Myeloid Cells in Aortic Valve Stenosis (MIRACLE)

Myeloid Cell Reprogramming in Aortic Valve Stenosis

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

Study Overview

• Status: Recruiting
• Conditions: Aortic Valve Stenosis; Aortic Valve Disease
• Intervention / Treatment: 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 Type: Observational
• Enrollment (Anticipated): 400

Contacts and Locations

• Study Contact: Name: Niels P. Riksen, prof. dr.; Phone Number: +31-343618819; Email: Niels.Riksen@radboudumc.nl

Study Locations

• Netherlands
  • Arnhem, Netherlands
    • Not yet recruiting
    • Rijnstate
    • Contact: R. Pisters, MD, PhD
  • Nijmegen, Netherlands
    • Not yet recruiting
    • Canisius Wilhelmina Ziekenhuis
    • Contact: E.S. Zegers, MD
  • Nijmegen, Netherlands, 6500 GA
    • Recruiting
    • Radboud University Medical Center
    • Contact: Niels Riksen, MD, PhD; Phone Number: 0031-24-3618819; Email: niels.riksen@radboudumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Patients who present themselves or are already known at the department of cardiology or cardiothoracic surgery with the diagnosis of moderate or severe aortic valve stenosis as defined by transthoracic echocardiography according to the 2017 ESC/EACTS guidelines for the management of valvular heart disease.

Description

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

Study Plan

How is the study designed?

Number of groups / cohorts

6

Cohorts and Interventions

Group / Cohort	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.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Inflammatory phenotype of circulating immune cells.	The inflammatory phenotype of circulating immune cells will be measured by determining the cytokine production capacity after stimulation with relevant stimuli.	2 years

Collaborators and Investigators

• Sponsor: Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (ACTUAL): November 19, 2020
• Primary Completion (ANTICIPATED): December 31, 2022
• Study Completion (ANTICIPATED): December 31, 2022

Study Registration Dates

• First Submitted: January 11, 2021
• First Submitted That Met QC Criteria: January 19, 2021
• First Posted (ACTUAL): January 22, 2021

Study Record Updates

• Last Update Posted (ACTUAL): April 12, 2022
• Last Update Submitted That Met QC Criteria: April 4, 2022
• Last Verified: April 1, 2022

More Information

Terms related to this study

• Keywords: inflammation; calcific aortic valve disease; valvular heart disease; innate immune cells
• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Pathological Conditions, Anatomical; Heart Valve Diseases; Ventricular Outflow Obstruction; Aortic Valve Stenosis; Constriction, Pathologic; Aortic Valve Disease
• Other Study ID Numbers: NL72973.091.20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No