Cardiovascular Diseases
Conditions
Keywords
Statins, cardiovascular risk, primary prevention microbiota, metabolomics
Brief summary
Statins are effective in cardio-vascular prevention by lowering LDL-Cholesterol levels but also through other mechanisms poorly understood. Our hypothesis is that some of these effects are mediated by microbiota alteration, leading to diminution of expression of microbiota derived pro-atherogenic metabolites.
Detailed description
The aim of this prospective double blind placebo-controlled study is to evaluate the acute effects of statins on microbiota and its derived metabolites at 2 and 6 weeks.
Interventions
Patient participation for 6 weeks of treatment
DRUGPlacebo comparator
Patient participation for 6 weeks of treatment
Sponsors
Fondation Coeur et Recherche
ICAN Nutrition Education and Research
Fédération francaise de cardiologie
French Cardiology Society
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Masking description
Placebo manufactured as the treatment. Packaging identical.
Intervention model description
2 groups of patients having treatment or placebo
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Patient with cardiovascular risk requiring statins in primary prevention * Contraception for women of childbearing age
Exclusion criteria
* Previous antibiotics, proton pomp inhibitors, statins or other hypolipidemic drugs intake in the previous three months * Renal insufficiency with creatinine clearance \<40ml/min * Contra-indication to statins * Previously known conditions affecting muscles, or digestive system * Requirement of statins in secondary prevention
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Rate of trimethylamine N-oxide trimethylamine oxide in blood, measured post-prandially at week-6 in atorvastatin arm and placebo arm. | Week-6 | The main objective of the study is to measure the direct effect of Hydroxy-methyl-glutaryl-coenzyme A reductase inhibitors (Atorvastatin) on the production of atherogenic metabolites derived from intestinal microbiota |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of trimethylamine N-oxide trimethylamine oxide in blood, measured post-prandially at week-2 in atorvastatin arm and placebo arm. | week-2 | To evaluate the evolution of the whole circulating metabolomic profile linked to the introduction of statins |
| Rate of trimethylamine N-oxide trimethylamine oxide in blood, measured pre and post-prandially at week-2 and week-6 in atorvastatin arm. | Week-2 and week-6 | To evaluate changes in the microbiome related to the introduction of statins |
| Comparison between W0, W2 and W6 after initiation of atorvastatin vs placebo of circulating metabolomic profile (pre- and postprandial) | Week 2 and Week 6 | To correlate changes in lipid parameters induced by statins with metabolomic and lipidemic changes and microbiome. Rate of 100 metabolites will be analysed, and gathered as follows: metabolism of acylcarnitine (3), metabolism of bile acids (5), carbohydrate metabolism (1), dietary choline metabolism (3), metabolism of amino acids (34), vitamins and cofactors (7), metabolism of creatine (2), polyamine metabolism (3), purine metabolism (5), pyrimidine metabolism (9), tryptophan / kynurenine metabolism (21), caffeine metabolism (3), Citric Acid cycle (3), urea cycle (1) |
| Comparison between W0, W2 and W6 after initiation of atorvastatin vs placebo of the microbiome | Week 2 and Week 6 | To analyze the influence of the microbiota on the variability of response to atorvastatin. 169/5000 The stool will be analyzed by metagenomic sequencing using the shot gun technique, a direct sequencing that quantifies the number of bacterial genes and annotates them. |
Countries
France
Outcome results
None listed