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

Not Applicable
Completed
Conditions
Acute Coronary Syndrome
Interventions
Other: Microbiota analysis
Other: Immunological analysis
Other: Proteome analysis
Other: Metabolome analysis
Other: Clinical evaluation
Other: Diet evaluation
Other: MedDiet
Registration Number
NCT03842319
Lead Sponsor
Consorcio Centro de Investigación Biomédica en Red (CIBER)
Brief Summary

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

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.

Recruitment & Eligibility

Status
COMPLETED
Sex
All
Target Recruitment
100
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

Study & Design

Study Type
INTERVENTIONAL
Study Design
PARALLEL
Arm && Interventions
GroupInterventionDescription
ControlMicrobiota analysisIn 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
ControlProteome analysisIn 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
High-intensity MedDietMicrobiota analysisPatients 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
ControlDiet evaluationIn 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
ControlMetabolome analysisIn 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
High-intensity MedDietImmunological analysisPatients 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
High-intensity MedDietDiet evaluationPatients 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
ControlImmunological analysisIn 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
ControlClinical evaluationIn 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
High-intensity MedDietProteome analysisPatients 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
High-intensity MedDietClinical evaluationPatients 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
High-intensity MedDietMetabolome analysisPatients 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
High-intensity MedDietMedDietPatients 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
Primary Outcome Measures
NameTimeMethod
Fibrous cap thickness change12 months

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.

Secondary Outcome Measures
NameTimeMethod
Intestinal microbiota composition changes12 months

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

Adaptive immune system status changes12 months

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

Faecal metabolome profiling changes12 months

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

Innate immune system status changes12 months

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

Blood protein profiling changes12 months

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

Faecal protein profiling changes12 months

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

Blood metabolome profiling changes12 months

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

Endothelial dysfunction12 months

Vascular endothelial function measured using a Doppler pressure guidewire

Oral microbiota composition changes12 months

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

Urine metabolome profiling changes12 months

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

Trial Locations

Locations (1)

Hospital General Universitario Gregorio Marañón

🇪🇸

Madrid, Spain

Hospital General Universitario Gregorio Marañón
🇪🇸Madrid, Spain
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