NATURE 3.2_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 a combined approach based on the use of an innovative symbiotic and an innovative dialysis cartridge in patients on hemodialysis (HD). The symbiotic consists of a mixture of probiotics (Lactobacilli and Bifidobacteria), prebiotics (fructoligosaccharides and inulin) and natural antioxidants (a mix of quercetin, resveratrol and proanthocyanidins). The cartridge is composed of a divinylbenzene (DVB) adsorbing resine, expected to have high affinity to protein-bound uremic toxins pCS and IS, on the basis of its chemical structure. This combined approach will be aimed at achieving two main objectives: reduction of blood levels of microbial-derived uremic toxins, involved in cardiovascular complications reduction of inflammation markers and oxidative stress and reduction of intestinal permeability

Official Title
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XUANRO4 - NATURE 3.2 - Nuovo Approccio Per la Riduzione Delle Tossine Uremiche Renali, REGIONE PUGLIA - FSC 2007-2013 Ricerca. Intervento Cluster Tecnologici Regionali

Conditions
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Hemodialysis

Intervention / Treatment
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* Dietary Supplement: Symbiotic
* Dietary Supplement: Placebo
* Device: DVB cartridge


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: CKD patients on bicarbonate hemodialysis Aged between 30 to 65 BMI between 18.5 and 29.9 Omnivore diet Informed consent signed Exclusion Criteria: 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 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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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Factorial Assignment
Masking: Single


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Symbiotic<br>HD patients with 7 weeks symbiotic administration + 1 week overlapping with the 3 dialytic sessions with the DVB cartridge | Dietary Supplement: Symbiotic<br>* HD patients follow a 8-weeks oral administration of the symbiotic supplement (2 bags/day)<br>Device: DVB cartridge<br>* On the last week of the symbiotic/placebo period, patients undergo 3 dialytic sessions with the DVB cartridge<br>|
| Placebo Comparator: Placebo<br>HD patients with 7 weeks placebo administration + 1 week overlapping with the 3 dialytic sessions with the DVB cartridge | Dietary Supplement: Placebo<br>* HD patients follow a 8-weeks oral administration of the placebo (2 bags/day)<br>Device: DVB cartridge<br>* On the last week of the symbiotic/placebo period, patients undergo 3 dialytic sessions with the DVB cartridge<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 | 8 weeks | 

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 | 8 weeks | 
| Change of serum concentration of D-lactate | Change of D-lactate serum concentration (uM) | 8 weeks | 
| Change of serum concentration of LPS | Change of lipopolysaccharide (LPS) serum concentration (EU/ml) | 8 weeks | 
| Change of serum concentration of inflammatory markers | Change of interleukin (IL)IL10, IL17, pentraxin3 (PTX3) serum concentrations (pg/ml) evaluated by ELISA | 8 weeks | 
| Change of serum concentration of NO | Change of nitric oxide (NO) serum concentration (uM) evaluated by spectrometry | 8 weeks | 

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