The Microbiome as a Target for Precision Medicine in Atherosclerosis
- Conditions
- Acute Coronary SyndromeAtherosclerosis
- Interventions
- Procedure: Assessment of the atherosclerotic plaque in a moderate lession.Genetic: Gene variants in atherosclerosisOther: Microbiota analysisOther: Immunological analysisOther: Clinical evaluation
- Registration Number
- NCT03434483
- Lead Sponsor
- Hospital General Universitario Gregorio Marañon
- Brief 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.
- Detailed 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 & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 156
Not provided
Not provided
Study & Design
- Study Type
- OBSERVATIONAL
- Study Design
- Not specified
- Arm && Interventions
Group Intervention Description ACS-Angiographic substudy Microbiota analysis 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 ACS-Angiographic substudy Assessment of the atherosclerotic plaque in a moderate lession. 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 ACS-Angiographic substudy Gene variants in atherosclerosis 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 Chronic coronary atherosclerosis Immunological analysis Patients with chronic atherosclerosis. Gene variants in atherosclerosis. Microbiota analysis. Immunological analysis. Acute Coronary Syndrome Clinical evaluation Patients with an episode of acute coronary syndrome. Clinical evaluation 1 year. Gene variants in atherosclerosis. Microbiota analysis. Immunological analysis. Chronic coronary atherosclerosis Microbiota analysis Patients with chronic atherosclerosis. Gene variants in atherosclerosis. Microbiota analysis. Immunological analysis. Acute Coronary Syndrome Gene variants in atherosclerosis Patients with an episode of acute coronary syndrome. Clinical evaluation 1 year. Gene variants in atherosclerosis. Microbiota analysis. Immunological analysis. Chronic coronary atherosclerosis Clinical evaluation Patients with chronic atherosclerosis. Gene variants in atherosclerosis. Microbiota analysis. Immunological analysis. Acute Coronary Syndrome Microbiota analysis Patients with an episode of acute coronary syndrome. Clinical evaluation 1 year. Gene variants in atherosclerosis. Microbiota analysis. Immunological analysis. Acute Coronary Syndrome Immunological analysis Patients with an episode of acute coronary syndrome. Clinical evaluation 1 year. Gene variants in atherosclerosis. Microbiota analysis. Immunological analysis. ACS-Angiographic substudy Clinical evaluation 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 ACS-Angiographic substudy Immunological analysis 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 Chronic coronary atherosclerosis Gene variants in atherosclerosis Patients with chronic atherosclerosis. Gene variants in atherosclerosis. Microbiota analysis. Immunological analysis.
- Primary Outcome Measures
Name Time Method Change from baseline in clinical evaluation at 12 months Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months Cardiac events register including hemostasis and biochemical determinations
Change from baseline in fibrous cap thickness at 12 months Inclusion and 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
- Secondary Outcome Measures
Name Time Method Oral microbiota composition changes 16S Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months 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
Endothelial dysfunction Inclusion and 12 months Angiographic substudy-Micro and macrovascular endothelial function measured using a Doppler pressure guidewire
Intestinal microbiota composition changes metagenome Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months 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
Blood microbiota composition changes metagenome Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months 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
Intestinal microbiota composition changes 16S Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months 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
Oral microbiota composition changes metagenome Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months 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
Adaptive immune system status changes Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months 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
Blood microbiota composition changes 16S Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months 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
Innate immune system status changes Inclusion, 1 week, 1 month, 3 months, 6 months and 12 months 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
Trial Locations
- Locations (1)
Hospital General Universitario Gregorio Maranon
🇪🇸Madrid, Spain