Citrulline Efficacy to Improve Carbohydrate Metabolism Abnormalities in the Patient Treated With High Doses of Statin

  • STATUS
    Recruiting
  • End date
    Oct 26, 2021
  • participants needed
    24
  • sponsor
    Hospices Civils de Lyon
Updated on 24 January 2021

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. 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 Batrice 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).

Details
Condition Atorvastatin
Treatment Glucose tolerance test, citrulline supplementation, placebo supplementation
Clinical Study IdentifierNCT03596684
SponsorHospices Civils de Lyon
Last Modified on24 January 2021

Eligibility

Yes No Not Sure

Inclusion Criteria

Is your age between 40 yrs and 75 yrs?
Gender: Male or Female
Do you have Atorvastatin?
Do you have any of these conditions: Do you have Atorvastatin??
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 6 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
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

Exclusion Criteria

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
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
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