Clinical trials

The main goal of the project is provision of a global registry for mitochondrial disorders to harmonize previous national registries, enable world-wide participation and facilitate natural history studies, definition of outcome measures and conduction of clinical trials.

Tricuspid regurgitation (TR) is a severe and highly prevalent disease that leads to right-sided heart failure. The severity of TR is associated with increasing morbidity and mortality. While severe TR and right-sided heart failure have an impact on the quality of life and prognosis of the individual patient, repeat heart failure hospitalizations challenge limited hospital resources on an institutional level and stress the medical health care system on an economic level. Transcatheter valve interventions (TTVI) including transcatheter tricuspid edge-to-edge repair (T-TEER) and transcather tricuspid valve replacement (TTVR) have been established as effective techniques to safely reduce TR severity in many patients leading to significant improvements in quality-of-life and potential reduction of heart failure hospitalizations. However, the rate of heart failure hospitalizations remains elevated, despite technically successful TTVI. Accordingly, heart failure hospitalizations occur in approximately 15-20% of patients and often result in complicated and prolonged in-hospital treatments. Therefore, optimization of the heart failure management and reduction of post-procedural heart failure hospitalizations are unmet needs in patients after TTVI. Implantable pulmonary artery (PA) pressure sensing (IPAPS) is a novel strategy to improve heart failure management and to reduce heart failure hospitalizations. Continuous PA pressure monitoring provides an early indication of worsening heart failure trends and allows for the guidance of medical management to prevent unplanned hospitalizations. So far, this technology has been predominantly studied in patients with left-sided heart failure. The performance of PA pressure monitoring in right-sided heart failure is understudied. Also, the changes of PA pressure levels in response to TTVI has not yet been investigated. Heart failure hospitalizations in patients with right-sided heart failure are caused by gradual fluid overload resulting in shortness of breath, weight gain, peripheral edema, and ascites. Fluid overload will lead to a simultaneous increase of PA pressure, and therefore, may also be identified early by IPAPS in right-sided heart failure patients. The Cordella PA Sensor System has been designed for multi-parametric heart failure telemonitoring including PA pressure and other vital signs. In clinical trials, the Cordella PA Sensor System demonstrated a significantly lower heart failure hospitalization and all-cause mortality event rate in NYHA class III heart failure patients, when compared to historical PA pressure studies. IPAPS was associated with significant improvements in quality-of-life metrics, while complication rates were low. The Cordella PA Sensor System is expected to receive CE-marking in 2025. The proposed study will be initiated after CE-mark approval, so that all patients will be treated with CE-marked devices and on-label. In this study we will assess the applicability of PA pressure monitoring using the Cordella Sensor device in patients with severe TR undergoing T-TEER or TTVR (n=30 patients). Included patients will undergo right-heart catheterization for evaluation of TR as indicated by clinical routine practice before TTVI. During right heart catheterization, patients receive implantation of the Cordella Sensor device. Thereafter, PA pressure will be monitored for approximately 4 weeks prior to TTVI. Subsequently, patients undergo T-TEER or TTVR as indicated and recommended by the heart team. PA pressure telemonitoring will be continued after TTVI. The change in PA pressure before TTVI compared to the first month after TTVI will be reported as primary endpoint in this pilot study. The performance of the Cordella PA Sensor System in right-sided heart failure patients for remote heart failure monitoring will be assessed over a 12-month follow-up period as the main secondary endpoint. The concept of IPAPS has the potential to significantly improve the post-procedural heart failure management in patients after TTVI. The proposed pilot study will serve as base for the development of a larger clinical trial evaluating the concept of PA telemonitoring for improving outcomes in patients with severe tricuspid regurgitation and right-sided heart failure. In an adjunct feasibility study, an implantable pulmonary artery pressure sensor (IPAPS) will be implanted off-label in the hepatic vein to evaluate a sensitive heart failure monitoring strategy in patients with right-sided heart failure (n = 15).

SOPHIE is a prospective, multicentre, observational cohort study aiming to enrol 2,000 CHF patients. Baseline assessments include validated PA questionnaires (GPAQ, IPAQ, KCCQ) and seven-day step counts from commercially available pedometer devices. Follow-up is conducted every six months via telephone, repeating PA assessments and recording cardiovascular events, hospitalisations, and patient-reported outcomes.

Background: The radiological follow-up of diffuse gliomas is challenged by the difficult distinction of true progression from treatment-related changes. To this end, the Response Assessment in Neuro-Oncology (RANO) Working Group has issued specific recommendation for the standardized evaluation of magnetic resonance imaging (MRI). In addition, positron emission tomography (PET) using radiolabeled amino acids allows for the delineation of metabolically active tumor regions in brain tumors, and guidelines for PET-based response assessment have been recently proposed (PET RANO 1.0). However, well-annotated data on longitudinal PET alterations before and during treatment and follow-up are missing in isocitrate dehydrogenase (IDH)-mutant gliomas, particularly as tumor entities defined by IDH mutations have been established only recently and data on PET imaging mainly rely on previous brain tumor classification frameworks. Aims: This bicentric, prospective, observational study aims to collect data on imaging-based disease monitoring in patients with IDH-mutant gliomas. Specifically, this study aims to investigate longitudinal changes of amino acid PET tracer uptake during treatment in IDH-mutant gliomas and to evaluate the correlation between amino acid PET uptake at baseline and response to postoperative standard of care treatment. Patient cohort/methods: Adult (age ≥ 18 years) patients diagnosed and/or treated at the Medical University of Vienna (Vienna, Austria) or the LMU Hospital Munich (Munich, Germany) with histologically verified diffuse IDH-mutant glioma (oligodendroglioma, astrocytoma of all grades) and PET imaging for routine follow-up before, during and after treatment will be included. Clinical and imaging data will be collected in a standardized manner and correlated with treatment response. Primary endpoint is progression-free survival (PFS) according to RANO 2.0 criteria, secondary endpoints include PFS according to PET-RANO 1.0 criteria, time to next intervention (TTNI) and overall survival (OS). Originality/relevance: This study will generate data that will inform future response assessment frameworks and the design of future clinical trials in IDH-mutant glioma.

The aim is to use AI to assist surgeons in analyzing CLSM tissue slide images obtained during BCC surgeries with the aim to integrate it in real time. We plan to use AI to analyze CLSM images of BCCs and distinguish between tumor tissue, inflammatory tissue, and non-tumor/non-inflammatory tissue. This approach would provide surgeons with real-time feedback and automated image analysis, leading to a more targeted and efficient approach to tissue analysis. By improving the accuracy and speed of tissue analysis, our proposal could ultimately improve operative patient outcomes and benefit healthcare professionals.

TIRCON-reg aims to * continue the provision of a global registry and natural history study for NBIA disorders * harmonize and cover existing national and single site registries * enable participation of countries and single sites that so far have no access to an NBIA registry * join forces in order to recruit sufficient numbers of patients * define the natural history of NBIA disorders * define the most appropriate outcome measures * inform the design and facilitate the conduction of clinical trials

The main goal of the project is provision of a global registry for mitochondrial disorders to harmonize previous national registries, enable world-wide participation and facilitate natural history studies, definition of outcome measures and conduction of clinical trials.

To investigate potential differences in procedural outcomes of both commercially available transcatheter edge-to-edge mitral valve repair devices in a non-selected clinical setting.

Despite its common occurrence, still little is known about pathomechanisms determining different wheeze and asthma trajectories and phenotypes in children, and those beginning in adulthood. Therefore, deciphering underlying determinants for different childhood and adult asthma phenotypes is urgently needed to develop personalized treatment approaches targeting distinct underlying mechanisms. Thereby, secondary prevention early in the disease process can also be achieved. The decoding of such mechanisms and their translation to the individual patient is the aim of the Disease Area Asthma Allergy of the 'German Centre for Lung Research' (DZL).

Schizophrenia (SZ) is a broad clinical entity characterized by different subjective symptoms,behavioural signs, and disease course. Research has pointed to numerous biological indicators tentatively associated with neurocognitive dysfunction, brain structural and neurochemical alterations. Cognitive deficits occur as early as the prodromal phase of the illness and significantly determine its outcome. Pathophysiologically, SZ is regarded as a disconnectome disorder in which frontal and temporal brain regions are functionally disconnected, which contributes substantially to the development of cognitive dysfunction. Impaired connectivity is related to synaptic (microconnectivity) and myelin (macroconnectivity) plasticity. With design-based stereology, a decreased number of oligodendrocytes (OLs) in the CA4 hippocampal subregion as the basis for disturbed myelination and impaired cognition, but also a decrease in the prefrontal cortex were observed. Animal studies demonstrated that clemastine enhances remyelination by increasing the differentiation of oligodendrocyte precursor cells (OPCs) and showed that aerobic exercise increases the rate of remyelination and proliferation of OPCs; this clinically meaningful effect of aerobic exercise is stronger in combination with clemastine. Furthermore, aerobic exercise improves everyday functioning, measured by the Global Assessment of Functioning (GAF) scale, and cognitive dysfunction in SZ and increases hippocampal volume, especially the volume in the hippocampal CA4 subregion. This regional volume change correlates negatively with global and cell-specific polygenic risk scores (PRSs), indicating that OPCs are involved in the genetic risk mechanisms and disturbed plasticity underlying SZ. In patients with multiple sclerosis, 90 days' administration of clemastine fumarate 10.72 mg/day, corresponding to clemastine 8 mg/day, significantly decreased the P100 latency delay of visual evoked potentials (VEPs) as a sign of myelin repair. In a bicentric, randomized, double-blind, controlled phase IIb clinical trial with a 2-arm parallel group design in patients with SZ, the study will compare the effects of aerobic exercise training plus clemastine vs. aerobic exercise training plus placebo over a period of 3 months on 1) everyday functioning and 2) working memory as primary outcomes.

To investigate clinical and survival outcomes following transcatheter tricuspid valve repair or replacement.

Aerobic endurance training has shown positive effects on symptoms, cognition, daily functioning, and the structure of the hippocampus in patients with schizophrenia. The study investigates genetic and epigenetic influences on neuroplastic changes following three months of endurance training. A control group performs flexibility, strength, and balance training. The main objective is to examine the association between a genetic risk score for schizophrenia and volume increase in the CA4/DG region of the hippocampus. Additional goals include examining changes in synapses, brain structure, function, and metabolism, as well as clinical symptoms and cognitive performance.

This is the first randomized controlled trial comparing transesophageal echocardiography + fluoroscopy guided lead implantation vs. standard lead implantation guided by fluoroscopy only. Patients are randomized 1:1 in the two groups and followed up for up to 3 years.

TENDER is a multicenter, single-device, retrospective and prospective, observational study to assess safety and efficacy of the Tendyne Mitral Valve System in a real-world population.

Multicentre observational study of patients with severe tricuspid regurgitation and interventional treatment.