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Aortic StenosisGut-CASNCT06021535

Involvement of the Gut Microbiota in Calcified Aortic Stenosis

An observational study of Aortic Stenosis and Gastrointestinal Microbiome, run by Insel Gruppe AG, University Hospital Bern.

Not yet recruiting

Opening soon. The study is approved but enrolment has not started yet. Sites may already take enquiries.

Sites and contacts
Official record
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Trial summary

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. Read more about this study

Who is it for?
Ages 18 to 90 years
How many people
100 participants
Where
No sites listed yet
Study dates
1 Jan 2024to 31 Dec 2028
Phase
Observational
Are there results?
Not yet: the study is under way

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 to 90 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Study 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.

Who may be able to join

  • Group of patients with CAS:
  • 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
  • Aortic sclerosis: calcified remodeling of the aortic valve visible on ultrasound or CT.
  • Control group - free of CAS:
  • No calcified aortic stenosis verified on a cardiac ultrasound or CT not older than 3 months

Who cannot join

  • 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 locations and contacts

No sites are listed yet. Contact the study team or a site near you to ask about taking part.

About this study

Official title: Involvement of the Gut Microbiota and Its Metabolites in the Pathophysiology of Calcified Aortic Stenosis

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.

Read more

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.

Being tested
No intervention
Medical subject headings
Aortic Valve Stenosis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • No interventionOther

    No intervention

Study groups in NCT06021535
Study groupRoleWhat they receive
Calcified Aortic StenosisPatients with calcified aortic valve or aortic stenosis will be enrolled Stool, blood samples and aortic valve of operated patients will be retrieved to evaluate the composition of the gut microbiota and its metabolites A follow up is planned for patients with no intervention on the aortic valve to assess the evolution of the aortic stenosis and the change in the gut microbiota.
Receives: Other: No intervention
ControlPatients without calcified aortic valve will be enrolled Stool and blood samples will be retrieved to evaluate the composition of the gut microbiota and its metabolites No follow up is scheduled.
Receives: Other: No intervention

What is being measured

The primary outcome is the main question the study is designed to answer.

  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.

    Measured: 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 (7)
  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).

    Measured: 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).

    Measured: 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.

    Measured: 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)

    Measured: 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)

  5. Diversity of bacteria families in men and women

    Primary endpoint: The primary endpoint is the evaluation (16S 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.

    Measured: 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)

  6. Prevalence of bacterial families or species in the microbiota of patients with CAS over the course of time and disease progression.

    Primary endpoint: The primary endpoint is the evaluation (16S 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.

    Measured: 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 each year of follow up (an average of 2 years)

  7. Prevalence of bacterial families or species in the microbiota of men versus women with CAS over the course of time and disease progression.

    Primary endpoint: The primary endpoint is the evaluation (16S 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.

    Measured: 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 each year of follow up (an average of 2 years)

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted1 Sep 2023
  2. Study start1 Jan 2024 (estimated)
  3. Primary completion31 Dec 2025 (estimated)
  4. Study completion31 Dec 2028 (estimated)

Resources

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
100 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT06021535
Sponsor's protocol ID
BASEC Nr (2023-01173)
Acronym
Gut-CAS
Status last verified
Aug 2023
First submitted
22 Aug 2023
Last updated
1 Sep 2023
Results posted
No
FDA-regulated drug
No
FDA-regulated device
No
Individual data sharing
No

Publications

  • Kocyigit D, Tokgozoglu L, Gurses KM, Stahlman M, Boren J, Soyal MFT, Canpinar H, Guc D, Saglam Ayhan A, Hazirolan T, Ozer N. Association of dietary and gut microbiota-related metabolites with calcific aortic stenosis. Acta Cardiol. 2021 Jul;76(5):544-552. doi: 10.1080/00015385.2020.1853968. Epub 2020 Dec 18.

    PubMed 33334254
  • Liu Z, Li J, Liu H, Tang Y, Zhan Q, Lai W, Ao L, Meng X, Ren H, Xu D, Zeng Q. The intestinal microbiota associated with cardiac valve calcification differs from that of coronary artery disease. Atherosclerosis. 2019 May;284:121-128. doi: 10.1016/j.atherosclerosis.2018.11.038. Epub 2018 Dec 4.

    PubMed 30897381
  • Agus A, Planchais J, Sokol H. Gut Microbiota Regulation of Tryptophan Metabolism in Health and Disease. Cell Host Microbe. 2018 Jun 13;23(6):716-724. doi: 10.1016/j.chom.2018.05.003.

    PubMed 29902437
  • Shan Y, Pellikka PA. Aortic stenosis in women. Heart. 2020 Jul;106(13):970-976. doi: 10.1136/heartjnl-2019-315407. Epub 2020 Mar 22.

    PubMed 32201373
  • Morvan M, Arangalage D, Franck G, Perez F, Cattan-Levy L, Codogno I, Jacob-Lenet MP, Deschildre C, Choqueux C, Even G, Michel JB, Back M, Messika-Zeitoun D, Nicoletti A, Caligiuri G, Laschet J. Relationship of Iron Deposition to Calcium Deposition in Human Aortic Valve Leaflets. J Am Coll Cardiol. 2019 Mar 12;73(9):1043-1054. doi: 10.1016/j.jacc.2018.12.042.

    PubMed 30846099
  • Yilmaz B, Fuhrer T, Morgenthaler D, Krupka N, Wang D, Spari D, Candinas D, Misselwitz B, Beldi G, Sauer U, Macpherson AJ. Plasticity of the adult human small intestinal stoma microbiota. Cell Host Microbe. 2022 Dec 14;30(12):1773-1787.e6. doi: 10.1016/j.chom.2022.10.002. Epub 2022 Oct 31.

    PubMed 36318918

Questions about this trial

What is this clinical trial studying?

An observational study of Aortic Stenosis and Gastrointestinal Microbiome, run by Insel Gruppe AG, University Hospital Bern.

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 8 inclusion and 4 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: opening soon, as of the sponsor's last update on 1 Sep 2023. Status can change between updates, so confirm with the study contact before making plans.

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?

This study is still under way. Results are not available in the source record yet.

How can a doctor refer a patient or contact the research team?

Contact Caroline Nguyen, MD (+41316325000, caroline.chong-nguyen@insel.ch), or a site near the patient. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Richness of the gut microbiota (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)). 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 NCT06021535, which also lists 6 linked publications.

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 1 Sep 2023.

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