILT | Western Aphasia Battery Aphasia Quotient (WAB-AQ) | Sham: 24 Week Follow-up | 67.5 scores on a scale | Standard Deviation 21.1 |
| Sham tDCS + CILT First, Then tDCS + CILT | Western Aphasia Battery Aphasia Quotient (WAB-AQ) | Sham: Baseline | 80.7 scores on a scale | Standard Deviation 9 |
| Sham tDCS + CILT First, Then tDCS + CILT | Western Aphasia Battery Aphasia Quotient (WAB-AQ) | Active: 24 Week Follow-up | 75.0 scores on a scale | Standard Deviation 15.9 |
| Sham tDCS + CILT First, Then tDCS + CILT | Western Aphasia Battery Aphasia Quotient (WAB-AQ) | tDCS: Baseline | 76.5 scores on a scale | Standard Deviation 12.5 |
| Sham tDCS + CILT First, Then tDCS + CILT | Western Aphasia Battery Aphasia Quotient (WAB-AQ) | tDCS: 12 Week Follow-up | 76.0 scores on a scale | Standard Deviation 15.9 |
| Sham tDCS + CILT First, Then tDCS + CILT | Western Aphasia Battery Aphasia Quotient (WAB-AQ) | Sham: 12 Week Follow-up | 76.5 scores on a scale | Standard Deviation 12.5 |
p-value: <0.05ANOVA