Primary Progressive Aphasia(PPA)
Conditions
Keywords
Primary progressive aphasia, Frontotemporal dementia, Alzheimer's disease, Brain stimulation, Transcranial Magnetic Stimulation, Transcranial direct current stimulation, Transcranial electrical stimulation
Brief summary
The goal of this clinical trial is to investigate the effect of non-invasive brain stimulation techniques in the progression of primary progressive aphasia for 6 months. We will compare three modalities of brain stimulation (TMS, tDCS, TMS+tDCS) against sham stimulation. All patients will receive also language therapy.
Detailed description
Transcranial Magnetic Stimulation will follow an intermitent theta-burst protocol targetting the left dorsolateral prefrontal cortex. Transcranial electrical stimulation will also follow an excitatory protocol over the same region. All brain stimulation procedures will be conducted under neuronavigation. Language therapy will follow the lexical retrieval cascade protocol and will be conducted after each brain stimulation session.
Interventions
DEVICETMS
Active TMS + sham tDCS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks)
DEVICEtDCS
sham TMS + active tDCS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks)
DEVICESham TMS
Sham TMS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks)
DEVICESham tDCS
Sham tDCS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks)
Sponsors
Hospital San Carlos, Madrid
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Both outcome assessors and participants will be blinded to the assigned treatment. Only the technicians administering TMS will be aware of the brain stimulation assignment.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
* Diagnosis of PPA according to the current consensus criteria proposed by Gorno-Tempini et al., 2011), based on the presence of progressive language impairment as the most prominent and primary cause of functional decline and the exclusion of other medical, psychiatric, or non-neurodegenerative causes,a s well as early prominent memory, visuoperceptual or behavioral disturbances; * Diagnosis of one of the three variants of PPA (non-fluent, semantic, or logopenic) according to the consensus criteria (Gorno-Tempini et al., 2011), based on the language profile and supported by neuroimaging (FDG-PET or MRI). * Clinical Dementia Rating scale equal or less than 1; * The language impairment is the main neurological deficit for the patient.
Exclusion criteria
* Patient diagnosed with a condition other than PPA that could cause language impairment; * History of epilepsy or presence of focal epileptiform pathology on EEG recording; ·Contraindications related to the treatments or procedures to be used (TMS and tDCS), such as ferromagnetic material, pregnancy, or breastfeeding; * Terminal illness or active malignancy; * Alcohol or substance abuse within the past year; * Major psychiatric disorders (schizophrenia, schizoaffective disorders, bipolar disorder, obsessive-compulsive disorder, or personality disorders); * Absolute inability to communicate (mutism), or poor command of the language that, in the investigator's judgment, would prevent participation in the study; * Severity of PPA that prevents participation in interventions or assessments at the time of inclusion; * Participation in another clinical trial within the previous 4 months; * Chronic use of medications that could affect study outcomes; * Antiepileptic drugs: allowed if on stable doses for at least 3 months before inclusion. If needed during the study due to seizure occurrence, they may be added; * Diazepam and derivatives: permitted only if on stable doses for at least 3 months before inclusion. Dose adjustments during the study are allowed; * Donepezil, Galantamine, Rivastigmine, and Memantine: allowed if on stable doses for at least 3 months before inclusion; * SSRIs (Selective Serotonin Reuptake Inhibitors): permitted only if on stable doses for at least 3 months prior to inclusion. If necessary during the study, they may be added; * Medications that may lower the seizure threshold (e.g., tricyclic antidepressants, antipsychotics): allowed if on stable doses for at least 3 months before inclusion.
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Mini-Linguistic State Examination | 6 months |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Naming of trained words | 6 monhts | It will be evaluated using a list of 261 words from eight semantic categories (animals, food, objects, places, furniture, clothing, transportation, and body parts) |
| ACE-III | 6 months | General cognition |
| Interview for Deterioration in Daily Living Activities in Dementia (IDDD) | 6 months | Functional activities |
| Communicative Effectiveness Index (CETI) | 6 months | Functional communication questionnaire |
| CDR(R) plus NACC FTLD-SB | 6 months | Clinical Dementia Rating |
| Neuropsychiatric Inventory (NPI) | 6 months | Neuropsychiatric symptoms |
| FDG-PET imaging | 6 months | Regional brain metabolism in a region of interest capturing a large part of the left hemisphere and associated with clinical decline in PPA (Fernandez-Romero et al. 2025) |
Countries
Spain
Contacts
CONTACTJordi Matias-Guiu, PhD MD
Outcome results
None listed