Characterization of the Metabolic Fate of an Oral Arginine Form

January 28, 2015 updated by: Robert Benamouzig, Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement

Characterization of the Metabolic Fate of an Oral L-arginine Form in Healthy Subjects Featuring Risk Factors Related to the Metabolic Syndrome.

The purpose of this study is to compare the metabolic fate of two oral forms of L-Arginine in healthy subjects featuring metabolic syndrome related risk factors

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The study is a randomized crossover study including 16 healthy subjects with risk factors for metabolic syndrome and 16 healthy control subjects. According a double crossover design, each subject received two oral forms of L-arginine (A and B) in random order, and participated in a exploration day on the first day of arginine administration and after one week of supplementation with this arginine form. The two weeks of arginine supplementation were separated by a washout period of 2 weeks at least.

Each exploration extended over 24 hours after administration of the first arginine dose. Blood tests were performed at 0, 0.5, 1, 2, 4, 6, 8, 12, 16, 24 h after administration of the first dose. During explorations after the supplementation period, we also collected urine (0, 2, 4, 8, 12, 24 h after the first dose).

Study Type

Interventional

Enrollment (Actual)

32

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

Healthy subjects with 'Hypertriglyceridemic waist' :

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> 3 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
  • Pregnancy (positive beta-hCG blood test)
  • Positive serology HBsAg AcHbc, 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

Healthy control subjects :

Inclusion Criteria:

  • Age between 18 to 60 years old
  • Normal weight (BMI between 18.5 and 25 kg/m²)
  • Waist circumference < 94cm for men or < 88cm for women and fasting triglyceride levels < 150 mg/dL

Exclusion Criteria :

  • 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> 3 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
  • Pregnancy (positive beta-hCG blood test)
  • Positive serology HBsAg AcHbc, 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

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: Single

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 : A form arginine and B form arginine
Dietary supplement: A form Arginine
3 capsules containing 0.5g of A form of L-arginine (1.5g) 3 times daily (4.5g per day) for 1 week
Dietary supplement: B form Arginine
3 capsules containing 0.5g of B form of L-arginine (1.5g) 3 times daily (4.5g per day) for 1 week
Experimental: Healthy subjects

Control subjects, i.e. without overweight, elevated waist circumference and elevated fasting triglyceridemia.

Intervention : A form arginine and B form arginine
Dietary supplement: A form Arginine
3 capsules containing 0.5g of A form of L-arginine (1.5g) 3 times daily (4.5g per day) for 1 week
Dietary supplement: B form Arginine
3 capsules containing 0.5g of B form of L-arginine (1.5g) 3 times daily (4.5g per day) for 1 week

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Estimate of total conversion of a dose of oral arginine into NO
Time Frame: Repeated measurement for 24h before (day 0) and after supplementation (day 8) for each treatment

This assessment uses labelled arginine ([15N2-(guanido)]-arginine) for the first dose of arginine taken in the morning, and measurements of 15NO3 in urine for 24h.

After administration of 15N-arginine, for each urine collection, we determined the nitrate excretion (from measurement of diuresis and nitrate concentration, by reactive chemiluminescence) and isotope 15N enrichment of nitrate ion (by microdiffusion technique and elementary analyzer connected to an isotope mass spectrometerEA-IRMS), to establish, by the principle of isotopic dilution, the total quantities of nitrate specifically from the ingested arginine. The sum of this excretion relative to the ingested dose determined the relative conversion of ingested arginine into NO.
Repeated measurement for 24h before (day 0) and after supplementation (day 8) for each treatment
Estimate of kinetic profiles of plasma arginine concentrations over 24 hours
Time Frame: Repeated measurement for 24h before (day 0) and after supplementation (day 8) for each treatment
Plasma AA concentrations were determined using an ultra-performance liquid chromatography-mass spectrometry system as previously described (Haque and al., 2012).
Repeated measurement for 24h before (day 0) and after supplementation (day 8) for each treatment

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Quantitative analysis of plasma markers of endothelial function
Time Frame: Before supplementation (day 0) and after supplementation (day 8) for each treatment

Fasting plasma concentrations of vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule (ICAM-1), E-Selectin, P-Selectin, Plasminogen activator inhibitor-1 (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.

In addition, we also have plasma concentrations of nitrite, a marker of of NO production (by reactive chemiluminescence) and other associated markers (3-nitrotyrosine, nitrosothiols, cGMP, in particular ANP, by immunochemistry).
Before supplementation (day 0) and after supplementation (day 8) for each treatment
Estimate of kinetics use of arginine for NO and urea synthesis
Time Frame: Repeated measurement for 24h after supplementation (day 8) for each treament

After administration of 15N-arginine, we measured 15N isotopic enrichment of arginine and citrulline (by mass spectrometry coupled with gas chromatography), of plasma and urinary urea (by separation, by ion exchange, and EA-IRMS) as well as the plasma and urine concentrations in urea. These data and those of arginine and citrulline concentrations provided, by the principle of isotopic dilution, the plasma appearance of ingested arginine and the plasma appearance and urinary excretion of products of its metabolism in NO synthase and arginase ways.

These data were then subjected to a compartmental modeling work to establish the metabolic flow in these ways.
Repeated measurement for 24h after supplementation (day 8) for each treament
Other quantitative analysis
Time Frame: Before supplementation (day 0) and after supplementation (day 8) for each treatment
  • Fasting Asymmetric Dimethyl-L-Arginine (ADMA) concentrations were measured by an enzyme-linked immunosorbent assay.
  • The fasting lipid profile (triglycerides, total cholesterol, HDL-cholesterol, LDL-cholesterol) was measured and were assayed using "classical clinical biochemical analyzers".
  • The fasting insulin and glucose were assayed using "classical clinical biochemical analyzers".
  • Fasting metabolomic analysis
Before supplementation (day 0) and after supplementation (day 8) 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

March 1, 2013

Primary Completion (Actual)

May 1, 2013

Study Registration Dates

First Submitted

September 24, 2014

First Submitted That Met QC Criteria

January 28, 2015

First Posted (Estimate)

February 2, 2015

Study Record Updates

Last Update Posted (Estimate)

February 2, 2015

Last Update Submitted That Met QC Criteria

January 28, 2015

Last Verified

January 1, 2015

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • FRMA12-1
  • 2012-A00755-38 (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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