Involvement of the Gut Microbiota in Calcified Aortic Stenosis
Trial statusNot yet recruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age18-90
SponsorInsel Gruppe AG, University Hospital Bern
About this trial
Calcific aortic stenosis (CAS) is a disease characterized by progressive calcification of the aortic valve, obstructing the passage of blood from the left ventricle into the general circulation. It is the most frequent cause of valve disease in the elderly. To date, no means of preventing the disease has been discovered, and the only treatment available is valve replacement during cardiac surgery, or percutaneous implantation of a valve prosthesis when the narrowing becomes severe and causes symptoms.
The intestinal flora or microbiota, the reservoir of all the microorganisms in the gut, is implicated in numerous diseases, particularly of the intestine. But to date, no study has established a link between CAS and microbiota. The intestinal microbiota acts through molecules produced by itself or the host and passing into the bloodstream. In the pathophysiology of CAS, the valve leaflets are breached and do not heal. These molecules can enter and have beneficial or deleterious effects, in particular promoting calcification of aortic valve cells.
Concrete objectives:
Improve understanding of calcific aortic stenosis in humans Study the composition of intestinal flora in patients with aortic stenosis and compare it with healthy subjects Study the molecules in the intestinal flora likely to be involved in the development of aortic stenosis in humans.
Eligibility criteria
This trial does not accept healthy volunteersQualifiers
Calcified aortic stenosis diagnosed on a cardiac ultrasound or CT not older than 3 months
Severe aortic stenosis: surgical indication based on symptoms and ultrasound data (high gradient aortic stenosis : Vmax> 4m/s, mean gradient > 40mmHg, area < 1cm², low flow low-gradient CAS: left ventricular ejection fraction (LVEF) < 40%, Vmax< 4m/s, mean gradient < 40mmHg, area < 1cm², paradoxical low-gradient CAS: LVEF > 55%, Vmax< 4m/s, mean gradient < 40mmHg, area < 1cm²)
Moderate CAS: 3m/s <Vmax< 4m/s, 20mmHg < mean gradient < 40mmHg
Mild CAS: 2,6m/s < Vmax < 2.9m/s, mean gradient < 20mmHg
Disqualifiers
Treatment interfering with the composition of the intestinal microbiota: local or systemic corticosteroids within the last 3 months, antibiotics within the last 3 months, antiretrovirals, bile acid chelators (questran and colesevelam), HIV-targeted antiretroviral therapies, selective serotonin reuptake inhibitor-type antidepressants
Clinical criteria: history of cholecystectomy, documented chronic liver disease in the patient, failure to fast on the day of the blood test, inflammatory bowel disease
Patients requiring emergency intervention (myocardial infarction, acute aortic or mitral insufficiency, cardiogenic shock).
AS of rheumatic origin, infective endocarditis.
Trial population
In this study the investigators aim at enrolling patients with calcified aortic stenosis as well as a control group (patients without calcified aortic stenosis) and aim for an even distribution between female and male participants.
Trial design
Design model
Case-control
Time perspective
Prospective
Treatments tested in this trial
No intervention
Other interventionNo intervention
Treatment groups
100 Participants
are divided into 2 treatment groupsGroup A: Calcified Aortic Stenosis1 intervention
Group B: Control1 intervention
Trial outcomes
Primary outcomes
1
Richness of the gut microbiota
The primary endpoint is the evaluation (16S ribosomal ribonucleic acid (rRNA) sequencing) of the species richness using alpha diversity parameters such as the Shannon and Simpson index and diversity between samples using beta diversity with Bray-Curtis dissimilarity approach. The investigators will then identify the bacteria with taxonomy analysis and statistical differences will be done using MaAsLin (Microbiome Multivariable Association with Linear Models) for patients with and without CAS.
Time frame
The sample will be collected at the time of inclusion (with a margin of two additional days depending on the patient's ability to pass stools). The analysis will be performed at the end of the sample collection (an average of 2 years)Secondary outcomes
1
Comparison of the levels of the tryptophane metabolites of the gut microbiota in the blood, feces and the aortic valve between patients with and without CAS
The metabolites being studied include tryptophan metabolites (kynurenine pathway, serotonin pathway).
Time frame
The full analysis will be performed at the end of the sample collection. One intermediate analysis is scheduled when half of the samples are collected (one year and two years)2
Comparison of the levels of the short chain fatty acids (SCFA) metabolites of the gut microbiota in the blood, feces and the aortic valve between patients with and without CAS
The metabolites being studied include SCFA (acetate, propionate and butyrate).
Time frame
The full analysis will be performed at the end of the sample collection. One intermediate analysis is scheduled when half of the samples are collected (one year and two years)3
Comparison of the levels of the trimethylamine N oxide (TMAO) metabolites of the gut microbiota in the blood, feces and the aortic valve between patients with and without CAS
TMAO is derived from trimethylamine (TMA), itself generated by the action of the gut microbiota on dietary choline and phosphatidylcholine contained in red meat, eggs, dairy products and saltwater fish. TMAO and its derivatives (L Carnitine) are measured in blood, stool and valves.
Time frame
The full analysis will be performed at the end of the sample collection. One intermediate analysis is scheduled when half of the samples are collected (one year and two years)4
Comparison of the levels of the bile acids metabolites of the gut microbiota in the blood, feces and the aortic valve between patients with and without CAS
The metabolites being studied include 4 bile acids and their derivatives (Cholic, Chenodeoxycholic, Deoxycholic and Lithocholic acid)
Time frame
The full analysis will be performed at the end of the sample collection. One intermediate analysis is scheduled when half of the samples are collected (one year and two years)Locations
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Source ClinicalTrials.gov
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