Cardiovascular DiseasesPhase 3METASTATINENCT03837925
Pharmaco-metabolomic Effects of Statins: METASTATINE
A Phase 3 study testing Atorvastatin 40mg Tablet in people with Cardiovascular Diseases, run by French Cardiology Society at 2 sites in France.
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. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Cardiovascular Diseases
- What is being tested?
- Atorvastatin 40mg Tablet
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 120 participants
- Where
- 2 sitesFrance
- Study dates
- 13 Jun 2019to 21 Dec 2022
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patient with cardiovascular risk requiring statins in primary prevention
- Contraception for women of childbearing age
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
About this study
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.
Read the 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.
- Conditions
- Cardiovascular Diseases
- Being tested
- Atorvastatin 40mg Tablet, Placebo comparator
- Keywords
- Statins, cardiovascular risk, primary prevention microbiota, metabolomics
- Medical subject headings
- Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Atorvastatin 40mg TabletDrug
Also called No other name
Patient participation for 6 weeks of treatment
Placebo comparatorDrug
Also called No other name
Patient participation for 6 weeks of treatment
| Study group | Role | What they receive |
|---|---|---|
| ATORVASTATIN | Experimental | 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 Receives: Drug: Atorvastatin 40mg Tablet |
| PLACEBO | Placebo comparator | 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 Receives: Drug: Placebo comparator |
What is being measured
The primary outcome is the main question the study is designed to answer.
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
Measured: Week-6
Secondary outcomes (4)
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
Measured: week-2
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
Measured: Week-2 and week-6
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)
Measured: Week 2 and Week 6
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.
Measured: Week 2 and Week 6
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Feb 2019
- Study start13 Jun 2019
- Primary completion21 Dec 2022
- Study completion21 Dec 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Cardiovascular DiseasesStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- 2 groups of patients having treatment or placebo
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 120 participants (actual)
Sponsor and investigators
- Lead sponsor
- French Cardiology Society
- Sponsor type
- University, hospital or other
- Collaborators
- Fondation Coeur et Recherche, ICAN Nutrition Education and Research, Fédération Française de Cardiologie
- Responsible party
- Sponsor
- Investigators
- Joe Elie SALEM, MD, Principal investigator, CIC 1421 CHU Pitie Salpetriere
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03837925
- Sponsor's protocol ID
- 2016-02
- Acronym
- METASTATINE
- Status last verified
- Jan 2023
- First submitted
- 7 Feb 2019
- Last updated
- 18 Jan 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 18 Jan 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmaco-metabolomic Effects of Statins: METASTATINE
- ClinicalTrials.gov ID
- NCT03837925
- Acronym / sponsor ID
- METASTATINE / 2016-02
- Conditions
- Cardiovascular Diseases
- Keywords
- Statins, cardiovascular risk, primary prevention microbiota, metabolomics
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 120 participants (actual)
- Lead sponsor
- French Cardiology SocietyUniversity, hospital or other
- Collaborators
- Fondation Coeur et Recherche, ICAN Nutrition Education and Research, Fédération Française de Cardiologie
- Study start
- 13 Jun 2019 (actual)
- Primary completion
- 21 Dec 2022 (actual)
- Study completion
- 21 Dec 2022 (actual)
- First posted
- 12 Feb 2019 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
- Model description
- 2 groups of patients having treatment or placebo
| Arm | Type | Receives |
|---|---|---|
| ATORVASTATIN | Experimental | Drug: Atorvastatin 40mg TabletAtorvastatin 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 |
| PLACEBO | Placebo comparator | Drug: Placebo comparatorPlacebo 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 |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Patient with cardiovascular risk requiring statins in primary prevention
- Contraception for women of childbearing age
Key exclusion criteria (5 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Atorvastatin 40mg TabletAlso: No other namePatient participation for 6 weeks of treatment | Drug | ATORVASTATIN |
| Placebo comparatorAlso: No other namePatient participation for 6 weeks of treatment | Drug | PLACEBO |
Primary outcome
Rate of trimethylamine N-oxide trimethylamine oxide in blood, measured post-prandially at week-6 in atorvastatin arm and placebo arm.
Time frame: 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
4 secondary outcomes
Rate of trimethylamine N-oxide trimethylamine oxide in blood, measured post-prandially at week-2 in atorvastatin arm and placebo arm.
Time frame: week-2
Rate of trimethylamine N-oxide trimethylamine oxide in blood, measured pre and post-prandially at week-2 and week-6 in atorvastatin arm.
Time frame: Week-2 and week-6
Comparison between W0, W2 and W6 after initiation of atorvastatin vs placebo of circulating metabolomic profile (pre- and postprandial)
Time frame: Week 2 and Week 6
Comparison between W0, W2 and W6 after initiation of atorvastatin vs placebo of the microbiome
Time frame: Week 2 and Week 6
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 18 Jan 2023.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Joe Elie SALEM, MD principal investigator
CIC 1421 CHU Pitie Salpetriere
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Atorvastatin 40mg Tablet in people with Cardiovascular Diseases, run by French Cardiology Society at 2 sites in France.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 5 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 18 Jan 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Rate of trimethylamine N-oxide trimethylamine oxide in blood, measured post-prandially at week-6 in atorvastatin arm and placebo arm. (time frame: Week-6). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 18 Jan 2023.