{
  "abstract": "Introduction Primary progressive aphasia (PPA) is a neurodegenerative syndrome associated with Alzheimer’s disease and frontotemporal degeneration. Non-invasive brain stimulation (NIBS) is a promising treatment, especially associated with language therapy, but comparative efficacy and long-term effects between the different techniques (transcranial direct current stimulation (tDCS) and transcranial magnetic stimulation (TMS)) remain unknown. The present study aims to investigate the effects of non-invasive brain stimulation, alone or associated (tDCS/TMS/tDCS plus TMS) combined with language therapy delivered during a period of 6 months, in the progression of language impairment in PPA, compared with sham stimulation combined with language therapy.Methods and analysis The study is a randomised, double-blinded, parallel, sham-controlled clinical trial. Patients with PPA in early stages (global Clinical Dementia Rating equal to or less than 1) are eligible. They are to be randomised to one of the four treatment arms of the study (active tDCS-active TMS, active tDCS-sham TMS, sham tDCS-active TMS, sham tDCS-sham TMS). All patients will receive language therapy immediately after each session of NIBS, for 6 months. The primary outcome is the Mini-Linguistic State Examination. The secondary outcomes are naming of trained items, Addenbrooke’s Cognitive Examination, Interview for Deterioration in Daily Living Activities, Clinical Dementia Rating including behaviour and language domains, Neuropsychiatric Inventory and regional brain metabolism. Exploratory substudies will be conducted including blood biomarkers, quantitative electroencephalography and spontaneous speech assessment.Ethics and dissemination The study is registered (ClinicalTrials.gov: NCT07158216) and approved by the Ethics Committee of the Hospital Clinico San Carlos (code 25/309-IC_P_CE). Patients will be enrolled after signing an informed consent form. Study outcomes will be disseminated through presentations at scientific conferences, publications in peer-reviewed journals and other academic forums.Trial registration number NCT07158216.",
  "authors": [
    {
      "affiliations": [
        "Department of Neurology, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Universidad Complutense de Madrid, Hospital Clinico San Carlos, Madrid, Spain"
      ],
      "name": "Lucía Fernández-Romero"
    },
    {
      "affiliations": [
        "Department of Neurology, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Universidad Complutense de Madrid, Hospital Clinico San Carlos, Madrid, Spain"
      ],
      "name": "María Díez-Cirarda"
    },
    {
      "affiliations": [
        "Department of Neurology, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Universidad Complutense de Madrid, Hospital Clinico San Carlos, Madrid, Spain"
      ],
      "name": "Cristina Delgado-Alonso"
    },
    {
      "affiliations": [
        "Department of Nuclear Medicine, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Universidad Complutense de Madrid, Hospital Clinico San Carlos, Madrid, Spain"
      ],
      "name": "Maria Nieves Cabrera-Martin"
    },
    {
      "affiliations": [
        "Institute of Research and Biomedical Innovation of Cadiz (INiBICA), University of Cadiz, Cádiz, Spain"
      ],
      "name": "Javier J González-Rosa"
    },
    {
      "affiliations": [
        "Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Unidad de Investigación Clínica y Ensayos Clínicos (UICEC), Madrid, Spain"
      ],
      "name": "Carmen Sanz-Nieto"
    },
    {
      "affiliations": [
        "Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Unidad de Investigación Clínica y Ensayos Clínicos (UICEC), Madrid, Spain"
      ],
      "name": "Natalia Pérez-Macías"
    },
    {
      "affiliations": [
        "Department of Clinical Neurophysiology, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Hospital Clinico San Carlos, Madrid, Spain"
      ],
      "name": "Paloma Balugo"
    },
    {
      "affiliations": [
        "Department of Radiology, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Universidad Complutense de Madrid, Madrid, Spain"
      ],
      "name": "Natividad Gómez-Ruiz"
    },
    {
      "affiliations": [
        "Department of Neurology, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Universidad Complutense de Madrid, Hospital Clinico San Carlos, Madrid, Spain"
      ],
      "name": "Jorge Matias-Guiu"
    },
    {
      "affiliations": [
        "Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Unidad de Investigación Clínica y Ensayos Clínicos (UICEC), Madrid, Spain",
        "Department of Pharmacology & Toxicology, School of Medicine, Universidad Complutense de Madrid, Madrid, Spain",
        "Department of Clinical Pharmacology, Hospital Clínico San Carlos, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Madrid, Spain"
      ],
      "name": "Antonio Portolés-Pérez"
    },
    {
      "affiliations": [
        "Department of Neurology, Instituto de Investigación Sanitaria del Hospital Clínico San Carlos (IdISSC), Universidad Complutense de Madrid, Hospital Clinico San Carlos, Madrid, Spain"
      ],
      "name": "Jordi A Matias-Guiu"
    }
  ],
  "title": "Long-term effect of transcranial magnetic stimulation and transcranial electrical stimulation in primary progressive aphasia: study protocol for a randomised, double-blind clinical trial (RECONNECT-PLUS)",
  "uid": "b0670f74-58e4-5984-abd4-1a2c6d858bad"
}