Synergistic Innovative Functional Food Concepts to Neutralize Inflammation for Cardiometabolic Risk Prevention

Study Overview
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Brief Summary
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The aim of the study is to evaluate the synergistic effects of daily consumption of food products fortified with bioactive components (fibres, polyphenols, omega-3, Slow Digestible Starch) for 9 weeks, compared to the daily intake of standard food products on low-grade inflammation in cardiometabolic risk subject. The inflammatory parameters will be assessed in fasting and in postprandial period after the consumption of a hyper-carbohydrate and hyper-lipidic test meal called Flexmeal. A metabolic stress will be induced by a fructose ingestion challenge during the last 6 days of interventional period.

Official Title
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Synergistic Innovative Functional Food Concepts to Neutralize Inflammation for Cardiometabolic Risk Prevention.

Conditions
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Cardiometabolic Risk, Abdominal Obesity

Intervention / Treatment
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* Other: bioactive components fortified food products intake (biscuits and cookies)
* Other: control food products intake (biscuits and cookies)


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy men and women Body Mass Index of 25 to 35 kg/m2 Waist circumference greater than 80 cm for women and than 96 cm for men Daily biscuits consumption Fibers intake <25g/day Exclusion Criteria: Medical history of digestive surgery or disease Large polyphenols food products consumer (cranberries, red berries, coffee, tea, red wine, fruits and vegetables…) Current or recent (<12 weeks) intake of antibiotics or gastro-intestinal medicinal product Current probiotics, prebiotics, fibers complement, and/or any products modulation gut transit Feeding particular diet such as vegetarian diet or hyperprotein diet Current weight loss diet Pregnant or lactating woman or woman who did not use effective contraception Drinking more than 3 glasses of alcohol per day (>30g/day) Smoking more than 5 cigarettes per day

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 65 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: bioactive components fortified food products<br> | Other: bioactive components fortified food products intake (biscuits and cookies)<br>* Volunteers will have to consume daily 100 g of fortified biscuits and cookies instead of those usually consumed during nine weeks. The last week, volunteers will have to consume daily a fructose solution (3g/kg fat free mass)<br>|
| Placebo Comparator: control food products<br> | Other: control food products intake (biscuits and cookies)<br>* Volunteers will have to consume daily 100 g of standard biscuits and cookies instead of those usually consumed during nine weeks. The last week, volunteers will have to consume daily a fructose solution (3g/kg fat free mass)<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline postprandial plasma endotoxemia binding protein kinetics: LBP (lipopolysaccharide-binding protein) and CD14 (Cluster of differentiation 14) | LBP and CD14 proteins will be measured at time 0, 120 and 300 after test meal intake | baseline, 8 and 9 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline fasting and postprandial plasma inflammatory markers: MCP-1, RANTES, IFNγ, IL-6, TNF-α, IL-1β, CRPus, adiponectin | MCP-1 ( monocyte chemotactic protein-1), RANTES (Regulated on activation, normal T expressed and secreted), IFNγ (Interferon γ) , IL-6 (Interleukin 6), TNF-α (Tumor Necrosis Factor α), IL-1β (Interleukin 1β), CRPus, adiponectin will be measured at time 0 and 300 minutes after test meal intake | baseline, 8 and 9 weeks | 
| Change of fasting and postprandial plasma inflammatory endotoxemia LPS (lipopolysaccharide) | LPS will be measured at time 0, 60, 120, 180, 240, 300 after test meal intake | baseline, 8 and 9 weeks | 
| Change from baseline fasting and postprandial plasma endothelial function markers: Human CVD Panel 2, Lipocalin-2/NGAL, Myeloperoxidase, sICAM-1, sVCAM-1, ADAMTS13, D-dimer, GDF-15, Myoglobin, sP-Selectin, Serum Amyloid A | Human CVD Panel 2, Lipocalin-2/NGAL (neutrophil gelatinase-associated lipocalin), Myeloperoxidase, sICAM-1(Soluble Inter-cellular Adhesion Molecule-1), sVCAM-1(Soluble Form of Vascular Cell Adhesion Molecule 1), ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13), D-dimer, GDF-15 (Growth differentiation factor 15), Myoglobin, sP-Selectin, Serum Amyloid A will be measured at time 0 and 300 minutes after test meal intake | baseline, 8 and 9 weeks | 
| Change from baseline fasting plasma oxidative stress parameters: GSH, GSSG, Glutathion peroxidase/ reductase activity, MDA | GSH (glutathione), GSSG (glutathione disulfide), Glutathion peroxidase/ reductase activity will be measured at time 0 and MDA (malondialdehyde) will be measured at 0 and 300 minutes after test meal intake | baseline, 8 and 9 weeks | 
| Change from baseline body composition | Body composition will be measured by BodPod technique | baseline, 8 and 9 weeks | 
| Change from baseline plasma metabolites and hormone kinetics : glucose, insulin, triglycerides, non-esterified fatty acids | Plasma metabolites and hormone will be measured at time -30, 0, 15, 30, 45, 60, 90, 120, 180, 240, 300 minutes after test meal intake | baseline, 8 and 9 weeks | 
| Change from baseline fasting plasma lipids : total cholesterol , HDL cholesterol, LDL cholesterol, triglycerides, non-esterified fatty acids | fasting plasma lipids will be measured before test meal ingestion | baseline, 8 and 9 weeks | 
| Change from baseline resting energy expenditure | resting metabolic rate will be measured by indirect calorimetry | baseline, 8 and 9 weeks | 
| Change from baseline substrates oxidation | substrates oxidation will be measured by indirect calorimetry after test meal intake during five hours. | baseline, 8 and 9 weeks | 
| Change from baseline gut microbiota composition | gut microbiota composition will be measured by 16S RNA (ribonucleic acid) analysis | baseline, 8 weeks | 
| Change from baseline stool consistency | stool consistency will be measured by Bristol scale and every week during the interventional period | nine weeks | 
| Change from baseline stool frequency | stool frequency will be measured by questionnaire at baseline and every week during the interventional period | nine weeks | 
| Change from baseline tolerance gastro-intestinal symptoms like bloating ,abdominal rumbling ,flatulence ,abdominal pain, nausea, vomiting | Gastro intestinal symptoms will be collected by questionnaires and visual analogue scale (VAS) score (on a 90mm horizontal line; from no symptom (minimal) to serious symptom (maximum)) at baseline and every week during the interventional period | nine weeks | 
| Change from baseline diet intake | diet intake will be evaluated by a three days diet survey | baseline, 8 and 9 weeks | 
| Change from baseline fasting plasma zonulin | comparison of fasting plasma zonulin from baseline | baseline, 8 and 9 weeks | 
| Change from baseline polyphenols urinary concentrations | Comparison of polyphenols urinary concentrations from baseline | baseline, 8 weeks | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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fibers, inflammation, cardiometabolic risk, endotoxemia, polyphenols, oxidative stress, slow digestible starch, gut microbiota, nutritional challenge test