Effect of Arginine Supplementation in the Metabolic Syndrome

January 29, 2015 updated by: Robert Benamouzig, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement

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.

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

Study Overview

Status

Completed

Conditions

Intervention / Treatment

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.

Study Type

Interventional

Enrollment (Actual)

36

Phase

  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • France
    • Ile-de-France
      • Bobigny, Ile-de-France, France, 93000
        • Centre de Recherche sur Volontaires (CRV), Hospital Avicenne

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

18 years to 60 years (Adult)

Accepts Healthy Volunteers

Yes

Genders Eligible for Study

All

Description

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 Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: Triple

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Experimental: Healthy subjects with 'hypertriglyceridemic waist'

Subjects with overweight, elevated waist circumference and elevated fasting triglyceridemia.

Intervention: see below
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
Dietary supplement: placebo
3 capsules containing 0.5g cellulose (non active product) 3 times daily (4.5g per day) for 1 month

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Physiological assessment of endothelial function in postprandial and fasting (Endothelial function was assessed by flow-mediated dilation (FMD) and peripheral arterial tonometry (EndoPAT)
Time Frame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment

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
Evaluation of plasma vascular cell adhesion molecule-1 (VCAM-1) of endothelial function in postprandial and fasting
Time Frame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
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
Evaluation of plasma intercellular adhesion molecule (ICAM-1) of endothelial function in postprandial and fasting
Time Frame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
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
Evaluation of plasma E-Selectin of endothelial function in postprandial and fasting
Time Frame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
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
Evaluation of plasma P-Selectin of endothelial function in postprandial and fasting
Time Frame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
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
Evaluation of plasma Plasminogen activator inhibitor-1 (PAI-1) of endothelial function in postprandial and fasting
Time Frame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
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
Evaluation of plasma C-reactive protein (CRP) of endothelial function in postprandial and fasting
Time Frame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
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
Evaluation of plasma Endothelin-1 of endothelial function in postprandial and fasting
Time Frame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
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

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Asymmetric Dimethyl-L-Arginine (ADMA) measurement
Time Frame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
- 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
Amino acids measurement
Time Frame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
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
Nitrite measurement
Time Frame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
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
Complete blood count (CBC) analysis
Time Frame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
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
Insulin and glucose measurement
Time Frame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
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
Lipid profile analysis
Time Frame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
- 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
Metabolomic analysis
Time Frame: Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment
Fasting metabolomic analysis with metabolomic approaches
Before the supplementation at day 0 and after the supplementation (1month after) at day 29 for each treatment

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement

Collaborators

Hospital Avicenne
Adeprina
Institut de Recherche Pierre Fabre

Investigators

  • Principal Investigator: Robert Benamouzig, Hospital Avicenne
  • Study Director: François Mariotti, PhD, AgroParisTech

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

February 1, 2014

Primary Completion (Actual)

May 1, 2014

Study Completion (Actual)

September 1, 2014

Study Registration Dates

First Submitted

September 24, 2014

First Submitted That Met QC Criteria

January 29, 2015

First Posted (Estimate)

February 3, 2015

Study Record Updates

Last Update Posted (Estimate)

February 3, 2015

Last Update Submitted That Met QC Criteria

January 29, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FRMA13-1
  • 2013-A01043-42 (Other Identifier: ANSM)

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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