Tests brain stimulation with speech therapy for primary progressive aphasia
Tests magnetic brain stimulation plus speech therapy in people with primary progressive aphasia.
Plain-language title generated from the registry record
Registry title: Targeted Transcranial Magnetic Stimulation to Improve Language and Speech in Patients With Primary Progressive Aphasia
Key facts
- Where
- Milan, ItalySee the site
Could this be for you?
Answer for yourself. This is not a decision: only the study team can say whether you can take part.
- Are you between 40 and 85 years old?
Source: NCT06921265, who can take part
Where in Italy
- San Raffaele Neurotech HubMilan, ItalyNo longer taking part
Questions to ask the study team
- How often do I need to come in, and for how long each time?
- Are travel costs paid?
- Can I keep my own doctor?
- What happens if I want to stop?
Trial details
- Who runs it
- IRCCS San Raffaele
- Trial code
- NCT06921265
- Record updated
- 20 May 2026
- Original description
This is a monocenter randomized controlled clinical trial with cross-over arm - assessor blinded. The aims is investigating the effects of the speech language therapy (SLT) alone vs SLT + non-invasive brain stimulation (STIM), using canonic repetitive Transcranial Magnetic Stimulation (rTMS), on speech and language, clinical, neuropsychological, neuroimaging, neurophysiology, and blood features in patients with PPA.Read full original descriptionShow less
Tailored Neuromodulation Intervention to Enhance Speech and Language Training in Patients With Primary Progressive Aphasia: EEG and MRI Targeted Transcranial Magnetic Stimulation
This is a monocenter randomized controlled clinical trial with cross-over arm - assessor blinded. The aims is investigating the effects of the speech language therapy (SLT) alone vs SLT + non-invasive brain stimulation (STIM), using canonic repetitive Transcranial Magnetic Stimulation (rTMS), on speech and language, clinical, neuropsychological, neuroimaging, neurophysiology, and blood features in patients with PPA.
The trial will include 45 participants suffering from semantic (svPPA), logopenic (lvPPA) or nonfluent (nfvPPA) variants of Primary Progressive Aphasia (PPA) and 30 healthy controls.
At baseline (T0) patients will undergo in-depth clinical, neuropsychological and language assessment, structural and functional magnetic resonance imaging (MRI) scan, electroencephalography (EEG) recording, functional Near Infrared Spectroscopy (fNiRS) scans, and blood sample.
PPA patients will be randomized into 2 training groups: the speech language therapy (SLT) group and the SLT + STIM (standard rTMS group or targeted rTMS).
The SLT will consist of an online intervention performed through a web-based platform. The training will be tailored to each PPA variant. svPPA and lvPPA will undergo the lexical retrieval cascade (LRC) treatment, while nfvPPA will undergo the Video-implemented Script Training (VISTA).
The SLT+ STIM group will perform the same SLT combined with non-invasive stimulation with a cross-over design: canonic repetitive Transcranial Magnetic Stimulation (rTMS) on the left dorsolateral prefrontal cortex (DLPFC) or targeted rTMS in which the site and the protocol of stimulation will be defined based on single-subject EEG combined with functional MRI (EEG+fMRI).
This design will aid in determining not only whether non-invasive stimulation can enhance clinical outcomes, but also which non-invasive stimulation is the best to improve results.
The SLT training of the SLT group will consist of 2 cycles of training lasting 1 (rest) + 5 (training) weeks, 3 times per week, 1 hour each session, separated by a 12-week washout period.
The SLT + standard or targeted STIM groups will undergo 2 cycles of 6-week training, separated by a 12-week washout period with a cross-over design: half of subjects will first receive 6-week SLT training associated with DLPFC rTMS followed by 6-week SLT associated with targeted rTMS, while the other half will follow the reverse order, according to a randomization procedure.
After the training (i.e., 6-week visit [W6] and 24-week visit [W24]), PPA patients will be re-evaluated through neurological, language, neuroimaging/neurophysiology assessments, and blood sample.
Evaluations will be also repeated at the 18-week (W18) after the wash-out and before the second cycle of treatment, as well as at 36-week (W36) and 48-week (W48) follow-up visits to assess maintenance of results. MRI and blood sample will be repeated at all visits but W18 and W36. The comprehensive neuropsychological assessment will be repeated at W48 only.
30 healthy controls will also be recruited among the spouses of patients, by word of mouth or through flyers and project awareness campaigns. They will undergo the same assessments administered to PPA patients at T0 (neurological, neuropsychological/language assessments, neuroimaging/neurophysiology, and blood sample).
Hypothesis:
1. Patients with PPA who receive a combination of SLT and rTMS will exhibit greater clinical improvement compared to those receiving SLT alone. 2. Choosing the rTMS approach and stimulation site based on individualized MRI and EEG characterization will be more effective as compared to using the standard rTMS approaches described by the literature. 3. The integration of specific clinical, cognitive, language, neuroimaging, neurophysiological, and blood features will enable the prediction of individual responses to SLT and rTMS, facilitating the development of optimized, personalized treatment plans for PPA.
Inclusion: Clinical and imaging-supported diagnosis of any variant of PPA (svPPA, lvPPA, nfvPPA) according to international diagnostic criteria (Gorno- Tempini et al., 2011); Age range: 40-85; MMSE>15; Native Italian Speaker; Right handedness; Stable pharmacological treatment of at least 4 weeks and without any change during the observation period (48 weeks); Oral and written informed consent to study participation; Sex-matched and age-matched (age range: mean age of PPA years ± 15 years); MMSE>27; Native Italian Speaker; Right handedness; Oral and written informed consent to study participation.
Exclusion: Concomitant participation to other pharmacological and non pharmacological studies; Any major systemic, psychiatric, neurological, and visual disturbance; Medical conditions or substance abuse that could interfere with cognition; Brain damage at routine MRI, including extensive cerebrovascular disorders; Traumatic or surgical wounds that could determine a risk of infection in the site of non-invasive stimulation; Known history of epilepsy (due to small risk of seizure induction from rTMS in epileptic patients; Any major systemic, psychiatric, neurological, and visual disturbance; Medical conditions or substance abuse that could interfere with cognition; Brain damage at routine MRI, including extensive cerebrovascular disorders; Hypoacusis or severe visual deficits; Pacemaker and/or other implanted neurostimulation devices in the head/neck district; (Other) Contraindications to undergoing MRI examination; Denied oral and written informed consent to study participation; Inability to repeat multisyllabic words (4 syllables); Scalp alterations that could determine the spread of excessive current from the device; Hypoacusis or severe visual deficits; Pacemaker and/or other implanted neurostimulation devices in the head/neck district; (Other) Contraindications to undergoing MRI examination; Denied oral and written informed consent to study participation.