Long Term Effect of Brain Stimulation in PPA

Not Applicable

Recruiting

• Conditions: Primary Progressive Aphasia(PPA)

• Registration Number: NCT07158216
• Lead Sponsor: Hospital San Carlos, Madrid

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.

Study Timeline

• Study First Submitted: 2025-08-28
• Study First Submitted QC: 2025-08-28
• Status Verified: 2025-09
• Last Update Submitted: 2025-09-04
• Study First Posted: 2025-09-05
• Last Update Posted: 2025-09-11
• Study Start: 2025-09-15
• Primary Completion: 2028-12
• Study Completion: 2028-12-01

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 80

Inclusion Criteria

• Diagnosis of PPA according to the current consensus criteria supported by neuroimaging (FDG-PET or MRI) (Gorno-Tempini et al., 2011);
• 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.

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Primary Outcome Measures

Name	Time	Method
Mini-Linguistic State Examination	6 months

Secondary Outcome Measures

Name	Time	Method
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)

Trial Locations

Locations (1)

Hospital Clinico San Carlos; 🇪🇸 Madrid, Spain