MIRACLE: Myeloid Cells in Aortic Valve Stenosis

Sponsor

Radboud University Medical Center (Other)

Overall Status

Recruiting

CT.gov ID

NCT04717219

Collaborator

(none)

400

Enrollment

Locations

25.4

Anticipated Duration (Months)

133.3

Patients Per Site

5.3

Patients Per Site Per Month

Study Details

Study Description

Brief Summary

Investigators plan to characterize systemic inflammation and circulating immune cells in participants with moderate and severe calcific aortic valve disease and matched healthy controls.

Condition or Disease	Intervention/Treatment	Phase
Aortic Valve Disease Aortic Valve Stenosis	Other: Blood drawing

Detailed Description

Calcific aortic valve disease (CAVD) is the most common type of valvular heart disease in the Western world. Due to the aging of the population, the impact of this disorder is expected to further increase in the next decades. The underlying pathophysiology remains incompletely defined and there are currently no effective medical treatments capable of altering its course, identifying a major unmet need in this growing population of patients.

Based on the similarities between CAVD and atherosclerosis in pathophysiology and shared risk factors, it is now hypothesized that activation of the innate immune system contributes to the development of CAVD. Therefore, the investigators will perform an observational study to assess the role of activation of the innate immune system in CAVD.

Study Design

Study Type:

Observational

Anticipated Enrollment :

400 participants

Observational Model:

Case-Control

Time Perspective:

Prospective

Official Title:

Myeloid Cell Reprogramming in Aortic Valve Stenosis

Actual Study Start Date :

Nov 19, 2020

Anticipated Primary Completion Date :

Dec 31, 2022

Anticipated Study Completion Date :

Dec 31, 2022

Arms and Interventions

Arm	Intervention/Treatment
Severe CAVD with atherosclerosis Participants with severe CAVD and significant atherosclerosis	Other: Blood drawing Blood will be drawn after inclusion of the participants.
Severe CAVS without atherosclerosis Participants with severe CAVD without significant atherosclerosis	Other: Blood drawing Blood will be drawn after inclusion of the participants.
Moderate CAVD with atherosclerosis Participants with mild or moderate CAVD and significant atherosclerosis	Other: Blood drawing Blood will be drawn after inclusion of the participants.
Moderate CAVD without atherosclerosis Participants with mild or moderate CAVD without significant atherosclerosis	Other: Blood drawing Blood will be drawn after inclusion of the participants.
Healthy controls Healthy controls without CAVD and without a history of atherosclerotic cardiovascular events, current typical complaints of angina pectoris or intermittent claudication and overt heart failure (NYHA class III/IV).	Other: Blood drawing Blood will be drawn after inclusion of the participants.
Controls with bicuspid aortic valve stenosis Controls with bicuspid aortic valve stenosis, without a history of atherosclerotic cardiovascular events, current typical complaints of angina pectoris or intermittent claudication.	Other: Blood drawing Blood will be drawn after inclusion of the participants.

Outcome Measures

Primary Outcome Measures

Inflammatory phenotype of circulating immune cells. [2 years]
The inflammatory phenotype of circulating immune cells will be measured by determining the cytokine production capacity after stimulation with relevant stimuli.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Yes

Inclusion Criteria:

Age > 18 years
Mild, moderate or severe degenerative aortic valve stenosis as defined by transthoracic echocardiography according to the 2017 ESC/EACTS guidelines for the management of valvular heart disease.

Exclusion Criteria:

Active auto-inflammatory or auto-immune diseases
Anti-inflammatory drugs
Vaccination less than one month before inclusion
Bone marrow transplantation
Active malignancy, except for local basal cell carcinoma or local squamous cell skin carcinoma, that can be treated curatively by excision.
History of endocarditis of the aortic valve
History of radiation therapy aimed at the chest
Acute ischemic cardiac event less than three months before inclusion
Systemic inflammation less than one month before inclusion with fever and/or for which antibiotics have been prescribed, with the exception for the use of nitrofurantoin for a urinary tract infection without fever