Clinical trial NCT04923555: 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
Official title: 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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Metabolic Syndrome
Predisposition to Cardiovascular Disease
Keywords: Metabolic syndrome
Endothelial function
Vegetable proteins
Arginine
Cysteine
Leucine
Nutrition assessment
Nutrition physiological phenomena
Lead sponsor: University Hospital, Clermont-Ferrand
Sponsor class: OTHER
First posted: 2021-06-11
Enrollment: 33
Sex: ALL
Minimum age (years): 65
Standard ages: OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

Detailed description: 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.

Eligibility criteria: 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

Primary outcomes:
measure: Brachial artery Flow Mediated Dilation (FMD)
timeFrame: Day 0 (V1) at T-30min
measure: Brachial artery Flow Mediated Dilation (FMD)
timeFrame: Day 0 (V1) at T180min
measure: Brachial artery Flow Mediated Dilation (FMD)
timeFrame: Day 0 (V1) at T300min
measure: Brachial artery Flow Mediated Dilation (FMD)
timeFrame: Day 28 (V2) at T-30min
measure: Brachial artery Flow Mediated Dilation (FMD)
timeFrame: Day 28 (V2) at T180min
measure: Brachial artery Flow Mediated Dilation (FMD)
timeFrame: Day 28 (V2) at T300min
measure: Brachial artery Flow Mediated Dilation (FMD)
timeFrame: Day 56 (V3) at T-30min
measure: Brachial artery Flow Mediated Dilation (FMD)
timeFrame: Day 56 (V3) at T180min
measure: Brachial artery Flow Mediated Dilation (FMD)
timeFrame: Day 56 (V3) at T300min
Secondary outcomes:
measure: Rest flow by Flowmetry Laser Doppler (FLD)
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Occlusion area by FLD
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Hyperaemia area by FLD
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Hyperaemia area / occlusion area ratio by FLD
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Maximal flow by FLD
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Hyperaemia half time by FLD
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Reactive Hyperemia - Peripheral Arterial Tonometry (RH-PAT)
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Plasma nitrite dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Urine nitrite dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Plasma nitrate dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Urine nitrate dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Plasma creatinine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Urine creatinine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Plasma malondialdehyde (MDA) dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Urine malondialdehyde (MDA) dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Plasma asymmetric dimethylarginine (ADMA) dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Urine asymmetric dimethylarginine (ADMA) dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Plasma symmetric dimethylarginine (SDMA) dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Urine symmetric dimethylarginine (SDMA) dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Plasma acetyl-lysine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3)
measure: Urine symmetric acetyl-lysine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma N-epsilon-carboxy-methyl lysine (CML) dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine N-epsilon-carboxy-methyl lysine (CML) dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma N-epsilon-carboxy-ethyl lysine (CEL) dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine N-epsilon-carboxy-ethyl lysine (CEL) dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma alanine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine alanine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma arginine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine arginine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma asparagine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine asparagine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma aspartic acid dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine aspartic acid dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma cysteine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine cysteine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma glutamic acid dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine glutamic acid dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma glutamine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine glutamine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma glycine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine glycine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma histidine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine histidine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma isoleucine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine isoleucine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma leucine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine leucine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma lysine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine lysine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma methionine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine methionine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma phenylalanine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine phenylalanine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma proline dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine proline dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma serine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine serine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma threonine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine threonine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma tryptophan dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine tryptophan dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma tyrosine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine tyrosine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma valine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Urine valine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma Interleukin 6 (IL-6) dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma Interleukin 1 bêta (IL-1β) dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma Monocyte Chemoattractant Protein-1 (MCP-1) dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma Tumor Necrosis Factor alpha (TNFα) dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma InterCellular Adhesion Molecule 1 (ICAM-1) dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma E-Selectine dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Transcriptome Sequencing of Peripheral Blood Mononuclear Cells
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Metabolome Sequencing of Plasma
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma Glucose dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma triglycerides dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Plasma insulin dosage
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: blood Peripheral Blood Mononuclear Cells (PBMC) count
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: PBMC production of Reactive Oxygen Species (ROS)
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
measure: Questionnaire of acceptability
timeFrame: Day 0 (V1), Day 28 (V2), Day 56 (V3).
Other outcomes:
Locations:
city: Clermont-Ferrand
country: France
facility: CHU clermont-ferrand
Study officials:
affiliation: University Hospital, Clermont-Ferrand
name: Gisèle PICKERING
role: PRINCIPAL_INVESTIGATOR
References: