Transcranial Magnetic Stimulation in Primary Progressive Aphasia

Study Overview
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Brief Summary
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Primary progressive aphasia (PPA) is a clinical syndrome characterized by the neurodegeneration of language brain systems. Three main clinical variants are currently recorgnized (nonfluent, semantic, and logopenic PPA). Nowadays, there are no effective treatments for this disorder. Transcranial Magnetic Stimulation (TMS) is a technique based on the principle of electromagnetic induction of an electric field in the brain. It has been used as a non-invasive therapy in different disorders, such as depression, bipolar disorder, Parkinson's disease, and in the rehabilitation of post-stroke aphasia. Recent studies have shown how repetitive TMS improved language characteristics in Alzheimer's disease, and there are initial data in patients with PPA. This research project investigates the effect of repetitive TMS in patients with PPA. Investigators will perform a personalized TMS treatment for each patient (brain region, type of stimulation/inhibition, etc.), according to the specific characteristics of each patient and with the final aim to generate a computational model.

Official Title
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Transcranial Magnetic Stimulation in Primary Progressive Aphasia

Conditions
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Primary Progressive Aphasia

Intervention / Treatment
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* Device: Transcranial Magnetic Stimulation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Must be clinically diagnosed of PPA according to current diagnostic criteria (Gorno-Tempini et al. 2011) with PET-FDG confirmation. Clinical Dementia Rating 0-1. Exclusion Criteria: Contraindications for TMS or MRI History of epilepsy Pregnancy Other language disorder previous to the diagnosis of PPA Neuroimaging not suggestive of PPA

Ages Eligible for Study
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Minimum Age: 45 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Repetitive TMS (estimulation)<br> | Device: Transcranial Magnetic Stimulation<br>* Stimulation or inhibition using TMS will be delivered guided by a neuronavigator system in different brain regions.<br>|
| Active Comparator: Repetitive TMS (inhibition)<br> | Device: Transcranial Magnetic Stimulation<br>* Stimulation or inhibition using TMS will be delivered guided by a neuronavigator system in different brain regions.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in spontaneous speech (main primary endpoint) | Picture and story description task | 2 months (at baseline and at the end of the treatment) | 
| Changes in oral naming | Object naming test | 2 months | 
| Changes in reading | Story and words reading test | 2 months | 
| Changes in repetition | Non-words and sentence repetition task | 2 months (at baseline and at the end of the treatment) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes in brain metabolism | Brain metabolism measured using 18F-FDG-PET | 2 months (at baseline and at the end of the treatment) | 
| Changes in clinical impression of change | Patient's clinical impression of change (from 0 to 10) | 2 months (at baseline and at the end of the treatment) | 
| Changes in brain cortical electrical activity | Changes in the brain cortical electrical activity measured using quantitative electroencephalography (EEG) | 2 months (at baseline and at the end of the treatment) | 
| Changes in global cognition | Addenbrooke's Cognitive Examination III | 2 months (at baseline and at the end of the study) | 
| Changes in clinical impression of change | Caregiver's clinical impression of change (from 0 to 10) | 2 months |