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Trial record 1 of 2 for:    9036757 [PUBMED-IDS]
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Effect of Arginine Supplementation in the Metabolic Syndrome

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ClinicalTrials.gov Identifier: NCT02354794
Recruitment Status : Completed
First Posted : February 3, 2015
Last Update Posted : February 3, 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 determine whether oral supplementation with one form of arginine improves vascular endothelial function in healthy subjects with risk factors associated with the metabolic syndrome

Condition or disease Intervention/treatment Phase
Overweight Hypertriglyceridemic Waist Dietary Supplement: One form of arginine Dietary Supplement: placebo Not Applicable

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  (Clinical Trial)
Actual Enrollment : 36 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
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.
Study Start Date : February 2014
Actual Primary Completion Date : May 2014
Actual Study Completion Date : September 2014


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




Primary Outcome Measures :
  1. 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.


  2. 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.

  3. 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.

  4. 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.

  5. 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.

  6. 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.

  7. 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.

  8. 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.


Secondary Outcome Measures :
  1. 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.

  2. 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).

  3. 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).

  4. 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".

  5. 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".

  6. 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".

  7. 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



Information from the National Library of Medicine

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

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.

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): NCT02354794


Locations
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
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

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
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: NCT02354794     History of Changes
Other Study ID Numbers: FRMA13-1
2013-A01043-42 ( Other Identifier: ANSM )
First Posted: February 3, 2015    Key Record Dates
Last Update Posted: February 3, 2015
Last Verified: January 2015

Keywords provided by Robert Benamouzig, Institut National de la Recherche Agronomique:
arginine
supplementation
metabolic syndrome
endothelial function

Additional relevant MeSH terms:
Overweight
Metabolic Syndrome X
Hypertriglyceridemic Waist
Body Weight
Signs and Symptoms
Insulin Resistance
Hyperinsulinism
Glucose Metabolism Disorders
Metabolic Diseases
Hypertriglyceridemia
Hyperlipidemias
Dyslipidemias
Lipid Metabolism Disorders