Pharmaco-metabolomic Effects of Statins: METASTATINE

Cardiovascular Diseases Clinical Trial

— METASTATINE  

Official title:

Pharmaco-metabolomic Effects of Statins: METASTATINE

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT03837925
• Other study ID #: 2016-02
• Status: Completed
• Phase: Phase 3
• Start date: June 13, 2019
• Est. completion date: December 21, 2022

Study information

• Verified date: January 2023
• Source: French Cardiology Society
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 120
• Est. completion date: December 21, 2022
• Est. primary completion date: December 21, 2022
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• Cardiovascular Diseases

Intervention

Drug:
• Atorvastatin 40mg Tablet
Patient participation for 6 weeks of treatment
• Placebo comparator
Patient participation for 6 weeks of treatment

Locations

Country	Name	City	State
France	CIC HEGP	Paris
France	CIC La Sapétrière	Paris

Sponsors (4)

Lead Sponsor	Collaborator
French Cardiology Society	Fédération francaise de cardiologie, Fondation Coeur et Recherche, ICAN Nutrition Education and Research

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Rate of trimethylamine N-oxide trimethylamine oxide in blood, measured post-prandially at week-6 in atorvastatin arm and placebo arm.	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	Week-6
Secondary	Rate of trimethylamine N-oxide trimethylamine oxide in blood, measured post-prandially at week-2 in atorvastatin arm and placebo arm.	To evaluate the evolution of the whole circulating metabolomic profile linked to the introduction of statins	week-2
Secondary	Rate of trimethylamine N-oxide trimethylamine oxide in blood, measured pre and post-prandially at week-2 and week-6 in atorvastatin arm.	To evaluate changes in the microbiome related to the introduction of statins	Week-2 and week-6
Secondary	Comparison between W0, W2 and W6 after initiation of atorvastatin vs placebo of circulating metabolomic profile (pre- and postprandial)	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)	Week 2 and Week 6
Secondary	Comparison between W0, W2 and W6 after initiation of atorvastatin vs placebo of the microbiome	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.	Week 2 and Week 6