AtorvastatinSTATIMPROVENCT03596684
Citrulline Efficacy to Improve Carbohydrate Metabolism Abnormalities in the Patient Treated With High Doses of Statin
A study testing citrulline supplementation and glucose tolerance test in people with Atorvastatin, run by Hospices Civils de Lyon at 1 site in France.
Trial summary
Hypercholesterolemia is a major cardiovascular risk factor. Statins are the first-line drug treatment for hypercholesterolemia and have been shown to be effective in both primary and secondary prevention of cardiovascular disease. Read more about this study
- Who is it for?
- Ages 40 to 75 years
- Conditions the study is for
- Atorvastatin
- What is being tested?
- citrulline supplementation and glucose tolerance test
- Type of treatment
- Pill or oral medicine, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 2 participants
- Where
- 1 siteFrance
- Study dates
- 26 Feb 2020to 7 Jun 2022
- Phase
- Interventional
- 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 40 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 40 years old < Age <75 years old
- men and women who are menopausal or who benefit from effective contraception
- treatment with atorvastatin at 40 or 80 mg / d for more than 3 months for primary prevention or secondary prevention at more than 3 months of the acute event (stroke, acute coronary syndrome) with or without ezetimibe (Ezetrol® monotherapy or in the form of associated with atorvastatin Liptruzet® 10/40 or 10/80)
- with a Body Mass Index (BMI) ≥28 kg / m2 and at least one other risk factor for statin-dependent diabetes among the following 4:
- Blood pressure ≥ 140/90 mmHg or hypotensive treatment
- Triglyceridemia ≥ 150 mg / l
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- Fasting blood glucose ≥ 100 mg / dl
- HDL-cholesterol <40 mg / dL in men, <50 mg / dL in women
- affiliated to a social security scheme
- signed informed consent
Who cannot join
- General criteria:
- Subject with unstable medical or psychological conditions that, in the opinion of the investigator, could lead the subject to be non-compliant or uncooperative during the study or could compromise the safety or participation of the subject under study L.1121-6, L.1121-8, L.1121-9 and L1122-1-2 of the Public Health Code).
- Major subjects under guardianship or deprived of their liberty by judicial or administrative decision.
- Plan for weight loss during the previous 3 months, current or future
- Dietary supplements for weight loss (based on plant extracts, algae, pre- and probiotics) in the previous 3 months or in progress
- Biological criteria:
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- Aspartate Amino Transferase (ASAT), Alanine Amino Transferase (ALAT)> 2 times the normal values
- HbA1c> 6.5%
- Creatin Phospho Kinase (CPK)> 2 times normal
- Triglycerid > 5g / L
- Renal insufficiency (clearance <60 mL / min)
- Demonstration of a biological abnormality deemed by the investigator to be clinically significant
- Medical and therapeutic criteria:
- Diabetes type 1 or 2
- Subjects treated with a drug that may interfere with the metabolism of citrulline and glucose (vitamin K antagonists, corticosteroids for more than 8 days before the study, anorexigenic drugs (Anorex, Fenproporex Deglaude AP, Moderatan, Prefamone Chronules), drugs (Orlistat, Lioresal)
- Any associated or uncontrolled progressive pathology (cardiac pathology, myocardial infarction of less than 6 months, arterial hypertension, psychiatric, renal or hepatic, cancer).
- pregnant or lactating woman
- Consumption of more than 3 glasses of alcohol per day.
- Subjects who express any reluctance to consume a food supplement morning and evening.
- eating disorders.
- Weight variation of +/- 5% during the previous 3 months
- Severe, progressive affection.
- Depressive or psychiatric state (antidepressant or psychotropic treatment).
- Medical or surgical history deemed by the investigator to be incompatible with this study.
- Blood donation in the 2 months prior to inclusion.
Trial locations and contacts
1 site in 1 country.
France1 site
Endocrinology and diabetology service, Louis Pradel Hospital
Bron, 69500
About this study
Hypercholesterolemia is a major cardiovascular risk factor. Statins are the first-line drug treatment for hypercholesterolemia and have been shown to be effective in both primary and secondary prevention of cardiovascular disease. However, long-term statin therapy is associated with impaired carbohydrate metabolism and increased risk of developing type 2 diabetes (T2D), particularly in patients with metabolic syndrome. The risk of developing T2D is higher with high doses of statins.
Currently the benefits of statins on the reduction of major cardiovascular events and mortality are considered superior to the risk of statin-induced diabetes T2D, and no change in clinical practice has been recommended to date. However, it now appears necessary to develop strategies to reduce the adverse effects of statins on carbohydrate metabolism and maintain the carbohydrate tolerance of patients on statins, especially in those at risk of developing T2D under statins.
Read more
Statins are able to induce the expression and activity of an enzyme synthesizing nitric oxide (NO), the endothelial NO synthase (eNOS), which helps improving insulin sensitivity and insulin secretion. However, availability and metabolism of its substrate arginine is impaired in obesity and T2D. The investigators thus hypothesized that providing citrulline to statin treated patients, the arginine precursor with better gastrointestinal tolerance and bioavailability than arginine, would beneficially impact their glucose homeostasis.
Tested in vivo by Béatrice Morio, a member of the CarMeN laboratory, combining citrulline to atorvastatin improved glucose tolerance and insulin sensitivity in mice fed a high fat-high sucrose diet. These data therefore suggest that combining citrulline to atorvastatin may improve glucose tolerance in statin-treated patients at high risk of developing T2D.
The objective of the study is therefore to investigate the impact of citrulline supplementation (5g/d) vs. placebo for 4 weeks on glucose tolerance assessed during an oral glucose tolerance test in patients at risk for developing T2D and treated with atorvastatin (40 or 80 mg / day).
- Conditions
- Atorvastatin
- Being tested
- citrulline supplementation, placebo supplementation, glucose tolerance test
- Keywords
- Carbohydrate Metabolism, Citrulline, Statine
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
citrulline supplementationDietary supplement
2.5 g per os of citrulline on the morning and the evening (5 g/ jour) during 4 weeks.
placebo supplementationDietary supplement
2.5 g of the product in the morning and in the evening during 4 weeks.
glucose tolerance testProcedure or surgery
2 exploration mornings distant from 28 days (before and after citrulline) will allow carrying out an oral glucose tolerance test of 2 hours (75 g glucose per os)
| Study group | Role | What they receive |
|---|---|---|
| citrulline | Experimental | citrulline 5g/d Receives: Dietary Supplement: citrulline supplementation; Procedure: glucose tolerance test |
| Placebo | Placebo comparator | pure mixture of amino acids: alanine, aspartate, glycine, proline, serine, histidine Receives: Dietary Supplement: placebo supplementation; Procedure: glucose tolerance test |
What is being measured
The primary outcome is the main question the study is designed to answer.
difference in the area under the curve of the glycemic response during a 75 g glucose tolerance test between the end and the beginning of citrulline supplementation versus placebo
Measured: 4 weeks
Secondary outcomes (3)
Difference in the index of insulin sensitivity determined during Oral Glucose Tolerance Test (OGTT) performed at the end and before the supplementation in citrulline versus placebo
Measured: 4 weeks
Difference in the index of insulin secretion determined during OGTT performed at the end and before the supplementation in citrulline versus placebo
Measured: 4 weeks
occurrence of adverse events and serious adverse events for assessment of tolerability
Measured: assessed up 8 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Jul 2018
- Study start26 Feb 2020
- Primary completion7 Jun 2022
- Study completion7 Jun 2022
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for AtorvastatinStudies of the same condition, open and under way.
- More trials run by Hospices Civils de LyonThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 2 participants (actual)
Sponsor and investigators
- Lead sponsor
- Hospices Civils de Lyon
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sybil Charriere, MD, Principal investigator, Hospices Civils de Lyon Endocrinology and diabetology service, Louis Pradel Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03596684
- Sponsor's protocol ID
- 69HCL17_0754
- Other IDs
- 2018-A00575-50
- Acronym
- STATIMPROVE
- Status last verified
- Apr 2023
- First submitted
- 4 Jun 2018
- Last updated
- 10 Apr 2023
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Apr 2023. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Citrulline Efficacy to Improve Carbohydrate Metabolism Abnormalities in the Patient Treated With High Doses of Statin
- ClinicalTrials.gov ID
- NCT03596684
- Acronym / sponsor ID
- STATIMPROVE / 69HCL17_0754
- Conditions
- Atorvastatin
- Keywords
- Carbohydrate Metabolism, Citrulline, Statine
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 2 participants (actual)
- Lead sponsor
- Hospices Civils de LyonUniversity, hospital or other
- Study start
- 26 Feb 2020 (actual)
- Primary completion
- 7 Jun 2022 (actual)
- Study completion
- 7 Jun 2022 (actual)
- First posted
- 24 Jul 2018 (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.
Hypercholesterolemia is a major cardiovascular risk factor. Statins are the first-line drug treatment for hypercholesterolemia and have been shown to be effective in both primary and secondary prevention of cardiovascular disease. However, long-term statin therapy is associated with impaired carbohydrate metabolism and increased risk of developing type 2 diabetes (T2D), particularly in patients with metabolic syndrome. The risk of developing T2D is higher with high doses of statins.
Currently the benefits of statins on the reduction of major cardiovascular events and mortality are considered superior to the risk of statin-induced diabetes T2D, and no change in clinical practice has been recommended to date. However, it now appears necessary to develop strategies to reduce the adverse effects of statins on carbohydrate metabolism and maintain the carbohydrate tolerance of patients on statins, especially in those at risk of developing T2D under statins.
Statins are able to induce the expression and activity of an enzyme synthesizing nitric oxide (NO), the endothelial NO synthase (eNOS), which helps improving insulin sensitivity and insulin secretion. However, availability and metabolism of its substrate arginine is impaired in obesity and T2D. The investigators thus hypothesized that providing citrulline to statin treated patients, the arginine precursor with better gastrointestinal tolerance and bioavailability than arginine, would beneficially impact their glucose homeostasis.
Tested in vivo by Béatrice Morio, a member of the CarMeN laboratory, combining citrulline to atorvastatin improved glucose tolerance and insulin sensitivity in mice fed a high fat-high sucrose diet. These data therefore suggest that combining citrulline to atorvastatin may improve glucose tolerance in statin-treated patients at high risk of developing T2D.
The objective of the study is therefore to investigate the impact of citrulline supplementation (5g/d) vs. placebo for 4 weeks on glucose tolerance assessed during an oral glucose tolerance test in patients at risk for developing T2D and treated with atorvastatin (40 or 80 mg / day).
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| citrulline | Experimental | Dietary Supplement: citrulline supplementation, Procedure: glucose tolerance testcitrulline 5g/d |
| Placebo | Placebo comparator | Dietary Supplement: placebo supplementation, Procedure: glucose tolerance testpure mixture of amino acids: alanine, aspartate, glycine, proline, serine, histidine |
Who may qualify
- Ages
- 40 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (10 listed)
- 40 years old < Age <75 years old
- men and women who are menopausal or who benefit from effective contraception
- treatment with atorvastatin at 40 or 80 mg / d for more than 3 months for primary prevention or secondary prevention at more than 3 months of the acute event (stroke, acute coronary syndrome) with or without ezetimibe (Ezetrol® monotherapy or in the form of associated with atorvastatin Liptruzet® 10/40 or 10/80)
- with a Body Mass Index (BMI) ≥28 kg / m2 and at least one other risk factor for statin-dependent diabetes among the following 4:
- affiliated to a social security scheme
Key exclusion criteria (25 listed)
- General criteria:
- Subject with unstable medical or psychological conditions that, in the opinion of the investigator, could lead the subject to be non-compliant or uncooperative during the study or could compromise the safety or participation of the subject under study L.1121-6, L.1121-8, L.1121-9 and L1122-1-2 of the Public Health Code).
- Major subjects under guardianship or deprived of their liberty by judicial or administrative decision.
- Plan for weight loss during the previous 3 months, current or future
- Dietary supplements for weight loss (based on plant extracts, algae, pre- and probiotics) in the previous 3 months or in progress
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 |
|---|---|---|
| citrulline supplementation2.5 g per os of citrulline on the morning and the evening (5 g/ jour) during 4 weeks. | Dietary supplement | citrulline |
| placebo supplementation2.5 g of the product in the morning and in the evening during 4 weeks. | Dietary supplement | Placebo |
| glucose tolerance test2 exploration mornings distant from 28 days (before and after citrulline) will allow carrying out an oral glucose tolerance test of 2 hours (75 g glucose per os) | Procedure or surgery | Placebo, citrulline |
Primary outcome
difference in the area under the curve of the glycemic response during a 75 g glucose tolerance test between the end and the beginning of citrulline supplementation versus placebo
Time frame: 4 weeks
3 secondary outcomes
Difference in the index of insulin sensitivity determined during Oral Glucose Tolerance Test (OGTT) performed at the end and before the supplementation in citrulline versus placebo
Time frame: 4 weeks
Difference in the index of insulin secretion determined during OGTT performed at the end and before the supplementation in citrulline versus placebo
Time frame: 4 weeks
occurrence of adverse events and serious adverse events for assessment of tolerability
Time frame: assessed up 8 weeks
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 10 Apr 2023.
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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.
Sybil Charriere, MD principal investigator
Hospices Civils de Lyon Endocrinology and diabetology service, Louis Pradel Hospital
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing citrulline supplementation and glucose tolerance test in people with Atorvastatin, run by Hospices Civils de Lyon at 1 site 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 10 inclusion and 25 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 10 Apr 2023. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site 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.
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?
difference in the area under the curve of the glycemic response during a 75 g glucose tolerance test between the end and the beginning of citrulline supplementation versus placebo (time frame: 4 weeks). 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 10 Apr 2023.