Cerebral amyloid angiopathy (CAA) is caused by the accumulation of amyloid-beta (Aβ) in the cerebrovasculature. The glymphatic system is thought to be involved in the clearance of cerebral waste products, including Aβ. Stimulation of the glymphatic system through enhancing deep sleep with low-sodium oxybate (LXB) or inhibition of cortical spreading depolarisations via non-invasive vagus nerve stimulation (nVNS) could potentially increase clearance of Aβ and hence improve disease course.

We will perform a pre-post trial to assess whether treatment with LXB, nVNS or a combination of both interventions can enhance the clearance of Aβ in patients with CAA. A total of 60 participants, 30 with sporadic CAA and 30 with Dutch-type CAA, will be randomly assigned to receive either LXB, nVNS or both interventions, resulting in three groups (20 in each group: LXB, nVNS and both). The study spans 6 months, comprising a 3-month observational phase and a 3-month intervention phase. The primary outcome measure will be the morning levels of Aβ40 and Aβ42 in cerebrospinal fluid (CSF) before and after the intervention. We will assess possible disease progression with (non-)haemorrhagic imaging markers on 7-Tesla MRI at baseline, before and after intervention, as a secondary outcome. Additionally, the activity of the glymphatic system by means of fluid dynamics will be assessed with CSF-Selective T2-weighted Readout with Acceleration and Mobility encoding (CSF-STREAM) on 7-Tesla MRI.

The study was reviewed and approved by the Medical Research Ethics Committee Leiden The Hague Delft (P23.100) on 8 April 2024. The first participant was enrolled on 27 March 2025. Study results will be published in peer-reviewed journals and presented at scientific conferences. Additionally, study updates and results will be shared with participants via our newsletter twice a year.

EU CT number 2023–5 06 128-10-00, Universal Trial Number U1111-1295-1113, ClinicalTrials.gov NCT06421532.

Due to the documented benefits of peripheral resistance training (RT) and inspiratory resistance training, known as inspiratory muscle training (IMT), in patients with cardiovascular disease, both exercise forms are regularly used in cardiac rehabilitation. However, little is known about the haemodynamic responses to different intensities of dynamic RT, isometric RT, and IMT in patients with coronary artery disease (CAD). This study is designed to evaluate and compare the acute haemodynamic responses elicited by different RT and IMT modalities in patients with CAD.

This study design is a prospective, single-centre, randomised crossover trial. A total of 20 participants with CAD will be included. All participants will undergo four different exercise training interventions: IMT, isometric wall squat training (IWS), dynamic leg press training (DLP) and isometric handgrip training (IHG). For each intervention, participants will perform two intensity modalities in randomised order: IMT (low vs high), IWS (low vs moderate), DLP (low vs high) and IHG (low vs moderate). The primary outcomes are the acute exercise-induced haemodynamic responses (esp. systolic blood pressure, pulse rate, stroke volume, cardiac output) across the different exercise training interventions, as well as the changes in haemodynamic responses during the recovery phase for each intervention. Secondary outcomes include changes in tissue oxygen saturation, oxygen saturation, and perceived dyspnoea and exertion. The study period is planned for 2025.

The study has been approved by the Ethics Committee of the German Sport University Cologne (Ethical Approval Code: 209/24). The findings will be disseminated through international peer-reviewed publications. This study is supported by the Alexander von Humboldt Foundation via the partnership with the Coordenacão de Aperfeicoamento de Pessoal de Nível Superior (CAPES)(CAPES-Humboldt Research Fellowship for Experienced Researchers) and by research funding from Edwards Lifesciences LLC (Limited Liability Company).

German Clinical Trials Register DRKS00035668.