The Microbiome as a Target for Precision Medicine in Atherosclerosis

NCT ID: NCT03434483

Last Updated: 2021-08-05

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

COMPLETED

Total Enrollment

156 participants

Study Classification

OBSERVATIONAL

Study Start Date

2018-02-25

Study Completion Date

2021-02-08

Brief Summary

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Cardiovascular diseases are the main cause of death in industrialized countries. Among them, atherosclerosis has the highest prevalence and constitutes a common pathological pathway responsible for the majority of cases of chronic ischemic heart disease, acute myocardial infarction, heart failure and cerebrovascular disease. Classic studies have confirmed well-established etiopathogenic factors of atherosclerosis based on genetic and immunological components and environmental modifying agents such as diet and exercise. But in addition, recent experimental studies have shown that dysbiosis (alteration of the microbiota) may be an additional factor that participates in the onset and progression of atherosclerosis. The objective of this study is to identify the potential interactions between changes in the microbiota, changes in the immune status, the clinical evolution and the instability and progression of atherosclerosis.

Detailed Description

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The study will prospectively study two groups of patients : 1) patients with acute coronary syndrome and 2) age and sex matched patients with chronic stable documented atherosclerosis.

Immune cell populations and immune-related metabolites will be characterized, the genetic profile of the main known functional variants will be determined, and the oral, gastrointestinal, and blood microbiota will be compared in both groups in a transversal observational design.

In addition, 1-year clinical follow-up will be performed and correlation with the evolution of the microbiota and immune response in a longitudinal design will be conducted.

Besides, an angiographic substudy, for those patients included in the study but that require revascularization of culprit artery according to clinical indication, will be 1 year follow-up and functional assessment and intravascular imaging and the degree of remodelling of the atherosclerotic plaque will be correlated with the evolution of the microbiota and immune response in a longitudinal design.

Conditions

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Acute Coronary Syndrome Atherosclerosis

Study Design

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Observational Model Type

CASE_CONTROL

Study Time Perspective

PROSPECTIVE

Study Groups

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Acute Coronary Syndrome

Patients with an episode of acute coronary syndrome. Clinical evaluation 1 year. Gene variants in atherosclerosis. Microbiota analysis. Immunological analysis.

Gene variants in atherosclerosis

Intervention Type GENETIC

From the blood samples of the patients, the total DNA will be extracted and the main functional variants identified in the literature will be genotyped

Microbiota analysis

Intervention Type OTHER

From the samples of blood, feces, oral cavity and blood, the DNA of the microbiota will be extracted using specific extraction kits and the microbiome will be analyzed through the study of 16S ribosomal RNA amplicons.

Immunological analysis

Intervention Type OTHER

A study of immunological cell populations and cytokines will be carried out from fresh blood samples using antibody panels and flow cytometry

Clinical evaluation

Intervention Type OTHER

Clinical evaluation including hemostasis and biochemical studies and questionaries for diet and exercice registration

ACS-Angiographic substudy

Patients included in the Acute Coronary Syndrome group with clinical indication for revascularization.

Clinical evaluation. Assessment of the atherosclerotic plaque in a moderate lession at baseline and 1-year .

Gene variants in atherosclerosis. Microbiota analysis. Immunological analysis

Assessment of the atherosclerotic plaque in a moderate lession.

Intervention Type PROCEDURE

In patients who have been successfully revascularized the artery responsible for AMI and also present an intermediate lesion (40-80%) in another coronary territory, the clinical care protocol of the Cardiology Service stipulates the need for a physiological assessment with guidance of pressure (FFR).

The thickness of the fibrous cap shall be measured using optical coherence tomography.

In addition to the FFR measurement, a complete physiological assessment with a Doppler-pressure guide. This will allow the procedure to be performed without additional risk to the patient. The physiological study will include the analysis of endothelium-dependent vascular function and endothelium-independent vascular function.

Gene variants in atherosclerosis

Intervention Type GENETIC

From the blood samples of the patients, the total DNA will be extracted and the main functional variants identified in the literature will be genotyped

Microbiota analysis

Intervention Type OTHER

From the samples of blood, feces, oral cavity and blood, the DNA of the microbiota will be extracted using specific extraction kits and the microbiome will be analyzed through the study of 16S ribosomal RNA amplicons.

Immunological analysis

Intervention Type OTHER

A study of immunological cell populations and cytokines will be carried out from fresh blood samples using antibody panels and flow cytometry

Clinical evaluation

Intervention Type OTHER

Clinical evaluation including hemostasis and biochemical studies and questionaries for diet and exercice registration

Chronic coronary atherosclerosis

Patients with chronic atherosclerosis. Gene variants in atherosclerosis. Microbiota analysis. Immunological analysis.

Gene variants in atherosclerosis

Intervention Type GENETIC

From the blood samples of the patients, the total DNA will be extracted and the main functional variants identified in the literature will be genotyped

Microbiota analysis

Intervention Type OTHER

From the samples of blood, feces, oral cavity and blood, the DNA of the microbiota will be extracted using specific extraction kits and the microbiome will be analyzed through the study of 16S ribosomal RNA amplicons.

Immunological analysis

Intervention Type OTHER

A study of immunological cell populations and cytokines will be carried out from fresh blood samples using antibody panels and flow cytometry

Clinical evaluation

Intervention Type OTHER

Clinical evaluation including hemostasis and biochemical studies and questionaries for diet and exercice registration

Interventions

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Assessment of the atherosclerotic plaque in a moderate lession.

In patients who have been successfully revascularized the artery responsible for AMI and also present an intermediate lesion (40-80%) in another coronary territory, the clinical care protocol of the Cardiology Service stipulates the need for a physiological assessment with guidance of pressure (FFR).

The thickness of the fibrous cap shall be measured using optical coherence tomography.

In addition to the FFR measurement, a complete physiological assessment with a Doppler-pressure guide. This will allow the procedure to be performed without additional risk to the patient. The physiological study will include the analysis of endothelium-dependent vascular function and endothelium-independent vascular function.

Intervention Type PROCEDURE

Gene variants in atherosclerosis

From the blood samples of the patients, the total DNA will be extracted and the main functional variants identified in the literature will be genotyped

Intervention Type GENETIC

Microbiota analysis

From the samples of blood, feces, oral cavity and blood, the DNA of the microbiota will be extracted using specific extraction kits and the microbiome will be analyzed through the study of 16S ribosomal RNA amplicons.

Intervention Type OTHER

Immunological analysis

A study of immunological cell populations and cytokines will be carried out from fresh blood samples using antibody panels and flow cytometry

Intervention Type OTHER

Clinical evaluation

Clinical evaluation including hemostasis and biochemical studies and questionaries for diet and exercice registration

Intervention Type OTHER

Other Intervention Names

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Coronary blood collection

Eligibility Criteria

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Inclusion Criteria

* Diagnosis of acute coronary syndrome
* Signature of informed consent for the study (Annex I).


* Clinical indication of coronary angiography in the acute phase (in the first 72 hours after its hospital diagnosis).
* At least one non-causal coronary lesion in a coronary segment with reference diameter\> 2 mm, stenosis between 40-80%, and TIMI 3 flow in this vessel (angiographic criteria, only confirmed after performing coronary angiography)
* Signature of informed consent for the substudy (Annex II).


* Angiographic diagnosis, using catheterization or computed tomography of coronary atherosclerotic disease.
* Clinical situation of stable chronic ischemic heart disease.
* Signature of informed consent for the study (Annex III).

Exclusion Criteria

* Previous Ejection fraction of VI less than 30%.
* History of heart failure
* Systemic inflammatory diseases
* In treatment with corticosteroids or immunomodulators
* In treatment with antibiotics during the last month


* Renal insufficiency with creatinine clearance less than 30 ml / h
* Hepatic insufficiency: patients with cirrhosis in Child B or C stages will be excluded.


* Previous Ejection fraction of VI less than 30%.
* History of heart failure
* Systemic inflammatory diseases
* In treatment with corticosteroids or immunomodulators
* In treatment with antibiotics during the last month
Minimum Eligible Age

18 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

No

Sponsors

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Fundación para la Investigación Biomédica del Hospital Gregorio Maranon

OTHER

Sponsor Role collaborator

Hospital General Universitario Gregorio Marañon

OTHER

Sponsor Role lead

Responsible Party

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Javier Bermejo Thomas

MD PhD Cardiology Department HGUGM

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Francisco Fernández-Aviles, Prof, MD

Role: STUDY_DIRECTOR

Hospital General Universitario Gregorio Marañón

Locations

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Hospital General Universitario Gregorio Maranon

Madrid, , Spain

Site Status

Countries

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Spain

References

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I Fernandez-Avila A, Gutierrez-Ibanes E, Martin de Miguel I, Sanz-Ruiz R, Gabaldon A, Fernandez-Aviles F, Gomez-Lara J, Fernandez-Castillo M, Vazquez-Cuesta S, Martinez-Legazpi P, Lozano-Garcia N, Blazquez-Lopez E, Yotti R, Lopez-Cade I, Reigadas E, Munoz P, Elizaga J, Correa R, Bermejo J. One-year longitudinal changes of peripheral CD4+ T-lymphocyte counts, gut microbiome, and plaque vulnerability after an acute coronary syndrome. Int J Cardiol Heart Vasc. 2024 Jun 4;53:101438. doi: 10.1016/j.ijcha.2024.101438. eCollection 2024 Aug.

Reference Type DERIVED
PMID: 38912228 (View on PubMed)

Other Identifiers

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PIE 16/00055

Identifier Type: OTHER_GRANT

Identifier Source: secondary_id

FIBHGM-MIGATER

Identifier Type: -

Identifier Source: org_study_id

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