NATURE 3.1_New Approach for the Reduction of REnal Uremic Toxins

Study Overview
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Brief Summary
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The objective of the pilot study is to validate the clinical use of an innovative symbiotic in patients with chronic kidney disease (CKD) stage 3b-4 and in healthy subjects. The study aims at evaluating the effects of a symbiotic, consisting of a mixture of probiotics (Lactobacilli and Bifidobacteria), prebiotics (fructooligosaccharides and inulin) and natural antioxidants (a mix of quercetin, resveratrol and proanthocyanidins), by achieving two objectives: Reduction of the serum levels of microbiota-derived uremic toxins, involved in a variety of cardiovascular complications in CKD Reduction of intestinal permeability, inflammatory markers and oxidative stress

Official Title
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XUANRO4 - NATURE 3.1 - Nuovo Approccio Per la Riduzione Delle Tossine Uremiche Renali, REGIONE PUGLIA FSC 2007-2013 Ricerca. Intervento Cluster Tecnologici Regionali

Conditions
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Chronic Kidney Diseases, Healthy

Intervention / Treatment
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* Dietary Supplement: Symbiotic
* Dietary Supplement: Placebo


Participation Criteria
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Eligibility Criteria
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CKD patients Inclusion Criteria: CKD patients stage 3b-4 not on dialysis Aged between 30 to 65 BMI between 18.5 and 29.9 Controlled diet Informed consent signed Exclusion Criteria: Type 2 diabetes mellitus Use of antibiotics or probiotics up to 30 days prior to recruitment Chronic gastrointestinal disorders Systemic inflammatory diseases Suspicion or clinical diagnosis of malignancy Chronic liver disease Treatment with corticosteroids or immunosuppressive drugs Previous acute cardiovascular diseases (myocardial infarction, stroke) Psychiatric conditions reducing the compliance to treatment protocols Healthy volunteers Inclusion Criteria: Healthy subjects Aged between 35 to 60 BMI between 18.5 and 29.9 Medium score of adherence to Mediterranean Diet (PREDIMED score between 6 and 9) Informed consent signed Exclusion Criteria: Type 2 diabetes mellitus Use of antibiotics or probiotics up to 30 days prior to recruitment Chronic gastrointestinal disorders Systemic inflammatory diseases Suspicion or clinical diagnosis of malignancy Chronic liver disease Treatment with corticosteroids or immunosuppressive drugs Previous acute cardiovascular diseases (myocardial infarction, stroke) Psychiatric conditions reducing the compliance to treatment protocols

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: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: CKD patients<br>CKD patients stage 3b-4 will follow a 2-months supplementation of either symbiotic or placebo | Dietary Supplement: Symbiotic<br>* 2-months oral administration of the symbiotic supplement (2 bags/day) + 1 month washout<br>Dietary Supplement: Placebo<br>* 2-months oral administration of the placebo (2 bags/day) + 1 month washout<br>|
| Other: Controls<br>Healthy volunteers will follow a 2-months supplementation of either symbiotic or placebo | Dietary Supplement: Symbiotic<br>* 2-months oral administration of the symbiotic supplement (2 bags/day) + 1 month washout<br>Dietary Supplement: Placebo<br>* 2-months oral administration of the placebo (2 bags/day) + 1 month washout<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of serum concentration of pCS | Change of p-cresyl sulfate (pCS) serum concentrations assessed by liquid chromatography/mass spectrometry | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change of serum concentration of IS | Change of indoxyl sulfate (IS) serum concentrations assessed by liquid chromatography/mass spectrometry | 3 months | 
| Change of serum concentration of D-lactate | Change of D-lactate serum concentration (uM) | 3 months | 
| Change of serum concentration of LPS | Change of lipopolysaccharide (LPS) serum concentration (EU/ml) | 3 months | 
| Change of percentage of sugar urinary recovery | Change of percentage (%) of urinary recovery of 4 sugars (lactulose, mannitol, sucrose and sucralose) | 3 months | 
| Change of serum concentration of inflammatory markers | Change of interleukin (IL)6, IL10, IL17, pentraxin3 (PTX3) serum concentrations (pg/ml) evaluated by ELISA | 3 months | 
| Change of serum concentration of NO | Change of nitric oxide (NO) serum concentration (uM) evaluated by spectrometry | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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gut microbiota dysbiosis, uremic toxins, symbiotic