Aortic Valve DiseaseMIRACLENCT04717219
Myeloid Cells in Aortic Valve Stenosis
An observational study of Aortic Valve Disease and Aortic Valve Stenosis, run by Radboud University Medical Center at 3 sites in Netherlands.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Aortic Valve Disease, Aortic Valve Stenosis
- What is being tested?
- Blood drawing
- Type of treatment
- Injection or infusion
- How many people
- 400 participants
- Where
- 3 sitesNetherlands
- Study dates
- 19 Nov 2020to 31 Dec 2022
- Phase
- Observational
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
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.
Who may be able to join
- 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.
Who cannot join
- 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
Show all 9Show fewer
- 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
Trial locations and contacts
3 sites in 1 country.
Netherlands3 sites, 3 recruiting
- Not yet recruiting
Rijnstate
Arnhem
R. Pisters, MD, PhD
- Recruiting
Radboud university medical center
Nijmegen, 6500 GA
Niels Riksen, MD, PhD, 0031-24-3618819, niels.riksen@radboudumc.nl
- Not yet recruiting
Canisius Wilhelmina Ziekenhuis
Nijmegen
E.S. Zegers, MD
About this study
Official title: 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.
Read the 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.
- Conditions
- Aortic Valve Disease, Aortic Valve Stenosis
- Being tested
- Blood drawing
- Keywords
- calcific aortic valve disease, valvular heart disease, inflammation, innate immune cells
- Medical subject headings
- Aortic Valve Disease, Aortic Valve Stenosis, Heart Valve Diseases, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Blood drawingOther
Blood will be drawn after inclusion of the participants.
| Study group | Role | What they receive |
|---|---|---|
| Severe CAVD with atherosclerosis | Participants with severe CAVD and significant atherosclerosis Receives: Other: Blood drawing | |
| Severe CAVS without atherosclerosis | Participants with severe CAVD without significant atherosclerosis Receives: Other: Blood drawing | |
| Moderate CAVD with atherosclerosis | Participants with mild or moderate CAVD and significant atherosclerosis Receives: Other: Blood drawing | |
| Moderate CAVD without atherosclerosis | Participants with mild or moderate CAVD without significant atherosclerosis Receives: Other: Blood drawing | |
| 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). Receives: Other: Blood drawing | |
| 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. Receives: Other: Blood drawing |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jan 2021
- Study start19 Nov 2020
- Primary completion31 Dec 2022 (estimated)
- Study completion31 Dec 2022 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Aortic Valve DiseaseStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Case-control
- Time perspective
- Prospective
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Radboud University Medical Center
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Niels Riksen, Radboud University Medical Center
- Investigators
- Niels P. Riksen, prof. dr., Principal investigator, Radboud University Medical Center
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04717219
- Sponsor's protocol ID
- NL72973.091.20
- Acronym
- MIRACLE
- Status last verified
- Apr 2022
- First submitted
- 11 Jan 2021
- Last updated
- 12 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
van Broekhoven A, van Doorn EPM, Broeders W, Cetinyurek-Yavuz A, Zegers ES, Netea MG, Vonk ABA, van Royen N, Niessen HWM, Cornel JH, Riksen NP, El Messaoudi S. Exploratory Analysis of the Innate Immune System in Aortic Stenosis Patients With and Without ASCVD. JACC Basic Transl Sci. 2026 Oct 14;11(11):101692. doi: 10.1016/j.jacbts.2026.101692. Online ahead of print.
PubMed 42874162
Study at a glance
From the registry record, last updated by the sponsor on 12 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Myeloid Cell Reprogramming in Aortic Valve Stenosis
- ClinicalTrials.gov ID
- NCT04717219
- Acronym / sponsor ID
- MIRACLE / NL72973.091.20
- Conditions
- Aortic Valve Disease, Aortic Valve Stenosis
- Keywords
- calcific aortic valve disease, valvular heart disease, inflammation, innate immune cells
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- Radboud University Medical CenterUniversity, hospital or other
- Study start
- 19 Nov 2020 (actual)
- Primary completion
- 31 Dec 2022 (estimated)
- Study completion
- 31 Dec 2022 (estimated)
- First posted
- 22 Jan 2021 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Investigators plan to characterize systemic inflammation and circulating immune cells in participants with moderate and severe calcific aortic valve disease and matched healthy controls.
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
- Observational model
- Case-control
- Time perspective
- Prospective
- Number of arms
- 6
| Arm | Type | Receives |
|---|---|---|
| Severe CAVD with atherosclerosis | – | Other: Blood drawingParticipants with severe CAVD and significant atherosclerosis |
| Severe CAVS without atherosclerosis | – | Other: Blood drawingParticipants with severe CAVD without significant atherosclerosis |
| Moderate CAVD with atherosclerosis | – | Other: Blood drawingParticipants with mild or moderate CAVD and significant atherosclerosis |
| Moderate CAVD without atherosclerosis | – | Other: Blood drawingParticipants with mild or moderate CAVD without significant atherosclerosis |
| Healthy controls | – | Other: Blood drawingHealthy 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). |
| Controls with bicuspid aortic valve stenosis | – | Other: Blood drawingControls with bicuspid aortic valve stenosis, without a history of atherosclerotic cardiovascular events, current typical complaints of angina pectoris or intermittent claudication. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- 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.
Key inclusion criteria (2 listed)
- 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.
Key exclusion criteria (9 listed)
- 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.
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Blood drawingBlood will be drawn after inclusion of the participants. | Other | Controls with bicuspid aortic valve stenosis, Healthy controls, Moderate CAVD with atherosclerosis, Moderate CAVD without atherosclerosis, Severe CAVD with atherosclerosis, Severe CAVS without atherosclerosis |
Primary outcome
Inflammatory phenotype of circulating immune cells.
Time frame: 2 years
The inflammatory phenotype of circulating immune cells will be measured by determining the cytokine production capacity after stimulation with relevant stimuli.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 12 Apr 2022.
- Derived from this study: PubMed 42874162van Broekhoven A, van Doorn EPM, Broeders W, Cetinyurek-Yavuz A, Zegers ES, Netea MG, Vonk ABA, van Royen N, Niessen HWM, Cornel JH, Riksen NP, El Messaoudi S. Exploratory Analysis of the Innate Immune System in Aortic Stenosis Patients With and Without ASCVD. JACC Basic Transl Sci. 2026 Oct 14;11(11):101692. doi: 10.1016/j.jacbts.2026.101692. Online ahead of print.
- Individual participant dataSharing planned: Undecided
Related trials for Aortic Valve Disease
Active, not recruitingObservational study
REdo Transcatheter Aortic VALVE Implantation for the Management of Transcatheter Aortic Valve Failure
Aortic Valve Stenosis
Recruiting
ARTIST: Aortic Regurgitation Trial Investigating Surgery Versus Trilogy™
Aortic Regurgitation, Aortic Valve Insufficiency
Not yet recruiting
NHLBI SESAME (SEptal Scoring Along Midline Endocardium) Multi-Center Prospective Study Using Improvised Off-Label Devices
Hypertrophic Cardiomyopathy, Left Ventricular Outflow Obstruction
Not yet recruiting
Exercise and Diet Supplements for Older Patients Undergoing TAVI: the IRON-TAVI Trial
Aortic Stenosis Disease, Aortic Stenosis Symptomatic
Not yet recruiting
A Clinical Trial to Evaluate the Effects of the NeuEve Dryness Treatment Kit on Vaginal Health, Comfort, and Quality of Life in Postmenopausal Women
Relieves Vaginal Dryness / Improves Self-Lubrication, Improves Strength & Elasticity of Vagina (Aka Collagen and Elastin)
Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Niels P. Riksen, prof. dr. principal investigator
Radboud University Medical Center
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Aortic Valve Disease and Aortic Valve Stenosis, run by Radboud University Medical Center at 3 sites in Netherlands.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 9 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 12 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Netherlands. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Niels P. Riksen, prof. dr. (+31-343618819, Niels.Riksen@radboudumc.nl), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Inflammatory phenotype of circulating immune cells. (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04717219, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 12 Apr 2022.