Clinical trial NCT03842319: Impact of MEditerranean Diet, Inflammation and Microbiome After an Acute Coronary Syndrome
Official title: Impact of MEditerranean Diet, Inflammation and Microbiome on Plaque Vulnerability and Microvascular Dysfunction After an Acute Coronary Syndrome. A Randomized, Controlled, Mechanistic Clinical Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Acute Coronary Syndrome
Keywords: Atherosclerosis
Mediterranean diet
microbiota
immune system
metabolome
proteome
Lead sponsor: Consorcio Centro de Investigación Biomédica en Red (CIBER)
Sponsor class: OTHER_GOV
Collaborators: name: Hospital General Universitario Gregorio Marañon
name: Fundación para el Fomento de la Investigación Sanitaria y Biomédica de la Comunitat Valenciana
name: University of Navarra
name: Institut National de la Santé Et de la Recherche Médicale, France
name: Tel Aviv University
name: Göteborg University
First posted: 2019-02-15
Enrollment: 100
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
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.
Primary purpose: PREVENTION

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.

Eligibility criteria: 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

Primary outcomes:
measure: Fibrous cap thickness change
timeFrame: 12 months
Secondary outcomes:
measure: Endothelial dysfunction
timeFrame: 12 months
measure: Intestinal microbiota composition changes
timeFrame: 12 months
measure: Oral microbiota composition changes
timeFrame: 12 months
measure: Adaptive immune system status changes
timeFrame: 12 months
measure: Innate immune system status changes
timeFrame: 12 months
measure: Blood protein profiling changes
timeFrame: 12 months
measure: Faecal protein profiling changes
timeFrame: 12 months
measure: Urine metabolome profiling changes
timeFrame: 12 months
measure: Blood metabolome profiling changes
timeFrame: 12 months
measure: Faecal metabolome profiling changes
timeFrame: 12 months
Other outcomes:
Locations:
city: Madrid
country: Spain
facility: Hospital General Universitario Gregorio Marañón
Study officials:
affiliation: CIBER, HGUGM
name: Francisco Fernández-Avilés, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: Fernandez AI, Bermejo J, Yotti R, Martinez-Gonzalez MA, Mira A, Gophna U, Karlsson R, Al-Daccak R, Martin-Demiguel I, Gutierrez-Ibanes E, Charron D, Fernandez-Aviles F; MEDIMACS research team. The impact of Mediterranean diet on coronary plaque vulnerability, microvascular function, inflammation and microbiome after an acute coronary syndrome: study protocol for the MEDIMACS randomized, controlled, mechanistic clinical trial. Trials. 2021 Nov 12;22(1):795. doi: 10.1186/s13063-021-05746-z.