Analysis of the Postprandial Effects of a Vegetable Protein Mixture Rich in Arginine, Cysteine and Leucine on Endothelial Dysfunction and Inflammation at Low Noise in Elderly People With Cardiometabolic Risk

University Hospital, Clermont-Ferrand33 enrolled

Overview

By 2050, the expanding world population will consume two-thirds more animal protein than it consumes today. The increase in chronic diseases associated with the generalization of these consumption patterns tend to understand the place of meat in our diets. All these elements participate to the reduction of animal proteins in favor of vegetable proteins in our food. The elderly are particularly affected by malnutrition, the prevalence of protein-energy malnutrition increasing with age and promoting the onset of morbidities. Without care, it leads to the worsening of physiological phenomena linked to aging such as loss of muscle functionality (sarcopenia) or reduction in bone density (osteoporosis) and increases the risk of falls - the main cause of dependence. However, in France, protein consumption declines significantly with age, even though requirements appear to be greater for the elderly. It is therefore a major challenge for our societies to ensure that the aging of the population and the increase in life expectancy are not synonymous with a reduction in the physical and mental capacities of individuals. Thus, it is essential to ensure that the recommendations for reducing the intake of animal proteins in favor of vegetable proteins can be applied without risk to aging populations, in particular on the human body cardiovascular risk of these populations.

This human dietary intervention study is a double blind, randomized, placebo controlled, cross over trial with 3 arms, carried out on subjects with predisposition to cardiometabolic syndrome (based on weight circumference, blood triglyceride or blood cholesterol, glycemia and hypertension). This study aims to demonstrate transient improvement in vascular endothelial function (with Flow Mediated Dilatation (FMD) as main criteria) with consumption of vegetable proteins (rich in leucine, cysteine and arginine) by comparison with animal proteins and with a control without proteins. The 33 recruited participants will receive the 3 yogurts in a random order. For each subject, the study is divided into 4 visits. To summarize: Visit 1 (D-7) = inclusion, Visit 2 (D0: treatment period N°1), Visit 3 (D28 : treatment period N°2), Visit 4 (D56 : treatment period N°3). The wash-out periods between treatment period (duration: 4 weeks) may be extended until 5 weeks for the convenience of participants. The protocol includes a total of 4 visits to PIC/CIC Inserm 1405 of the Clermont-Fd University Hospital.

Study Type

INTERVENTIONAL

Allocation

Purpose

BASIC_SCIENCE

Interventions

Vegetable proteins (VP) rich in leucine, cystein, arginineBEHAVIORAL

33 volunteers will consume 400 ml of yogurt with vegetable proteins (VP) rich in leucine, cystein and arginine only once during the visit. At the beginning and the end of the intervention, exploration will be conducted at fasted state and at post-prandial state after the administration of vegetable proteins.

Animal proteins (AP)BEHAVIORAL

33 volunteers will consume 400 ml of yogurt with animal proteins (AP) rich in leucine, cystein and arginine only once during the visit. At the beginning and the end of the intervention, exploration will be conducted at fasted state and at post-prandial state after the administration of animal proteins.

No protein (T)BEHAVIORAL

33 volunteers will consume 400 ml of yogurt without any protein (T) rich in leucine, cystein and arginine only once during the visit. At the beginning and the end of the intervention, exploration will be conducted at fasted state and at post-prandial state after the administration of animal proteins.

Eligibility

Sex: ALLMin age: 65 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Man or woman * 65 years old and older (inclusive) * At least 2 of the following 4 cardiometabolic factors: * Waist circumference ≥88 cm for women, and ≥94 cm for men * Fasting triglyceridemia \>1,5 g/L OR HDL level \< 40 mg/dl for men, and \< 50 mg/dl for women * Fasting blood glucose ≥ 100 mg/dl * Systolic blood pressure \>130mmHg ou diastolic \> 85 mm Hg * Accept not to change his lifestyle throughout the study * Accept to consume the same meal the day before exploration days, making sure to exclude non-recommended foods and agreeing to detail its content in a food diary * Ability to give informed consent to participate in research * Affiliation to Social Security Exclusion Criteria: * Acute pathology (unstable or terminal pathology) * Renal failure (clearance \<40 mL / min) * Asthma or chronic respiratory disease * Systolic or diastolic blood pressure in the judgement of the investigator * Diabetic (treated or not) * Treated with chemotherapy * Gastrointestinal, thyroid, cardiac or vascular illness in the judgement of the investigator * Biological examination no compatible with the study in the judgement of the investigator * Medical and/or surgical history no compatible with the study in the judgement of the investigator (previous cardiovascular events) * AgHbS, AcHbc, HCV and HIV positive serology * Concomitant treatment no compatible with the study in the judgement of the investigator * Diet or change in body mass \> 2 kg in the 30 days before the study * Following a diet incompatible with the nutritional protocol (food intolerances, vegans, exclusion of certain food ingredients) * Allergies to any of the components of the test meals * Alcohol consumption\> 2 glasses / day * Current smokers (\> 6 cigarettes per week) * Subjects involved in another clinical trial or being in the exclusion period of another study or having received a total compensation greater than 4,500 euros over the 12 months preceding the start of the trial * Subject benefiting from a legal protection measure (curatorship, guardianship, safeguard of justice) * Refusal to participate

Locations (1)

CHU clermont-ferrand

Clermont-Ferrand, France

Outcomes

Primary Outcomes

Brachial artery Flow Mediated Dilation (FMD)

The endothelial function will be assessed using the non-invasive ultrasound technique of flow mediated dilatation of the brachial artery. FMD measure is the percentage of dilation of brachial artery in response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery realized.

Time frame: Day 0 (V1) at T-30min

Brachial artery Flow Mediated Dilation (FMD)

Time frame: Day 0 (V1) at T180min

Brachial artery Flow Mediated Dilation (FMD)

Time frame: Day 0 (V1) at T300min

Brachial artery Flow Mediated Dilation (FMD)

Time frame: Day 28 (V2) at T-30min

Brachial artery Flow Mediated Dilation (FMD)

Time frame: Day 28 (V2) at T180min

Brachial artery Flow Mediated Dilation (FMD)

Time frame: Day 28 (V2) at T300min

Brachial artery Flow Mediated Dilation (FMD)

Time frame: Day 56 (V3) at T-30min

Brachial artery Flow Mediated Dilation (FMD)

Time frame: Day 56 (V3) at T180min

Brachial artery Flow Mediated Dilation (FMD)

Time frame: Day 56 (V3) at T300min

Secondary Outcomes

Rest flow by Flowmetry Laser Doppler (FLD)

Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the rest flow using laser-Doppler system at the level of the skin of the hand realized between T-30min to T300min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Occlusion area by FLD

Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the occlusion area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement) realized between T-30min to T300min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Hyperaemia area by FLD

Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia area using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement) realized between T-30min to T300min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Hyperaemia area / occlusion area ratio by FLD

Vascular endothelial function in the micro-vascular compartment will be assessed using the ratio hyperaemia area / occlusion area determined by FLD realized between T-30min to T300min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Maximal flow by FLD

Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the maximal flow using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement) realized between T-30min to T300min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Data from ClinicalTrials.gov

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Hyperaemia half time by FLD

Vascular endothelial function in the micro-vascular compartment will be assessed using the measurement of the hyperaemia half time using laser-Doppler system at the level of the skin of the hand by following the response to a reactive hyperaemia induced by the release of a transient occlusion of the brachial artery (same stimulus as for FMD measurement) realized between T-30min to T300min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Reactive Hyperemia - Peripheral Arterial Tonometry (RH-PAT)

Reactive hyperemia index (RHI) assessed by reactive hyperemia-peripheral arterial tonometry (RH-PAT) expressed as a percentage measures pulsatile fluctuations in digital volume in response to a reactive hyperaemia induced by the release of a transient occlusion realized between T-30min to T300min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Plasma nitrite dosage

Determination of nitrite plasma concentration (µmol/L) (a biomarker of endothelial activation) between T-90min to T360min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Urine nitrite dosage

Determination of nitrite urine concentration (µmol/L) (a biomarker of endothelial activation) between T-60min to T250min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Plasma nitrate dosage

Determination of nitrate plasma concentration (µmol/L) (a biomarker of endothelial activation) between T-90min to T360min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Urine nitrate dosage

Determination of nitrate urine concentration (µmol/L) (a biomarker of endothelial activation) between T-60min to T250min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Plasma creatinine dosage

Determination of creatinine plasma concentration (µmol/L) (a biomarker of chronic kidney disease) between T-90min to T360min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Urine creatinine dosage

Determination of creatinine urine concentration (µmol/L) (a biomarker of chronic kidney disease) between T-60min to T250min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Plasma malondialdehyde (MDA) dosage

Determination of MDA plasma concentration (nmol/L) (a biomarker of oxidative stress) between T-90min to T360min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Urine malondialdehyde (MDA) dosage

Determination of MDA urine concentration (nmol/L) (a biomarker of oxidative stress) between T-60min to T250min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Plasma asymmetric dimethylarginine (ADMA) dosage

Determination of ADMA plasma concentration (µmol/L) (a biomarker of cardiovascular disease) between T-90min to T360min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Urine asymmetric dimethylarginine (ADMA) dosage

Determination of ADMA urine concentration (µmol/L) (a biomarker of cardiovascular disease) between T-60min to T250min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Plasma symmetric dimethylarginine (SDMA) dosage

Determination of SDMA plasma concentration (µmol/L) (a biomarker of cardiovascular disease) between T-90min to T360min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Urine symmetric dimethylarginine (SDMA) dosage

Determination of SDMA urine concentration (µmol/L) (a biomarker of cardiovascular disease) between T-60min to T250min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Plasma acetyl-lysine dosage

Determination of acetyl-lysine plasma concentration (µmol/L) (a biomarker of vascular oxidative stress) between T-90min to T360min.

Time frame: Day 0 (V1), Day 28 (V2), Day 56 (V3)

Urine symmetric acetyl-lysine dosage

Determination of acetyl-lysine urine concentration (µmol/L) (a biomarker of vascular oxidative stress) between T-60min to T250min