NATURE 3.1_New Approach for the Reduction of REnal Uremic Toxins (NATURE31)

XUANRO4 - NATURE 3.1 - 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 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:

1. Reduction of the serum levels of microbiota-derived uremic toxins, involved in a variety of cardiovascular complications in CKD
2. Reduction of intestinal permeability, inflammatory markers and oxidative stress

Study Overview

• Status: Completed
• Conditions: Healthy; Chronic Kidney Diseases
• Intervention / Treatment: Dietary supplement: Symbiotic; Dietary supplement: Placebo

• Study Type: Interventional
• Enrollment (Actual): 50
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Italy
  • BA
    • Bari, BA, Italy, 70125
      • AUO Policlinico Consorziale

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 30 years to 65 years (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

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

Number of Arms

2

Arms and Interventions

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

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	3 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of serum concentration of D-lactate	Change of D-lactate serum concentration (uM)	3 months
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 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

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.	3 months
Change of GI symptoms	Change of gastrointestinal symptoms evaluated by Gastrointestinal Symptoms Rating Scale (GSRS) questionnaire (15 items scored 0-3 each, 0 representing the best and 3 the worse outcome for each item)	3 months
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)	3 months
Change of serum concentration of TMAO	Change of trimethylamine-N-oxide (TMAO) serum concentrations assessed by liquid chromatography/mass spectrometry	3 months

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 24, 2017
• Primary Completion (Actual): October 17, 2017
• Study Completion (Actual): October 17, 2017

Study Registration Dates

• First Submitted: November 23, 2018
• First Submitted That Met QC Criteria: January 21, 2019
• First Posted (Actual): January 24, 2019

Study Record Updates

• Last Update Posted (Actual): February 15, 2022
• Last Update Submitted That Met QC Criteria: February 1, 2022
• Last Verified: November 1, 2018

More Information

Terms related to this study

• Keywords: uremic toxins; symbiotic; gut microbiota dysbiosis
• Additional Relevant MeSH Terms: Urologic Diseases; Renal Insufficiency; Kidney Diseases; Renal Insufficiency, Chronic
• Other Study ID Numbers: XUANRO4-NATURE 3.1

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