NATURE 3.2_New Approach for the Reduction of REnal Uremic Toxins (NATURE32)

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

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:

1. reduction of blood levels of microbial-derived uremic toxins, involved in cardiovascular complications
2. reduction of inflammation markers and oxidative stress and reduction of intestinal permeability

Study Overview

• Status: Completed
• Conditions: Hemodialysis
• Intervention / Treatment: Dietary supplement: Symbiotic; Device: DVB cartridge; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 16
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • Bari, Italy, 70124
    • AOUConsorziale Policlinico Di Bari

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Factorial Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

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

What is the study measuring?

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

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Gut microbiota	Change of the relative abundance (%) of Operational Taxonomic Units (OTUs) of Firmicutes, Bacteroidetes,Proteobacteria, Verrucomicrobia, Actinobacteria, Synergistetes, Cyanobacteria, Euryarchaeota, Chloroflexi, Nitrospirae, Tenericutes, Fusobacteria, Thermotogae, Acidobacteria evaluated by fecal bacterial DNA genome sequencing.	8 weeks
Change of GI symptoms	Change of gastrointestinal symptoms evaluated by Gastrointestinal Symptoms Rating Scale (GSRS) questionnaire (15 items scored 1-7 each, 1 representing the best and 7 the worse outcome for each item)	8 weeks
Change of stool type	Change of stool type evaluated by BRISTOL Stool Scale (range 1-7, lower and higher values representing worse outcome, middle values representing better outcome)	8 weeks
Change of serum concentration of TMAO	Change of trimethylamine-N-oxide (TMAO) serum concentrations assessed by liquid chromatography/mass spectrometry	8 weeks

Collaborators and Investigators

• Sponsor: Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
• Collaborators: University of Bari Aldo Moro

Study record dates

Study Major Dates

• Study Start (Actual): May 17, 2017
• Primary Completion (Actual): October 27, 2017
• Study Completion (Actual): October 27, 2017

Study Registration Dates

• First Submitted: May 9, 2019
• First Submitted That Met QC Criteria: May 9, 2019
• First Posted (Actual): May 10, 2019

Study Record Updates

• Last Update Posted (Actual): May 10, 2019
• Last Update Submitted That Met QC Criteria: May 9, 2019
• Last Verified: January 1, 2019

More Information

Terms related to this study

• Keywords: uremic toxins; symbiotic; gut microbiota dysbiosis; divinylbenzene cartridge
• Other Study ID Numbers: XUANRO4-NATURE 3.2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No