Pharmaco-metabolomic Effects of Statins: METASTATINE

Sponsor

French Cardiology Society (Other)

Overall Status

Recruiting

CT.gov ID

NCT03837925

Collaborator

Fondation Coeur et Recherche (Other), ICAN Nutrition Education and Research (Industry), Fédération francaise de cardiologie (Other)

130

Enrollment

Locations

Arms

45.6

Anticipated Duration (Months)

Patients Per Site

1.4

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Cardiovascular Diseases	Drug: Atorvastatin 40mg Tablet Drug: Placebo comparator	Phase 3

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

130 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

2 groups of patients having treatment or placebo2 groups of patients having treatment or placebo

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

Placebo manufactured as the treatment. Packaging identical.

Primary Purpose:

Treatment

Official Title:

Pharmaco-metabolomic Effects of Statins: METASTATINE

Actual Study Start Date :

Jun 13, 2019

Anticipated Primary Completion Date :

Mar 31, 2023

Anticipated Study Completion Date :

Mar 31, 2023

Arms and Interventions

Arm	Intervention/Treatment
Experimental: ATORVASTATIN Atorvastatin 40mg caps: one daily. 3 patient visits: inclusion / week 2 / week 6. At each visit, blood sampling, stool sampling, ECG, to evaluate the pharmaco-metabolomic effects of the Statine	Drug: Atorvastatin 40mg Tablet Patient participation for 6 weeks of treatment Other Names: No other name
Placebo Comparator: PLACEBO Placebo caps: one daily. 3 patient visits: inclusion / week 2 / week 6. At each visit, blood sampling, stool sampling, ECG to compare the pharmaco-metabolomic effects of the Statine between atorvastatin arm and placebo arm	Drug: Placebo comparator Patient participation for 6 weeks of treatment Other Names: No other name

Arm

Intervention/Treatment

Experimental: ATORVASTATIN

Atorvastatin 40mg caps: one daily. 3 patient visits: inclusion / week 2 / week 6. At each visit, blood sampling, stool sampling, ECG, to evaluate the pharmaco-metabolomic effects of the Statine

Drug: Atorvastatin 40mg Tablet

Patient participation for 6 weeks of treatment

Other Names:

No other name

Placebo Comparator: PLACEBO

Placebo caps: one daily. 3 patient visits: inclusion / week 2 / week 6. At each visit, blood sampling, stool sampling, ECG to compare the pharmaco-metabolomic effects of the Statine between atorvastatin arm and placebo arm

Drug: Placebo comparator

Patient participation for 6 weeks of treatment

Other Names:

No other name

Outcome Measures

Primary Outcome Measures

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 Outcome Measures

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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 75 Years

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

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