Clinical Trial: Effect of Arginine Supplementation in the Metabolic Syndrome

Study Status: Completed
Recruit Status: Completed
Study Type: Interventional

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.

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

Detailed Summary:

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.


Sponsor: Institut National de la Recherche Agronomique

Current Primary Outcome:

  • 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.

  • 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 Lu

    Original Primary Outcome: Same as current

    Current Secondary Outcome:

    • 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.
    • 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).
    • 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).
    • 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".
    • 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".
    • 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".
    • 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


    Original Secondary Outcome: Same as current

    Information By: Institut National de la Recherche Agronomique

    Dates:
    Date Received: September 24, 2014
    Date Started: February 2014
    Date Completion:
    Last Updated: January 29, 2015
    Last Verified: January 2015