Nutritional Transitions to More Plant Proteins and Less Animal Proteins: Understanding the Induced Metabolic Reorientations and Searching for Their Biomarkers (ProVegOmics)

Study Overview
=================
Brief Summary
-----------------
The dietary shift from animal to plant protein sources is one of the key aspects of the nutritional transition towards more sustainable food system and diets. However the metabolic implication of this shift in protein sources are still poorly understood. This project aims to characterize and understand the metabolic orientations specifically induced by animal and vegetable dietary proteins, in order to better analyze the metabolic reorientations that would result from the expected increase in the share of plant proteins in different dietary contexts, especially those of the Western type, often associated with the development of metabolic deregulations (obesity and cardiometabolic risk).

Detailed Description
-----------------
The main objectives of this project are: Characterize the metabolic adaptations induced by animal or plant protein diets and their repercussions in terms of physiology and health. Characterize the medium-term metabolomic signatures induced by this shift in dietary protein sources Validate, in a human population, biomarkers of dietary animal or plant proteins, previously identified in pre-clinical studies. This clinical trial is open, monocentric, controlled, randomized, with a cross experimental design. 20 men or postmenopausal women will follow for 4 weeks a controlled diet with a protein fraction constituted mainly from animal or vegetal sources. After a 2-week washout period(+21D/-7D), they will follow another 4 week of controlled diet with predominantly animal or plant protein depending on 1st intervention period diet. At the end of each intervention period, a post-prandial exploration will be conducted with the administration of a high-fat, high-sugar meal and subsequent blood and urine sampling. The order in which participants will received the two diets will be randomized.

Official Title
-----------------
Nutritional Transitions to More Plant Proteins and Less Animal Proteins: Understanding the Induced Metabolic Reorientations and Searching for Their Biomarkers

Conditions
-----------------
Metabolic Syndrome, Hypertriglyceridemia, Fasting Blood Sugar Above Normal, Lower Than Standard HDL-cholesterol Level, Slightly Elevated Blood Pressure

Intervention / Treatment
-----------------
* Behavioral: Diets with either predominantly animal protein sources.
* Behavioral: Diets with predominantly plant protein sources


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: BMI between 25 and 35 kh/m² (terminals included) Waist circumference ≥ 94 cm for men and ≥80 cm for women at the choice, one of the following criteria: Triglyceridemia > 1.49g/L, fasting blood glucose≥ 5.6 mmol/L , a HDL cholesterol <1.03mmol/L for men or <1.29 mmol/L for women , systolic blood pressure≥ 130 mmHg or diastolic≥ 85 mmHg . Exclusion Criteria: Systolic blood pressure > 150mmHg or diastolic blood pressure > 90mmHg pathology and medical treatment diabetes Smoking > 4 cigarettes /day Alcohol consumption > 2 glasses/day Antibiotics taken during the last 3 months before the clinical trial Specific diets

Ages Eligible for Study
-----------------
Minimum Age: 25 Years
Maximum Age: 55 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hypertriglyceridimic/blood sugar/HDLcholesterol/blood pressure waist phenotype/animal protein source<br>20 men or postmenopausal women between 25 and 55 years old with a high waist circumference and at the choice, one of the following criteria high triglyceridemia, blood sugar above standards,a lower than standard HDL-cholesterol level,slightly elevated blood pressure receiving diets with predominantly animal protein sources | Behavioral: Diets with either predominantly animal protein sources.<br>* 20 men or postmenopausal women will follow for 4 weeks a controlled diet with a protein fraction constituted mainly from animal sources. At the end of the intervention period, a post-prandial exploration will be conducted with the administration of a high-fat, high-sugar meal and subsequent blood and urine sampling.<br>|
| Experimental: Hypertriglyceridimic/blood sugar/HDLcholesterol/blood pressure waist phenotype/plant protein source<br>20 men or postmenopausal women between 25 and 55 years old with a high waist circumference and at the choice, one of the following criteria high triglyceridemia, blood sugar above standards,a lower than standard HDL-cholesterol level,slightly elevated blood pressure receiving diets with predominantly plant protein sources | Behavioral: Diets with predominantly plant protein sources<br>* 20 men or postmenopausal women will follow for 4 weeks a controlled diet with a protein fraction constituted mainly from vegetal sources. At the end of the intervention period, a post-prandial exploration will be conducted with the administration of a high-fat, high-sugar meal and subsequent blood and urine sampling.<br>|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| changes of blood metabolomics | the plasma metabolome will be determined by Liquid Chromatography - Mass Spectrometry | day 0 | 
| changes of blood metabolomics | the plasma metabolome will be determined by Liquid Chromatography - Mass Spectrometry | day 14 | 
| changes of blood metabolomics | the plasma metabolome will be determined by Liquid Chromatography - Mass Spectrometry | day 28 | 
| changes of blood metabolomics | the plasma metabolome will be determined by Liquid Chromatography - Mass Spectrometry | day 29 | 
| changes of blood metabolomics | the plasma metabolome will be determined by Liquid Chromatography - Mass Spectrometry | day 42 | 
| changes of blood metabolomics | the plasma metabolome will be determined by Liquid Chromatography - Mass Spectrometry | day 56 | 
| changes of blood metabolomics | the plasma metabolome will be determined by Liquid Chromatography - Mass Spectrometry | day 70 | 
| changes of blood metabolomics | the plasma metabolome will be determined by Liquid Chromatography - Mass Spectrometry | day 71 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Changes of urine metabolomics | the urine metabolome will be determined by Liquid Chromatography - Mass Spectrometry | day 0 | 
| Changes of urine metabolomics | the urine metabolome will be determined by Liquid Chromatography - Mass Spectrometry | day 14 | 
| Changes of urine metabolomics | the urine metabolome will be determined by Liquid Chromatography - Mass Spectrometry | day 28 | 
| Changes of urine metabolomics | the urine metabolome will be determined by Liquid Chromatography - Mass Spectrometry | day 29 | 
| Changes of urine metabolomics | the urine metabolome will be determined by Liquid Chromatography - Mass Spectrometry | day 42 | 
| Changes of urine metabolomics | the urine metabolome will be determined by Liquid Chromatography - Mass Spectrometry | day 56 | 
| Changes of urine metabolomics | the urine metabolome will be determined by Liquid Chromatography - Mass Spectrometry | day 70 | 
| Changes of urine metabolomics | the urine metabolome will be determined by Liquid Chromatography - Mass Spectrometry | day 71 | 
| Changes in blood glucose | The glucose concentrations will be determined by the blood samples taken by ELISA | day 0 | 
| Changes in blood glucose | The glucose concentrations will be determined by the blood samples taken by ELISA | day 14 | 
| Changes in blood glucose | The glucose concentrations will be determined by the blood samples taken by ELISA | day 28 | 
| Changes in blood glucose | The glucose concentrations will be determined by the blood samples taken by ELISA | day 29 | 
| Changes in blood glucose | The glucose concentrations will be determined by the blood samples taken by ELISA | day 42 | 
| Changes in blood glucose | The glucose concentrations will be determined by the blood samples taken by ELISA | day 56 | 
| Changes in blood glucose | The glucose concentrations will be determined by the blood samples taken by ELISA | day 70 | 
| Changes in blood glucose | The glucose concentrations will be determined by the blood samples taken by ELISA | day 71 | 
| Changes in blood insulin | The insulin concentrations will be determined in the blood samples and measured by ELISA | day 0 | 
| Changes in blood insulin | The insulin concentrations will be determined in the blood samples and measured by ELISA | day 14 | 
| Changes in blood insulin | The insulin concentrations will be determined in the blood samples and measured by ELISA | day 28 | 
| Changes in blood insulin | The insulin concentrations will be determined in the blood samples and measured by ELISA | day 29 | 
| Changes in blood insulin | The insulin concentrations will be determined in the blood samples and measured by ELISA | day 42 | 
| Changes in blood insulin | The insulin concentrations will be determined in the blood samples and measured by ELISA | day 56 | 
| Changes in blood insulin | The insulin concentrations will be determined in the blood samples and measured by ELISA | day 70 | 
| Changes in blood insulin | The insulin concentrations will be determined in the blood samples and measured by ELISA | day 71 | 
| Changes in blood cholesterol | The cholesterol concentrations will be determined in the blood samples taken | day 0 | 
| Changes in blood cholesterol | The cholesterol concentrations will be determined in the blood samples taken | day 14 | 
| Changes in blood cholesterol | The cholesterol concentrations will be determined in the blood samples taken | day 28 | 
| Changes in blood cholesterol | The cholesterol concentrations will be determined in the blood samples taken | day 29 | 
| Changes in blood cholesterol | The cholesterol concentrations will be determined in the blood samples taken | day 42 | 
| Changes in blood cholesterol | The cholesterol concentrations will be determined in the blood samples taken | day 56 | 
| Changes in blood cholesterol | The cholesterol concentrations will be determined in the blood samples taken | day 70 | 
| Changes in blood cholesterol | The cholesterol concentrations will be determined in the blood samples taken | day 71 | 
| Changes in blood triglycerides | The triglycerides concentrations will be determined in the blood samples taken | day 0 | 
| Changes in blood triglycerides | The triglycerides concentrations will be determined in the blood samples taken | day 14 | 
| Changes in blood triglycerides | The triglycerides concentrations will be determined in the blood samples taken | day 28 | 
| Changes in blood triglycerides | The triglycerides concentrations will be determined in the blood samples taken | day 29 | 
| Changes in blood triglycerides | The triglycerides concentrations will be determined in the blood samples taken | day 42 | 
| Changes in blood triglycerides | The triglycerides concentrations will be determined in the blood samples taken | day 56 | 
| Changes in blood triglycerides | The triglycerides concentrations will be determined in the blood samples taken | day 70 | 
| Changes in blood triglycerides | The triglycerides concentrations will be determined in the blood samples taken | day 71 | 
| changes in blood IL-6 | The IL-6 concentrations will be determined in the blood samples taken | day 0 | 
| changes in blood IL-6 | The IL-6 concentrations will be determined in the blood samples taken | day 14 | 
| changes in blood IL-6 | The IL-6 concentrations will be determined in the blood samples taken | day 28 | 
| changes in blood IL-6 | The IL-6 concentrations will be determined in the blood samples taken | day 29 | 
| changes in blood IL-6 | The IL-6 concentrations will be determined in the blood samples taken | day 42 | 
| changes in blood IL-6 | The IL-6 concentrations will be determined in the blood samples taken | day 56 | 
| changes in blood IL-6 | The IL-6 concentrations will be determined in the blood samples taken | day 70 | 
| changes in blood IL-6 | The IL-6 concentrations will be determined in the blood samples taken | day 71 | 
| changes in blood IL-10 | The IL-10 concentrations will be determined in the blood samples taken | day 0 | 
| changes in blood IL-10 | The IL-10 concentrations will be determined in the blood samples taken | day 14 | 
| changes in blood IL-10 | The IL-10 concentrations will be determined in the blood samples taken | day 28 | 
| changes in blood IL-10 | The IL-10 concentrations will be determined in the blood samples taken | day 29 | 
| changes in blood IL-10 | The IL-10 concentrations will be determined in the blood samples taken | day 42 | 
| changes in blood IL-10 | The IL-10 concentrations will be determined in the blood samples taken | day 56 | 
| changes in blood IL-10 | The IL-10 concentrations will be determined in the blood samples taken | day 70 | 
| changes in blood IL-10 | The IL-10 concentrations will be determined in the blood samples taken | day 71 | 
| changes in blood CRP | The CRP concentrations will be determined in the blood samples taken | Day 0 | 
| changes in blood CRP | The CRP concentrations will be determined in the blood samples taken | Day 14 | 
| changes in blood CRP | The CRP concentrations will be determined in the blood samples taken | Day 28 | 
| changes in blood CRP | The CRP concentrations will be determined in the blood samples taken | Day 29 | 
| changes in blood CRP | The CRP concentrations will be determined in the blood samples taken | Day 42 | 
| changes in blood CRP | The CRP concentrations will be determined in the blood samples taken | Day 56 | 
| changes in blood CRP | The CRP concentrations will be determined in the blood samples taken | Day 70 | 
| changes in blood CRP | The CRP concentrations will be determined in the blood samples taken | Day 71 | 
| measure of protein synthesis by isotopic labelling | measurement of protein synthesis using deuterium labelling water | Day 28 | 
| measure of protein synthesis by isotopic labelling | measurement of protein synthesis using deuterium labelling water | Day 29 | 
| measure of protein synthesis by isotopic labelling | measurement of protein synthesis using deuterium labelling water | Day 70 | 
| measure of protein synthesis by isotopic labelling | measurement of protein synthesis using deuterium labelling water | Day 71 | 
| Measure of lipogenesis de novo by isotopic labelling | measurement of lipogenesis using deuterium labelling water | Day 28 | 
| Measure of lipogenesis de novo by isotopic labelling | measurement of lipogenesis using deuterium labelling water | Day 29 | 
| Measure of lipogenesis de novo by isotopic labelling | measurement of lipogenesis using deuterium labelling water | Day 70 | 
| Measure of lipogenesis de novo by isotopic labelling | measurement of lipogenesis using deuterium labelling water | Day 71 | 
| Changes in vascular function | will be determined by measuring minimal and maximal diameter of brachial artery in mm and the percentage of dilatation using the Flow-Mediated Dilatation GE echographer | Day 0 | 
| Changes in vascular function | will be determined by measuring minimal and maximal diameter of brachial artery in mm and the percentage of dilatation using the Flow-Mediated Dilatation GE echographer | Day 28 | 
| Changes in vascular function | will be determined by measuring minimal and maximal diameter of brachial artery in mm and the percentage of dilatation using the Flow-Mediated Dilatation GE echographer | Day 42 | 
| Changes in vascular function | will be determined by measuring minimal and maximal diameter of brachial artery in mm and the percentage of dilatation using the Flow-Mediated Dilatation GE echographer | Day 70 | 
| Changes in microcirculation | will be determined measuring resting state and maximal flow by Flow Laser Doppler Periflux 5000 | Day 0 | 
| Changes in microcirculation | will be determined measuring resting state and maximal flow by Flow Laser Doppler Periflux 5000 | Day 28 | 
| Changes in microcirculation | will be determined measuring resting state and maximal flow by Flow Laser Doppler Periflux 5000 | Day 42 | 
| Changes in microcirculation | will be determined measuring resting state and maximal flow by Flow Laser Doppler Periflux 5000 | Day 70 | 
| Changes in mRNA (transcriptomics) derived from Peripheral Blood Monocellular Cells (PBMC) | will be measured by qPCR | Day 0 | 
| Changes in mRNA (transcriptomics) derived from Peripheral Blood Monocellular Cells (PBMC) | will be measured by qPCR | Day 14 | 
| Changes in mRNA (transcriptomics) derived from Peripheral Blood Monocellular Cells (PBMC) | will be measured by qPCR | Day 28 | 
| Changes in mRNA (transcriptomics) derived from Peripheral Blood Monocellular Cells (PBMC) | will be measured by qPCR | Day 29 | 
| Changes in mRNA (transcriptomics) derived from Peripheral Blood Monocellular Cells (PBMC) | will be measured by qPCR | Day 42 | 
| Changes in mRNA (transcriptomics) derived from Peripheral Blood Monocellular Cells (PBMC) | will be measured by qPCR | Day 56 | 
| Changes in mRNA (transcriptomics) derived from Peripheral Blood Monocellular Cells (PBMC) | will be measured by qPCR | Day 70 | 
| Changes in mRNA (transcriptomics) derived from Peripheral Blood Monocellular Cells (PBMC) | will be measured by qPCR | Day 71 | 
| Changes in body composition | will be determined using bioelectric impendence analysis, Quad Scan. | Day 0 | 
| Changes in body composition | will be determined using bioelectric impendence analysis, Quad Scan. | Day 28 | 
| Changes in body composition | will be determined using bioelectric impendence analysis, Quad Scan. | Day 42 | 
| Changes in body composition | will be determined using bioelectric impendence analysis, Quad Scan. | Day 70 | 
| Changes of the microbiota (stool samples) | will be determined by the identification of bacterial biodiversity by a genetic sequencing analysis of bacterial DNA | day 0 | 
| Changes of the microbiota (stool samples) | will be determined by the identification of bacterial biodiversity by a genetic sequencing analysis of bacterial DNA | day 14 | 
| Changes of the microbiota (stool samples) | will be determined by the identification of bacterial biodiversity by a genetic sequencing analysis of bacterial DNA | day 28 | 
| Changes of the microbiota (stool samples) | will be determined by the identification of bacterial biodiversity by a genetic sequencing analysis of bacterial DNA | day 29 | 
| Changes of the microbiota (stool samples) | will be determined by the identification of bacterial biodiversity by a genetic sequencing analysis of bacterial DNA | day 42 | 
| Changes of the microbiota (stool samples) | will be determined by the identification of bacterial biodiversity by a genetic sequencing analysis of bacterial DNA | day 56 | 
| Changes of the microbiota (stool samples) | will be determined by the identification of bacterial biodiversity by a genetic sequencing analysis of bacterial DNA | day 70 | 
| Changes of the microbiota (stool samples) | will be determined by the identification of bacterial biodiversity by a genetic sequencing analysis of bacterial DNA | day 71 | 
| Food statement at inclusion | using 3 days food log before day 0 | day 0 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
Metabolomics, Plant Proteins, Dietary, Meat Proteins, Dietary Proteins, Metabolic Syndrome, Hypertriglyceridemia, Waist Circumference