Impact of MEditerranean Diet, Inflammation and Microbiome After an Acute Coronary Syndrome

Study Overview
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Brief Summary
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In the MEDIMACS project, the investigators will use a randomized clinical-trial design to address the effects of mediterranean diet on atherosclerotic plaque vulnerability and coronary endothelial function in order to decipher complex interplays between diet, microbiome, immunological and metabolic responses and coronary atherosclerosis. The investigators will focus on patients after an episode of acute coronary syndrome and use state-of-the-art techniques to address atherosclerotic plaque composition and coronary endothelial function. A number of different -omic approaches will be used to address effector pathways. The insights provided by this study will allow identifying potential new dietary, microbiota and/or metabolic targets for the treatment of atherosclerosis

Detailed Description
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Coronary atherosclerosis is a leading cause of mortality and disability worldwide. Continuous efforts are needed to improve secondary prevention and understand the mechanism underlying disease progression. Based on primary prevention trials, a potential benefit of the Mediterranean diet after an acute coronary syndrome can be anticipated. The integrated microbiome-mediated/ immunologic and metabolic pathways by which the Mediterranean diet modifies cardiovascular risk remain mostly unknown. Intestinal and oral dysbiosis is involved in the pathogenesis of atherosclerosis and microbiome dynamics may account for some of the observed benefits of Mediterranean diet. The first objective of the trial is to evaluate the effects of a well-controlled Mediterranean diet intervention on atherosclerotic plaque vulnerability and coronary endothelial dysfunction after an episode of acute coronary syndrome. The second objective is to decipher the interplays among diet, microbiota, immunity and metabolism responsible for the observed effects. The investigators propose a randomized mechanistic clinical trial, using state-of-the-art efficacy read-outs. The multidisciplinary consortium includes highly experienced cardiologists, nutritionists and experts in translational research in immunology, microbiomics, genomics, proteomics, metabolomics and metagenomics. This study will provide valuable insights to identify potential microbiome therapeutic targets for coronary artery disease.

Official Title
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Impact of MEditerranean Diet, Inflammation and Microbiome on Plaque Vulnerability and Microvascular Dysfunction After an Acute Coronary Syndrome. A Randomized, Controlled, Mechanistic Clinical Trial.

Conditions
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Acute Coronary Syndrome

Intervention / Treatment
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* Other: Microbiota analysis
* Other: Immunological analysis
* Other: Proteome analysis
* Other: Metabolome analysis
* Other: Clinical evaluation
* Other: Diet evaluation
* Other: MedDiet


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult patients undergoing cardiac catheterization for an acute coronary syndrome. At least 1 non-causal lesion in a coronary segment with a stenosis diameter between 40-70% that will not be submitted to intervention during the revascularization procedure. Disposition and possibility to modify the diet. With the ability to track and answer questionnaires. Signature of informed consent for the study Exclusion Criteria: TIMI score <3 in the injury Reference lesion with diameter <2.0 mm LV ejection fraction (EF) less than 45%. Active systemic infection Active periodontal disease Chronic inflammatory disease Active treatment with corticosteroids or immunomodulators Renal insufficiency with glomerular filtration less than 30 mL / min Severe hepatic insufficiency (liver cirrhosis in Child B or C stages). Comorbidity with life expectancy of less than one year

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Intervention Group: High intensity Mediterranean diet in secondary prevention after acute coronary syndrome. Control Group: recommendation of a standard of care, standard Mediterranean diet. Duration of the intervention per participant: 12 months. Follow-up period per participant: 12 months.
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Control<br>In patients allocated to the control group, the currently used Spanish Mediterranean diet will be recommended as part of a standard high-quality secondary prevention program, where the patient is invited to participate in a single 45 minute nutritional educational group session. Interventions: Microbiota analysis, Immunological analysis, Proteome analysis, Metabolome analysis, Clinical evaluation | Other: Microbiota analysis<br>* From the feces and oral cavity samples, 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.<br>Other: Immunological analysis<br>* A study of immunological cell populations, inmunogenetics and cytokines will be carried out from fresh blood samples using antibody panels and flow cytometry<br>Other: Proteome analysis<br>* A study of host and microbiota proteome will be carried out from samples using mass spectrometry<br>Other: Metabolome analysis<br>* A study of host and microbiota metabolome will be carried out from samples using MS-based as well as NMR-based methods<br>Other: Clinical evaluation<br>* Clinical evaluation including hemostasis and biochemical studies<br>Other: Diet evaluation<br>* Biochemical analysis and questionaries for diet adherence and exercise registration<br>|
| Experimental: High-intensity MedDiet<br>Patients allocated to the interventional group will be individually evaluated by a dietitian and will participate in dedicated individual and group sessions at baseline, and at 3, 6, 9 and 12 months. In the interventional group, a personalized MedDiet will assess chemical and nutritional composition and total energy intake will be adapted to participant's weight, age, and requirements, and the dietitian's tailored advice to his/her individual needs. A 14-item dietary screen for adherence to the Mediterranean diet will be used to personalize the intervention and negotiate dietary changes. Furthermore, free virgin olive oil, recipes, shopping list and designed weekly menus will be provided to maximize the differences between groups. Interventions: MedDiet, Microbiota analysis, Immunological analysis, Proteome analysis, Metabolome analysis, Clinical evaluation, Diet evaluation | Other: Microbiota analysis<br>* From the feces and oral cavity samples, 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.<br>Other: Immunological analysis<br>* A study of immunological cell populations, inmunogenetics and cytokines will be carried out from fresh blood samples using antibody panels and flow cytometry<br>Other: Proteome analysis<br>* A study of host and microbiota proteome will be carried out from samples using mass spectrometry<br>Other: Metabolome analysis<br>* A study of host and microbiota metabolome will be carried out from samples using MS-based as well as NMR-based methods<br>Other: Clinical evaluation<br>* Clinical evaluation including hemostasis and biochemical studies<br>Other: Diet evaluation<br>* Biochemical analysis and questionaries for diet adherence and exercise registration<br>Other: MedDiet<br>* The high-intensity Mediterranean diet will include the promotion of the following: a) abundant use of olive oil (>40 g/d) for cooking and dressing dishes; b) consumption of >2 daily servings of vegetables; c) >2-3 daily serving of fresh fruits; d) >3 weekly servings of legumes; e) >3 weekly servings of fish or seafood; f) >1 weekly serving of nuts or seeds; g) select white meats instead of red meats or processed meats; and h) cook regularly with tomato, garlic and onion adding or no other aromatic herbs, and dress vegetables, pasta, rice and other dishes with tomato, garlic and onion adding or no other aromatic herbs. Two main meals per day should be eaten (seated at a table, lasting more than 20 minutes). A recommendation to drink a glass of wine per day during meals is given. Limited consumption is advised for cured ham, red meat, chocolate, cured or fatty cheeses<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Fibrous cap thickness change | Change in the thickness of the fibrous layer of the atheroma plaque in the non-culprit vessel measured by optical coherence tomography at 12 months. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Endothelial dysfunction | Vascular endothelial function measured using a Doppler pressure guidewire | 12 months | 
| Intestinal microbiota composition changes | Changes from baseline in intestinal microbiota will be analysed using the 16S rRNA target gene sequencing approach at 3 months, 6 months, 9 months and 12 months | 12 months | 
| Oral microbiota composition changes | Changes from baseline in oral microbiota will be analysed using the 16S rRNA target gene sequencing approach at 3 months, 6 months, 9 months and 12 months | 12 months | 
| Adaptive immune system status changes | Changes from baseline of adaptive immune cell lineages will be assessed dynamically using high performance cytometry at 3 months, 6 months, 9 months and 12 months | 12 months | 
| Innate immune system status changes | Changes from baseline of innate immune cell lineages will be assessed dynamically using high performance cytometry at 3 months, 6 months, 9 months and 12 months | 12 months | 
| Blood protein profiling changes | Changes from baseline of host protein-profiles from collected plasma samples will be analyzed for detection of biomarkers at 3 months, 6 months, 9 months and 12 months | 12 months | 
| Faecal protein profiling changes | Changes from baseline of host protein-profiles from collected faces samples will be analyzed for detection of biomarkers at 3 months, 6 months, 9 months and 12 months | 12 months | 
| Urine metabolome profiling changes | Changes from baseline of host metabolome profiles in urine will be analyzed using mass-spectrometry-based at 3 months, 6 months, 9 months and 12 months | 12 months | 
| Blood metabolome profiling changes | Changes from baseline of host metabolome profiles in blood will be analyzed using mass-spectrometry-based at 3 months, 6 months, 9 months and 12 months | 12 months | 
| Faecal metabolome profiling changes | Changes from baseline of metabolome profiles in faecal samples will be analyzed using mass-spectrometry-based at 3 months, 6 months, 9 months and 12 months | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Atherosclerosis, Mediterranean diet, microbiota, immune system, metabolome, proteome