Effect of Arginine Supplementation in the Metabolic Syndrome

Overweight Clinical Trial

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.

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02354794
• Other study ID #: FRMA13-1
• Secondary ID: 2013-A01043-42
• Status: Completed
• Phase: N/A
• First received: September 24, 2014
• Last updated: January 29, 2015
• Start date: February 2014
• Est. completion date: September 2014

Study information

• Verified date: January 2015
• Source: Institut National de la Recherche Agronomique
• Contact: n/a
• Is FDA regulated: No
• Health authority: France: Agence Nationale de Sécurité du Médicament et des produits de santéFrance: Committee for the Protection of Personnes
• Study type: Interventional

Clinical Trial 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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 36
• Est. completion date: September 2014
• Est. primary completion date: May 2014
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 60 Years

Eligibility

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.

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor)

Related Conditions & MeSH terms

• Hypertriglyceridemic Waist
• Metabolic Syndrome X
• Overweight

Intervention

Dietary Supplement:
• One form of arginine
3 capsules containing 0.5g of one form of L-arginine (1.5g) 3 times daily (4.5g per day) for 1 month
• placebo
3 capsules containing 0.5g cellulose (non active product) 3 times daily (4.5g per day) for 1 month

Locations

Country	Name	City	State
France	Centre de Recherche sur Volontaires (CRV), Hospital Avicenne	Bobigny	Ile-de-France

Sponsors (4)

Lead Sponsor	Collaborator
Institut National de la Recherche Agronomique	Adeprina, Hospital Avicenne, Institut de Recherche Pierre Fabre

Country where clinical trial is conducted

France, 

References & Publications (74)

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* Note: There are 74 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Physiological assessment of endothelial function in postprandial and fasting (Endothelial function was assessed by flow-mediated dilation (FMD) and peripheral arterial tonometry (EndoPAT)	Endothelial function was assessed by flow-mediated dilation (FMD) and peripheral arterial tonometry (EndoPAT).; FMD technique was used during the fasting test. The RHI measurements were performed the morning fasting and 2, 4, and 6 hours after administration of the high-fat meal, in the case of exploration days after supplementation. In terms of the 4h measurement, it was coupled to a FMD assessment.; FMD was calculated as the percentage change in artery diameter at peak dilation compared with baseline and is reported as a percentage.; The Reactive Hyperemia Index (RHI) was calculated as the ratio of the average pulse wave amplitude during hyperemia (60 to 120 s of the postocclusion period) to the average pulse wave amplitude during baseline in the occluded hand divided by the same values in the control hand and then multiplied by a baseline correction factor.	Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment	No
Primary	Evaluation of plasma vascular cell adhesion molecule-1 (VCAM-1) of endothelial function in postprandial and fasting	Fasting plasma concentrations of VCAM-1 will be determined using two custom mixed assay kits with antibody-coated beads using the Luminex xMAP technology platform for multiplexing of immunochemical bioassays.	Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment	No
Primary	Evaluation of plasma intercellular adhesion molecule (ICAM-1) of endothelial function in postprandial and fasting	Fasting plasma concentrations of ICAM-1 will be determined using two custom mixed assay kits with antibody-coated beads using the Luminex xMAP technology platform for multiplexing of immunochemical bioassays.	Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment	No
Primary	Evaluation of plasma E-Selectin of endothelial function in postprandial and fasting	Fasting plasma concentrations E-Selectin will be determined using two custom mixed assay kits with antibody-coated beads using the Luminex xMAP technology platform for multiplexing of immunochemical bioassays.	Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment	No
Primary	Evaluation of plasma P-Selectin of endothelial function in postprandial and fasting	Fasting plasma concentrations P-Selectin will be determined using two custom mixed assay kits with antibody-coated beads using the Luminex xMAP technology platform for multiplexing of immunochemical bioassays.	Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment	No
Primary	Evaluation of plasma Plasminogen activator inhibitor-1 (PAI-1) of endothelial function in postprandial and fasting	Fasting plasma concentrations of PAI-1) will be determined using two custom mixed assay kits with antibody-coated beads using the Luminex xMAP technology platform for multiplexing of immunochemical bioassays.	Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment	No
Primary	Evaluation of plasma C-reactive protein (CRP) of endothelial function in postprandial and fasting	Fasting plasma concentrations of CRP will be determined using two custom mixed assay kits with antibody-coated beads using the Luminex xMAP technology platform for multiplexing of immunochemical bioassays.	Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment	No
Primary	Evaluation of plasma Endothelin-1 of endothelial function in postprandial and fasting	Fasting plasma concentrations of Endothelin-1 will be determined using two custom mixed assay kits with antibody-coated beads using the Luminex xMAP technology platform for multiplexing of immunochemical bioassays.	Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment	No
Secondary	Asymmetric Dimethyl-L-Arginine (ADMA) measurement	- Fasting ADMA concentrations were measured by an enzyme-linked immunosorbent assay.	Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment	No
Secondary	Amino acids measurement	Fasting amino acids contents was assayed by High-performance liquid chromatography (HPLC).	Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment	No
Secondary	Nitrite measurement	Fasting nitrite were analyzed by Gas chromatography-mass spectrometry (GC-MS).	Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment	No
Secondary	Complete blood count (CBC) analysis	Fasting and postprandial complete blood count (CBC) (was assayed using "classical clinical biochemical analyzers".	Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment	No
Secondary	Insulin and glucose measurement	The fasting insulin and the fasting and postprandial glucose were assayed using "classical clinical biochemical analyzers".	Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment	No
Secondary	Lipid profile analysis	- The fasting lipid profile (triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol) and the postprandial evolution of triglycerides were measured and were assayed using "classical clinical biochemical analyzers".	Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment	No
Secondary	Metabolomic analysis	Fasting metabolomic analysis with metabolomic approaches	Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment	No