Clinical trial NCT02354794: Effect of Arginine Supplementation in the Metabolic Syndrome
Official title: Effect of Oral Supplementation With One Form of L-arginine on Vascular Endothelial Function in Healthy Subjects Featuring Risk Factors Related to the Metabolic Syndrome.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Overweight
Hypertriglyceridemic Waist
Keywords: arginine
supplementation
metabolic syndrome
endothelial function
Lead sponsor: Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement
Sponsor class: OTHER
Collaborators: name: Institut de Recherche Pierre Fabre
name: Hospital Avicenne
name: Adeprina
First posted: 2015-02-03
Enrollment: 36
Sex: ALL
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER

Brief summary: The purpose of this study is to determine whether oral supplementation with one form of arginine improves vascular endothelial function in healthy subjects with risk factors associated with the metabolic syndrome

Detailed description: The study is a randomized crossover study including 32 subjects with risk factors associated with metabolic syndrome. In a cross-over design, each subject received oral arginine and placebo, in a randomized order, and were studied the day preceding the first day of administration of arginine (or placebo) and after 4 weeks of arginine (or placebo) supplementation. The two periods of supplementation were separated by a washout period of at least 4 weeks.

The subject were studied in the morning (when before supplementation) and in a whole day (when after supplementation).

The mornings cessions consisted of fasting blood draw and vascular explorations, including a measurement of endothelium-dependent brachial artery reactivity ("Flow mediated dilation"), directly coupled to a measurement of post-ischemic digital reactivity (with the Endo-PAT method), completed by a measurement of non-endothelium-dependent brachial artery reactivity. An analysis of the pulse wave geometry was also performed.

The whole-day cession consisted of the same fasting vascular explorations. Blood tests were performed fasting and repeated 2, 4 and 6 h after ingestion of a high-fat meal (900 kcal). Measurements of Flow mediated dilation was repeated 4h and postischemic digital reactivity were repeated 2, 4 and 6 h after ingestion of the high fat meal.

Eligibility criteria: Inclusion Criteria :

* Age between 18 to 60 years old
* Overweight (BMI between 25 and 30 kg/m²)
* 'Hypertriglyceridemic waist' (waist circumference \> 94cm for men or \> 88cm for women and fasting triglyceride levels \> 150 mg/dL)

Exclusion Criteria :

* Obesity (BMI\> 30 kg / m²)
* Cardiac or vascular diseases
* Diabetes
* Thyroid disease
* Systolic blood pressure \> 150 mmHg or diastolic blood pressure \> 90 mmHg
* Tobacco consumption \> 6 cigarettes per week
* Alcohol consumption\> 2 drinks per day
* Any medication (except contraceptive treatment) or dietary supplement intake that could not be arrested more than a week before the first visit for the duration of the study.
* Persons under guardianship
* Positive Hepatitis B virus (HBV), Hepatitis C virus (HCV) and HIV
* Hemoglobin \< 14 g/dl (for men) or \<12 g / dl (for women)
* Participation in a clinical trial within 6 months preceding the study
* Pregnant and lactating women
* For women, menstrual cycle with a duration different from 28 (± 1) days (the cycle is not controlled by a contraceptive treatment at 28 days, or he does not appear spontaneously with regularity)
* Subjects with allergies to final product components
* Contraindications to arginine intake, namely asthmatics subjects, people prone to herpes, patients with liver cirrhosis and renal failure
* Hypotensive patients for whom the use of nitroglycerin is contraindicated.

Primary outcomes:
measure: Physiological assessment of endothelial function in postprandial and fasting (Endothelial function was assessed by flow-mediated dilation (FMD) and peripheral arterial tonometry (EndoPAT)
timeFrame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
measure: Evaluation of plasma vascular cell adhesion molecule-1 (VCAM-1) of endothelial function in postprandial and fasting
timeFrame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
measure: Evaluation of plasma intercellular adhesion molecule (ICAM-1) of endothelial function in postprandial and fasting
timeFrame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
measure: Evaluation of plasma E-Selectin of endothelial function in postprandial and fasting
timeFrame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
measure: Evaluation of plasma P-Selectin of endothelial function in postprandial and fasting
timeFrame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
measure: Evaluation of plasma Plasminogen activator inhibitor-1 (PAI-1) of endothelial function in postprandial and fasting
timeFrame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
measure: Evaluation of plasma C-reactive protein (CRP) of endothelial function in postprandial and fasting
timeFrame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
measure: Evaluation of plasma Endothelin-1 of endothelial function in postprandial and fasting
timeFrame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
Secondary outcomes:
measure: Asymmetric Dimethyl-L-Arginine (ADMA) measurement
timeFrame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
measure: Amino acids measurement
timeFrame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
measure: Nitrite measurement
timeFrame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
measure: Complete blood count (CBC) analysis
timeFrame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
measure: Insulin and glucose measurement
timeFrame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
measure: Lipid profile analysis
timeFrame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
measure: Metabolomic analysis
timeFrame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
Other outcomes:
Locations:
city: Bobigny
country: France
facility: Centre de Recherche sur Volontaires (CRV), Hospital Avicenne
state: Ile-de-France
Study officials:
affiliation: Hospital Avicenne
name: Robert Benamouzig
role: PRINCIPAL_INVESTIGATOR
affiliation: AgroParisTech
name: François Mariotti, PhD
role: STUDY_DIRECTOR
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