Working…
COVID-19 is an emerging, rapidly evolving situation.
Get the latest public health information from CDC: https://www.coronavirus.gov.

Get the latest research information from NIH: https://www.nih.gov/coronavirus.
ClinicalTrials.gov
ClinicalTrials.gov Menu

Characterization of the Metabolic Fate of an Oral Arginine Form

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02352740
Recruitment Status : Completed
First Posted : February 2, 2015
Last Update Posted : February 2, 2015
Sponsor:
Collaborators:
Institut de Recherche Pierre Fabre
Hospital Avicenne
Adeprina
Information provided by (Responsible Party):
Robert Benamouzig, Institut National de la Recherche Agronomique

Brief Summary:
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

Condition or disease Intervention/treatment Phase
Overweight Hypertriglyceridemic Waist Dietary Supplement: A form Arginine Dietary Supplement: B form Arginine Not Applicable

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).

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Actual Enrollment : 32 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Single (Participant)
Official Title: Characterization of the Metabolic Fate of an Oral L-arginine Form in Healthy Subjects Featuring Risk Factors Related to the Metabolic Syndrome.
Study Start Date : March 2013
Actual Primary Completion Date : May 2013

Resource links provided by the National Library of Medicine


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




Primary Outcome Measures :
  1. 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.


  2. 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).


Secondary Outcome Measures :
  1. 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).


  2. 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.


  3. 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



Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 60 Years   (Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
Criteria

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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02352740


Locations
Layout table for location information
France
Centre de Recherche sur Volontaires (CRV), Hospital Avicenne
Bobigny, Ile-de-France, France, 93000
Sponsors and Collaborators
Institut National de la Recherche Agronomique
Institut de Recherche Pierre Fabre
Hospital Avicenne
Adeprina
Investigators
Layout table for investigator information
Principal Investigator: Robert Benamouzig Hospital Avicenne
Study Director: François Mariotti, PhD AgroParisTech
Publications:
Alberti KG, Eckel RH, Grundy SM, Zimmet PZ, Cleeman JI, Donato KA, Fruchart JC, James WP, Loria CM, Smith SC Jr; International Diabetes Federation Task Force on Epidemiology and Prevention; Hational Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; International Association for the Study of Obesity. Harmonizing the metabolic syndrome: a joint interim statement of the International Diabetes Federation Task Force on Epidemiology and Prevention; National Heart, Lung, and Blood Institute; American Heart Association; World Heart Federation; International Atherosclerosis Society; and International Association for the Study of Obesity. Circulation. 2009 Oct 20;120(16):1640-5. doi: 10.1161/CIRCULATIONAHA.109.192644. Epub 2009 Oct 5.
Bode-Boger SM. Effect of L-arginine supplementation on NO production in man. Eur J Clin Pharmacol. 2006;62:91-9.
Mariotti F, Huneau JF, Petzke KJ, Szezepanski I, Tomé D, Bos C, Bonnet D. Malgré une assez forte extraction splanchnique pour l'uréogenèse, l'arginine alimentaire, à dose nutritionnelle, est largement, et de façon dose-dépendante, disponible pour les tissus périphériques. Nutr Clin Metab. 2008:22(S1):5.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Layout table for additonal information
Responsible Party: Robert Benamouzig, PU-PH in University Hospitals Paris-Seine-Saint-Denis-APHP-University Hospital Avicenne / Jean Verdier, Institut National de la Recherche Agronomique
ClinicalTrials.gov Identifier: NCT02352740    
Other Study ID Numbers: FRMA12-1
2012-A00755-38 ( Other Identifier: ANSM )
First Posted: February 2, 2015    Key Record Dates
Last Update Posted: February 2, 2015
Last Verified: January 2015
Keywords provided by Robert Benamouzig, Institut National de la Recherche Agronomique:
arginine
supplementation
metabolic syndrome
nitric oxide
Additional relevant MeSH terms:
Layout table for MeSH terms
Hypertriglyceridemic Waist
Overweight
Body Weight
Signs and Symptoms
Metabolic Diseases
Hypertriglyceridemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders