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OverweightNCT02352740

Characterization of the Metabolic Fate of an Oral Arginine Form

A study testing A form Arginine and B form Arginine in people with Overweight and Hypertriglyceridemic Waist, run by Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement at 1 site in France.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record
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Trial 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 Read more about this study

Who is it for?
Ages 18 to 60 yearsHealthy volunteers can take part
Conditions the study is for
Overweight, Hypertriglyceridemic Waist
What is being tested?
A form Arginine and B form Arginine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
32 participants
Where
1 siteFrance
Study dates
Mar 2013to May 2013
Phase
Interventional
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 18 to 60 years
  • All sexes
  • Healthy volunteers accepted
  • Adult

Who may be able to join

  • 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)
  • 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

Who cannot join

  • 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
Show all 26Show fewer
  • 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 :
  • 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

Trial locations and contacts

1 site in 1 country.

France1 site

  • Centre de Recherche sur Volontaires (CRV), Hospital Avicenne

    Bobigny, Île-de-France Region, 93000

Other trials in France

About this study

Official title: 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

Read the 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).

Being tested
A form Arginine, B form Arginine
Keywords
arginine, supplementation, metabolic syndrome, nitric oxide
Medical subject headings
Overweight, Hypertriglyceridemic Waist, Metabolic Syndrome

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • A form ArginineDietary supplement

    3 capsules containing 0.5g of A form of L-arginine (1.5g) 3 times daily (4.5g per day) for 1 week

  • B form ArginineDietary supplement

    3 capsules containing 0.5g of B form of L-arginine (1.5g) 3 times daily (4.5g per day) for 1 week

Study groups in NCT02352740
Study groupRoleWhat they receive
Healthy subjects with 'hypertriglyceridemic waist'ExperimentalSubjects with overweight, elevated waist circumference and elevated fasting triglyceridemia. Intervention : A form arginine and B form arginine
Receives: Dietary Supplement: A form Arginine; Dietary Supplement: B form Arginine
Healthy subjectsExperimentalControl subjects, i.e. without overweight, elevated waist circumference and elevated fasting triglyceridemia. Intervention : A form arginine and B form arginine
Receives: Dietary Supplement: A form Arginine; Dietary Supplement: B form Arginine

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Estimate of total conversion of a dose of oral arginine into NO

    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.

    Measured: Repeated measurement for 24h before (day 0) and after supplementation (day 8) for each treatment

  2. Estimate of kinetic profiles of plasma arginine concentrations over 24 hours

    Plasma AA concentrations were determined using an ultra-performance liquid chromatography-mass spectrometry system as previously described (Haque and al., 2012).

    Measured: Repeated measurement for 24h before (day 0) and after supplementation (day 8) for each treatment

Secondary outcomes (3)

  1. Quantitative analysis of plasma markers of endothelial function

    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).

    Measured: Before supplementation (day 0) and after supplementation (day 8) for each treatment

  2. Estimate of kinetics use of arginine for NO and urea synthesis

    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.

    Measured: Repeated measurement for 24h after supplementation (day 8) for each treament

  3. Other quantitative analysis

    • 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

    Measured: Before supplementation (day 0) and after supplementation (day 8) for each treatment

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted2 Feb 2015 (estimated)
  2. Study startMar 2013
  3. Primary completionMay 2013

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase N/A
Allocation
Randomised
Intervention model
Crossover
Masking
Single blind
Who is masked
Participant
Enrolment
32 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02352740
Sponsor's protocol ID
FRMA12-1
Other IDs
2012-A00755-38
Status last verified
Jan 2015
First submitted
24 Sep 2014
Last updated
2 Feb 2015
Results posted
No
Data monitoring committee
No

Publications

  • Abdelhamed AI, Reis SE, Sane DC, Brosnihan KB, Preli RB, Herrington DM. No effect of an L-arginine-enriched medical food (HeartBars) on endothelial function and platelet aggregation in subjects with hypercholesterolemia. Am Heart J. 2003 Mar;145(3):E15. doi: 10.1067/mhj.2003.160.

    PubMed 12660684

  • Adams MR, Forsyth CJ, Jessup W, Robinson J, Celermajer DS. Oral L-arginine inhibits platelet aggregation but does not enhance endothelium-dependent dilation in healthy young men. J Am Coll Cardiol. 1995 Oct;26(4):1054-61. doi: 10.1016/0735-1097(95)00257-9.

    PubMed 7560599

  • Arsenault BJ, Lemieux I, Despres JP, Wareham NJ, Kastelein JJ, Khaw KT, Boekholdt SM. The hypertriglyceridemic-waist phenotype and the risk of coronary artery disease: results from the EPIC-Norfolk prospective population study. CMAJ. 2010 Sep 21;182(13):1427-32. doi: 10.1503/cmaj.091276. Epub 2010 Jul 19.

    PubMed 20643837

  • 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.

    PubMed 19805654

  • Bai Y, Sun L, Yang T, Sun K, Chen J, Hui R. Increase in fasting vascular endothelial function after short-term oral L-arginine is effective when baseline flow-mediated dilation is low: a meta-analysis of randomized controlled trials. Am J Clin Nutr. 2009 Jan;89(1):77-84. doi: 10.3945/ajcn.2008.26544. Epub 2008 Dec 3.

    PubMed 19056561

  • Balkau B, Vernay M, Mhamdi L, Novak M, Arondel D, Vol S, Tichet J, Eschwege E; D.E.S.I.R. Study Group. The incidence and persistence of the NCEP (National Cholesterol Education Program) metabolic syndrome. The French D.E.S.I.R. study. Diabetes Metab. 2003 Nov;29(5):526-32. doi: 10.1016/s1262-3636(07)70067-8.

    PubMed 14631330

  • Beaumier L, Castillo L, Ajami AM, Young VR. Urea cycle intermediate kinetics and nitrate excretion at normal and "therapeutic" intakes of arginine in humans. Am J Physiol. 1995 Nov;269(5 Pt 1):E884-96. doi: 10.1152/ajpendo.1995.269.5.E884.

    PubMed 7491940

  • Berkowitz DE, White R, Li D, Minhas KM, Cernetich A, Kim S, Burke S, Shoukas AA, Nyhan D, Champion HC, Hare JM; New Collective Author. Arginase reciprocally regulates nitric oxide synthase activity and contributes to endothelial dysfunction in aging blood vessels. Circulation. 2003 Oct 21;108(16):2000-6. doi: 10.1161/01.CIR.0000092948.04444.C7. Epub 2003 Sep 29.

    PubMed 14517171

  • Blackburn P, Lemieux I, Almeras N, Bergeron J, Cote M, Tremblay A, Lamarche B, Despres JP. The hypertriglyceridemic waist phenotype versus the National Cholesterol Education Program-Adult Treatment Panel III and International Diabetes Federation clinical criteria to identify high-risk men with an altered cardiometabolic risk profile. Metabolism. 2009 Aug;58(8):1123-30. doi: 10.1016/j.metabol.2009.03.012. Epub 2009 Jun 18.

    PubMed 19481769

  • Blackburn P, Lemieux I, Lamarche B, Bergeron J, Perron P, Tremblay G, Gaudet D, Despres JP. Hypertriglyceridemic waist: a simple clinical phenotype associated with coronary artery disease in women. Metabolism. 2012 Jan;61(1):56-64. doi: 10.1016/j.metabol.2011.05.017. Epub 2011 Jul 5.

    PubMed 21733531

  • Blum A, Hathaway L, Mincemoyer R, Schenke WH, Kirby M, Csako G, Waclawiw MA, Panza JA, Cannon RO 3rd. Effects of oral L-arginine on endothelium-dependent vasodilation and markers of inflammation in healthy postmenopausal women. J Am Coll Cardiol. 2000 Feb;35(2):271-6. doi: 10.1016/s0735-1097(99)00553-7.

    PubMed 10676669

  • Bode-Boger SM, Boger RH, Galland A, Tsikas D, Frolich JC. L-arginine-induced vasodilation in healthy humans: pharmacokinetic-pharmacodynamic relationship. Br J Clin Pharmacol. 1998 Nov;46(5):489-97. doi: 10.1046/j.1365-2125.1998.00803.x.

    PubMed 9833603

  • Bode-Boger SM, Muke J, Surdacki A, Brabant G, Boger RH, Frolich JC. Oral L-arginine improves endothelial function in healthy individuals older than 70 years. Vasc Med. 2003 May;8(2):77-81. doi: 10.1191/1358863x03vm474oa.

    PubMed 14518608

  • Bode-Boger SM. Effect of L-arginine supplementation on NO production in man. Eur J Clin Pharmacol. 2006;62:91-9.

  • Boger RH. The pharmacodynamics of L-arginine. J Nutr. 2007 Jun;137(6 Suppl 2):1650S-1655S. doi: 10.1093/jn/137.6.1650S.

    PubMed 17513442

Questions about this trial

What is this clinical trial studying?

A study testing A form Arginine and B form Arginine in people with Overweight and Hypertriglyceridemic Waist, run by Institut National de Recherche pour l'Agriculture, l'Alimentation et l'Environnement at 1 site in France.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 26 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: finished, as of the sponsor's last update on 2 Feb 2015. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

Are results available for this study?

The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

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). The study lists 2 primary outcomes in all. It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT02352740, which also lists 63 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Feb 2015.

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