Towards a Food Ingredient Clinically Proven to Benefit Gut Health: Novel RG-I Variants

Study Overview
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Brief Summary
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The aim of this study is to determine, quantify and understand the potential prebiotic effects of RG-I variants via microbiota modulation. The anti-inflammatory potential effects of these variants will also be investigated.

Detailed Description
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The plant cell wall derived RG-I (from chicory or carrot) and maltodextrin (placebo) in capsuled form will be provided by the food company NutriLeads B.V (Wageningen, The Netherlands), which has run tests of safety of the products and warranties their food grade quality and safety. The administration of RG-I will be done via a human intervention study of parallel arms, randomized, placebo - controlled, double blinded design (proof of concept study). The dietary fibre from different RG-I sources will be tested for its prebiotic and immunomodulatory potential. Thus, the effects of these fibres on short chain fatty acid (SCFA) profile, microbiota composition, microbiota-associated metabolites and intestinal inflammatory markers will be investigated from fecal material obtained from the study participants. The dietary fibre from different RG-I sources will be tested for their immunomodulatory and lifestyle related effects. The effects of fibres on immune activation markers will be investigated from blood samples collected from the study participants.

Official Title
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Towards a Food Ingredient Clinically Proven to Benefit Gut Health: Novel RG-I Variants

Conditions
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Healthy

Intervention / Treatment
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* Dietary Supplement: Maltodextrin
* Dietary Supplement: Chicory RG-I
* Dietary Supplement: Carrot RG-I


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Signed consent prior to any study related procedures Age 18-70 years Willing to abstain from regular consumption of prebiotics/probiotics/synbiotics products or medication known to alter gastrointestinal functions at least 4 weeks prior to the study visits Body mass index (BMI) ≥ 18.5 and ≤ 30.0 kg m-2 Exclusion Criteria: Previous complicated gastrointestinal surgery Presence of gastrointestinal disorder or any disorder which the principal investigator considers to affect the results of the study Current diagnosis of psychiatric disease Current and past diagnosis inflammatory gastrointestinal disease (e.g. Inflammatory Bowel Disease) Systemic use of antibiotics or steroids medications in the last 3 months prior to study visits Frequent use of NSAID (Non-Steroidal Anti Inflammatory Drugs) the last 2 months prior to study visits Abuse of alcohol or drugs Frequent use of laxatives, anti-diarrheal, anti-cholinergic within last 3 months prior to study visits Pregnancy and breast-feeding Vegan dietary habits or consumption of dietary fibers ≥ 25 g per day according to the food frequency questionnaire Smoking or usage of snus within last 3 months prior to study visits No recent weight loss or gain 5% of their normal weight in the last month

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Placebo<br>Participants who will be randomized in the placebo group will receive maltodextrin (500mg/day). | Dietary Supplement: Maltodextrin<br>* During the feeding period (4 weeks) two capsules/ day will be administered to subjects randomized in this group containing placebo powder with a breakfast item on a daily basis.<br>|
| Experimental: Chicory RG-I<br>Participants who will be randomized in the placebo group will receive Chicory RG-I (500mg/day). | Dietary Supplement: Chicory RG-I<br>* During the feeding period (4 weeks) two capsules/ day will be administered to subjects randomized in this group containing chicory RG-I with a breakfast item on a daily basis.<br>|
| Experimental: Carrot RG-I<br>Participants who will be randomized in the placebo group will receive Carrot RG-I (500mg/day). | Dietary Supplement: Carrot RG-I<br>* During the feeding period (4 weeks) two capsules/ day will be administered to subjects randomized in this group containing carrot RG-I with a breakfast item on a daily basis.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to the effect on selected intestinal microbial populations. | Selected microbial populations will be quantified with quantitative Polymerase Chain Reaction (PCR). | The levels of the selected microbial populations will be measured weekly from baseline till the end of the interventional period.(4 weeks period) | 
| Change from baseline to the effect on the intestinal microbial populations. | Microbial populations will be quantified with 16SRNA sequencing. | The levels of the microbial populations will be measured weekly from baseline till the end of the interventional period.(4 weeks period) | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change from baseline to the effect on the intestinal microbial populations's metabolic products [i.e. Short-Chain Fatty Acids (SCFA)]. | SCFAs will be quantified with Gas chromatography. | SCFAs levels will be evaluated at baseline and at the end of the intervention. (4 weeks period) | 
| Change from baseline to the effect on immune system reinforcement. | Plasmacytoid dendritic cells activation will be evaluated with flow cytometry. | Immune system reinforcement will be evaluated at baseline and at the end of the intervention. (4 weeks period) | 
| Change from baseline to the effect on inflammation. | Inflammatory related markers will be quantified by ELISA techniques. | Inflammation will be evaluated at baseline and at the end of the intervention. (4 weeks period) | 
| Change from baseline to the effect on exhaled volatile organic compounds levels. | Exhaled volatile organic compounds levels will be evaluated with Thermal Desorption Gas chromatography. | Exhaled volatile organic compounds levels will be evaluated at baseline and at the end of the intervention. (4 weeks period) | 
| Change from baseline to the effect on fecal metabolomic fingerprinting. | Metabolomic fingerprinting will be evaluated by applying laser assisted Rapid Evaporative Ionisation Mass Spectrometry (LA-REIMS) method on biological material. | Metabolomic fingerprinting will be evaluated at baseline and at the end of the intervention. (4 weeks period) | 
| Gastrointestinal tolerance of the supplement. | Gastrointestinal health will be evaluated with the use of a 1-day questionnaire consisting of 13 items concerning satiety, abdominal pain, diarrhea, constipation and bloating.The intensity of each parameter will be assessed on a scale of 0-7, where '0' represents absence of symptoms and '7' severe symptoms. | Gastrointestinal symptoms will be evaluated at baseline and at the end of the intervention. (4 weeks period) | 
| Dietary habits prior to the initiation of the study. | Dietary habits will be evaluated with the use of food frequency questionnaire (FFQ). | Dietary habits will be measured at baseline prior to the initiation of the study as background information. | 
| Changes from baseline to the effect on physical activity levels. | Physical activity will be evaluated with the use of a validated questionnaire. IPAQ consists of 7 items questions concerning the duration and the intensity of physical activity so absolute numerical data will be obtained from it. | Physical activity will be evaluated at baseline and at the end of the intervention. (4 weeks period) | 
| Changes from baseline to the effect on quality of life. | Quality of life will be evaluated with the use of a validated questionnaire. EQ-5D-5L consists of 5 items concerning mobility, self-care, usual activities, pain/discomfort, anxiety/depression.The overall score from this questionnaire will be calculated by assigning a numerical value to each response level (i.e., 1 for no problems, 5 for extreme problems/unable to) and summing these values across the five items, resulting in a score from 5 (11,111, no problems on any dimension) to 25 (55,555, extreme problems on all dimensions). | Quality of life will be evaluated at baseline and at the end of the intervention. (4 weeks period) | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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prebiotic, short - chain fatty acids (SCFAs), Plasmacytoid dendritic cell markers (PDCs), gut microbiota, rhamnogalacturonan I, immune response