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.

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.

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.

NCT07158216.

In non-intubated patients, symptomatic treatment of hypoxaemic respiratory failure is still debated, with different options: (1) standard oxygen therapy (SOT), (2) high-flow nasal cannula oxygen therapy (HFNC) and (3) non-invasive ventilation (NIV). The objective of this study is to compare the effects of HFNC and NIV on lung volumes assessed by CT scan to allow a better understanding of their effectiveness.

The HONIVAH study (High-flow Oxygen therapy and Non-Invasive ventilation on lung Volumes and on upper Airway in Hypoxemic critically ill patients) is an investigator-initiated, prospective, single-centre, physiological, randomised, parallel-group, unblinded trial with an electronic system-based randomisation. Patients with hypoxaemic respiratory failure, defined as the need for SOT flow ≥3 L/min to maintain a pulsed oxygen saturation ≥95%, and a CT scan prescribed by the physician in charge of the patient, will be randomly assigned to the HFNC group or the NIV group. Two inspiratory thoracic CT scans will be performed, one with SOT as part of the routine patient management and a second thoracic CT scan with HFNC or NIV, depending on the allocation group. The primary outcome is the comparison of the relative variation in ‘poorly aerated’ and ‘non-aerated’ lung volumes before and after the intervention between the HFNC group and NIV group, assessed by thoracic CT scan. Secondary outcomes included the variation in tracheal cross-sectional upper airway area, lung volumes, gas exchange and patient comfort.

The study project has been approved by the appropriate ethics committee (Comité de Protection des Personnes Sud-Ouest et Outre-mer 1, France, 2022-A02458-35). Informed consent is required. The results will be submitted for publication in a peer-reviewed journal and presented at one or more scientific conferences.

ClinicalTrials.gov identifier: NCT05643911.