Long Term Effect of Brain Stimulation in PPA

Official title

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

Overview

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.

Interventions

• Device TMS
  Active TMS + sham tDCS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks)
• Device tDCS
  sham TMS + active tDCS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks)
• Device Sham TMS
  Sham TMS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks)
• Device Sham tDCS
  Sham tDCS. All patients will receive language therapy immediately after brain stimulation. The period of treatment will be 6 months, comprising 10 consecutive sessions in two weeks (intensive period) followed by once per week (maintenance period of 22 weeks)

Primary outcome measures

• Mini-Linguistic State Examination [Time frame: 6 months]

Secondary outcome measures (7)

• Naming of trained words [Time frame: 6 monhts]
• ACE-III [Time frame: 6 months]
• Interview for Deterioration in Daily Living Activities in Dementia (IDDD) [Time frame: 6 months]
• Communicative Effectiveness Index (CETI) [Time frame: 6 months]
• CDR(R) plus NACC FTLD-SB [Time frame: 6 months]
• Neuropsychiatric Inventory (NPI) [Time frame: 6 months]
• FDG-PET imaging [Time frame: 6 months]

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.

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Parallel assignment

Masking

Quadruple blind

Primary purpose

Treatment

Study locations

Spain · 1 center

• Hospital Clinico San Carlos — Madrid

Publications

• Fernandez-Romero L, Diez-Cirarda M, Delgado-Alonso C, Cabrera-Martin MN, Gonzalez-Rosa JJ, Sanz-Nieto C, Perez-Macias N, Balugo P, Gomez-Ruiz N, Matias-Guiu J, Portoles-Perez A, Matias-Guiu JA. 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). B PMID 42161537

Identifiers

NCT: NCT07158216 · Hospital Clinico San Carlos

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗