Biomarkers and Mechanisms of Disease Progression and Outcome of Aortic Stenosis in Humans

NCT ID: NCT05851209

Last Updated: 2023-05-09

Basic Information

• Recruitment Status: NOT_YET_RECRUITING
• Total Enrollment: 938 participants
• Study Classification: OBSERVATIONAL
• Study Start Date: 2023-07-01
• Study Completion Date: 2031-07-31

Brief Summary

Biomarkers and mechanisms in the progression of aortic valve stenosis are sometimes not sufficiently understood. The current project will take into account image morphological and immunological aspects that predict the development of hemodynamically relevant aortic valve stenosis in order to identify high-risk patients and to develop further therapeutic options.

Detailed Description

Early recognition and management of aortic stenosis (AS) are substantial to avoid life threatening events during the clinical course. Multi-factorial complex mechanisms including fibrosis, oxidative stress, inflammation, angiogenesis, osteogenic differentiation and the effect of genetic risk variants have been proposed to be involved mechanistically in the pathogenesis of degenerative AS. It is crucial to identify the potentially involved mechanisms of AS progression in order to 1) identify patients at risk for pronounced cardiac damage and adverse outcomes that might benefit from early aortic valve replacement and 2) to discover treatment options that might slow down progression and lower adverse clinical events.

The consortium´s work has revealed that various inflammatory events play a substantial role for the onset and progression of aortic valve calcification and stenosis in cell culture and small animal experiments We hypothesize that patients with and without rapid progress to severe aortic stenosis differ in terms of genetic, immunological and imaging parameters early in the disease course, and that these parameters can be combined to create strong and reliable predictors of disease progression. Hence, we plan to assess multiple morphological, functional, genetic and immunological readouts and investigate their capacity to predict disease progression in AS in a clinical observational cohort of 938 patients with moderate AS.

This project is a working package as part of TRR259, which is a collaborative project between the three universities: Bonn, Cologne and Düsseldorf.

Conditions

Aortic Stenosis; Imaging; Pathogenesis; Disease Progression; Aortic Valve Calcification; Genetics

Study Design

• Observational Model Type: COHORT
• Study Time Perspective: PROSPECTIVE

Eligibility Criteria

Inclusion Criteria

• The patient has an acquired (tricuspid) moderate aortic valve stenosis, which is the reason for regular outpatient cardiological care.
• The subject has been informed verbally and in writing about the study and has given written consent to participate in this study.
• Age > 18 years

Exclusion Criteria

• The subject has contraindications for the performance of a magnetic resonance imaging or computed tomography (e.g., severe arrhythmias , contrast agent intolerance, a pacemaker, or severe renal insufficiency or severe renal insufficiency or claustrophobia).
• Presence of only mild or already high-grade acquired tricuspid Aortic valve stenosis
• Patient with bicuspid aortic valve
• Inability to follow the instructions of study personnel
• Lack of written informed consent

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

German Research Foundation

OTHER

Sponsor Role: collaborator

University Bonn

UNKNOWN

Sponsor Role: collaborator

University Cologne

UNKNOWN

Sponsor Role: collaborator

Collaborative Research Center

UNKNOWN

Sponsor Role: collaborator

Heinrich-Heine University, Duesseldorf

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Malte Kelm, Prof.

Role: STUDY_CHAIR

Clinic for Cardiology, Pneumology and Angiology at University Hospital Düsseldorf

Georg Nickenig, Prof.

Role: STUDY_CHAIR

University Bonn

Stephan Baldus, Prof.

Role: STUDY_CHAIR

University Cologne

Locations

University-Hospital Bonn

Bonn, , Germany

University Hospital Cologne

Cologne, , Germany

University-Hospital Düsseldorf Division of Cardiology, Pulmonary Disease and Vascular Medicine

Düsseldorf, , Germany

Countries

Germany

Central Contacts

Verena Veulemans, MD

Role: CONTACT

verena.veulemans@med.uni-duesseldorf.de

+4921118800

Lisa Dannenberg, MD

Role: CONTACT

lisa.dannenberg@med.uni-duesseldorf.de

+49211811800

Facility Contacts

Bernando S Franklin, Prof.

Role: primary

ranklin@uni-bonn.de

Julian Luetkens, MD

Role: backup

julian.luetkens@ukbonn.de

Victor Mauri, MD

Role: primary

victor.mauri@uk-koeln.de

Verena Veulemans, MD

Role: primary

verena.veulemans@med.uni-duesseldorf.de

+4921118800

Clinical Trial Unit

Role: backup

ctu@med.uni-duesseldorf.de

+49211811800

Related Links

https://www.trr259.uni-bonn.de/en/about-us

Website of TRR259

Other Identifiers

TRR259 C06

Identifier Type: -

Identifier Source: org_study_id