The Microbiome as a Target for Precision Medicine in Atherosclerosis

Acute Coronary Syndrome Clinical Trial

— MIGATER  

Official title:

Microbiome, Inflammation and Genetics as a Target for Precision Medicine in AThERosclerosis

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03434483
• Other study ID #: FIBHGM-MIGATER
• Secondary ID: PIE 16/00055
• Status: Completed
• Start date: February 25, 2018
• Est. completion date: February 8, 2021

Study information

• Verified date: August 2021
• Source: Hospital General Universitario Gregorio Marañon
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational [Patient Registry]

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 156
• Est. completion date: February 8, 2021
• Est. primary completion date: February 8, 2021
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria Acute coronary syndrome group:

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

Exclusion Criteria Acute coronary syndrome group:

• 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

Aditional Inclusion Criteria for angiographic substudy group:

• 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).

Aditional Exclusion Criteria for angiographic substudy group:

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

Inclusion Criteria Chronic atherosclerosis group:

• 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 Chronic atherosclerosis group:

• 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

Related Conditions & MeSH terms

• Acute Coronary Syndrome
• Atherosclerosis

Intervention

Procedure:
• 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.

Genetic:
• 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

Other:
• 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.
• Immunological analysis
A study of immunological cell populations and cytokines will be carried out from fresh blood samples using antibody panels and flow cytometry
• Clinical evaluation
Clinical evaluation including hemostasis and biochemical studies and questionaries for diet and exercice registration

Locations

Country	Name	City	State
Spain	Hospital General Universitario Gregorio Maranon	Madrid

Sponsors (2)

Lead Sponsor	Collaborator
Hospital General Universitario Gregorio Marañon	Fundación para la Investigación Biomédica del Hospital Gregorio Maranon

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change from baseline in clinical evaluation at 12 months	Cardiac events register including hemostasis and biochemical determinations	Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months
Primary	Change from baseline in fibrous cap thickness at 12 months	Angiographic substudy-Change from baseline in the thickness of the fibrous cap (µm) of an atherosclerotic plaque in the nonculprit vessel as measured using optical coherence tomography	Inclusion and 12 months
Secondary	Endothelial dysfunction	Angiographic substudy-Micro and macrovascular endothelial function measured using a Doppler pressure guidewire	Inclusion and 12 months
Secondary	Intestinal microbiota composition changes 16S	Changes from baseline in intestinal microbiota will be analysed using the 16S rRNA target gene sequencing approach at 1 week, 1 month, 3 months, 6 months and 12 months	Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months
Secondary	Intestinal microbiota composition changes metagenome	Changes from baseline in intestinal microbiota will be analysed using the metagenome sequencing approach at 1 week, 1 month, 3 months, 6 months and 12 months	Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months
Secondary	Blood microbiota composition changes 16S	Changes from baseline in blood microbiota will be analysed using the 16S rRNA target gene sequencing approach at 1 week, 1 month, 3 months, 6 months and 12 months	Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months
Secondary	Blood microbiota composition changes metagenome	Changes from baseline in blood microbiota will be analysed using the metagenome sequencing approach at 1 week, 1 month, 3 months, 6 months and 12 months	Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months
Secondary	Oral microbiota composition changes 16S	Changes from baseline in oral microbiota will be analysed using the 16S rRNA target gene sequencing approach at 1 week, 1 month, 3 months, 6 months and 12 months	Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months
Secondary	Oral microbiota composition changes metagenome	Changes from baseline in oral microbiota will be analysed using the genome sequencing approach at 1 week, 1 month, 3 months, 6 months and 12 months	Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months
Secondary	Adaptive immune system status changes	Changes from baseline of adaptive immune cell lineages will be assessed dynamically using high performance cytometry at 1 week, 1 month, 3 months, 6 months and 12 months	Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months
Secondary	Innate immune system status changes	Changes from baseline of innate immune cell lineages will be assessed dynamically using high performance cytometry at 1 week, 1 month, 3 months, 6 months and 12 months	Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months