Acute Coronary Syndrome
Conditions
Keywords
Atherosclerosis, Mediterranean diet, microbiota, immune system, metabolome, proteome
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.
Interventions
OTHERMicrobiota analysis
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.
A study of immunological cell populations, inmunogenetics and cytokines will be carried out from fresh blood samples using antibody panels and flow cytometry
OTHERProteome analysis
A study of host and microbiota proteome will be carried out from samples using mass spectrometry
OTHERMetabolome analysis
A study of host and microbiota metabolome will be carried out from samples using MS-based as well as NMR-based methods
OTHERClinical evaluation
Clinical evaluation including hemostasis and biochemical studies
OTHERDiet evaluation
Biochemical analysis and questionaries for diet adherence and exercise registration
OTHERMedDiet
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
Sponsors
Hospital General Universitario Gregorio Marañon
Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
University of Navarra
Institut National de la Santé Et de la Recherche Médicale, France
Tel Aviv University
Göteborg University
Consorcio Centro de Investigación Biomédica en Red (CIBER)
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
PREVENTION
Masking
SINGLE (Investigator)
Masking description
Non-intervention or MedDiet intensive intervention group assignment will be made through an automated system. Each patient will be assigned a patient identification number that should appear on all eCRF pages (electronic case report), source documents and laboratory data. All researchers involved in the measurement of data, analysis and allocation of results will be blind. The MedDiet intensive intervention will be blind to the evaluation of the endpoints (the research team in charge of the measurement, analysis and awarding of the results will be blind). The samples will be coded and anonymously analyzed by each research team
Intervention 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.
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Fibrous cap thickness change | 12 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
| Measure | Time frame | Description |
|---|---|---|
| Intestinal microbiota composition changes | 12 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 |
| Oral microbiota composition changes | 12 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 |
| Adaptive immune system status changes | 12 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 |
| Innate immune system status changes | 12 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 |
| Endothelial dysfunction | 12 months | Vascular endothelial function measured using a Doppler pressure guidewire |
| Faecal protein profiling changes | 12 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 |
| Urine metabolome profiling changes | 12 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 |
| Blood metabolome profiling changes | 12 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 |
| Faecal metabolome profiling changes | 12 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 |
| Blood protein profiling changes | 12 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 |
Countries
Spain
Outcome results
None listed