Long-term brain stimulation for primary progressive aphasia

Long-term Effect of Transcranial Magnetic Stimulation and Transcranial Electrical Stimulation in Primary Progressive Aphasia: Randomized, Double-blind Clinical Trial (RECONNECT-PLUS)

This trial will test whether two non-invasive brain stimulation methods (TMS and tDCS), alone or combined and paired with language therapy, can slow or improve language decline over six months in people with primary progressive aphasia.

Quick facts

• Phase: Not applicable
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Hospital San Carlos, Madrid (Academic / other)
• Locations: 1 site (Madrid)
• Trial ID: NCT07158216 on ClinicalTrials.gov

What this trial studies

Participants with a consensus diagnosis of primary progressive aphasia will be randomized to receive intermittent theta-burst TMS, excitatory tDCS, combined TMS+tDCS, or sham stimulation, with all groups receiving the same language therapy. Stimulation targets the left dorsolateral prefrontal cortex using neuronavigation, and language therapy follows a lexical retrieval cascade protocol delivered after each stimulation session. Outcomes will track language performance and progression over a six-month period to compare active modalities against sham. The protocol is interventional and focused on non-invasive neuromodulation paired with standardized speech-language therapy.

Who should consider this trial

Good fit: Ideal candidates are people diagnosed with one of the three PPA variants per consensus criteria, with language impairment as the main deficit, a Clinical Dementia Rating of 1 or less, and supportive neuroimaging (MRI or FDG-PET).

Not a fit: People with alternative causes of language impairment, a history of epilepsy, focal epileptiform EEG findings, contraindications to brain stimulation, or more advanced dementia are unlikely to benefit or may be excluded.

Why it matters

Potential benefit: If successful, this approach could slow language decline or improve language function in people with PPA and offer a non-invasive adjunct to speech therapy.

How similar studies have performed: Several small trials have reported short-term language improvements with TMS or tDCS in PPA, but long-term effects and combined TMS+tDCS protocols remain largely unproven.

Eligibility criteria

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.

Where this trial is running

Madrid

• Hospital Clinico San Carlos — Madrid, Spain (Recruiting)

Study contacts

• Study coordinator: Jordi Matias-Guiu, PhD MD

Conditions Primary Progressive Aphasia; Primary progressive aphasia; Frontotemporal dementia; Alzheimer' s disease; Brain stimulation; Transcranial Magnetic Stimulation; Transcranial direct current stimulation