Clinical trial: Citrulline Efficacy to Improve Carbohydrate Metabolism Abnormalities in the Patient Treated With High Doses of Statin (NCT03596684)

Eligibility criteria:
Inclusion Criteria:

          -  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 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.
No condition on gender to be admitted to the trial.
No healthy subjects accepted to join the trial.
Subject must be at least 40 Years old.
Subject must be at most 75 Years

Patient description (medical language): A 50-year-old woman comes to the clinic with intermittent ear discharge and sense of hearing loss on her left ear.  Past medical history is significant for obesity, hyperlipidemia, and diabetes mellitus.  Her medications include Metformin, Atorvastatin and Vit D supplement. Vital signs are normal. BMI is 37. Otoscopy shows a small perforation in the left tympanic membrane and a pearly mass behind the membrane.  Conduction hearing loss is noted in the left ear.  The remainder of the ear, nose, and throat examination is normal.

Patient description (patient's own words): I went to the clinic the other day because I had some fluid in my ear and I felt like I could not hear as well as I used to in my left ear. I'm a 50-year-old woman, and I have been obese for a while now. I have diabetes and cholesterol. I take some medication. I take metformin, atorvastatin, and vitamin D supplements. When I was admitted, my vitals were normal. My BMI is 37. When they looked into my ears, they said that my left tympanic membrane was broken and there was some fluid behind the membrane. During the hearing test, they could assess that my left ear suffers from hearing loss. They also performed ear, nose, and throat examinations that turned out to be normal.

Does the patient match the trial criteria? 1