NATURE 3.1_New Approach for the Reduction of REnal Uremic Toxins (NATURE31)
Primary Purpose
Chronic Kidney Diseases, Healthy
Status
Completed
Phase
Not Applicable
Locations
Italy
Study Type
Interventional
Intervention
Symbiotic
Placebo
Sponsored by

About this trial
This is an interventional treatment trial for Chronic Kidney Diseases focused on measuring gut microbiota dysbiosis, uremic toxins, symbiotic
Eligibility Criteria
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
Sites / Locations
- AUO Policlinico Consorziale
Arms of the Study
Arm 1
Arm 2
Arm Type
Experimental
Other
Arm Label
CKD patients
Controls
Arm Description
CKD patients stage 3b-4 will follow a 2-months supplementation of either symbiotic or placebo
Healthy volunteers will follow a 2-months supplementation of either symbiotic or placebo
Outcomes
Primary Outcome Measures
Change of serum concentration of pCS
Change of p-cresyl sulfate (pCS) serum concentrations assessed by liquid chromatography/mass spectrometry
Secondary Outcome Measures
Change of serum concentration of IS
Change of indoxyl sulfate (IS) serum concentrations assessed by liquid chromatography/mass spectrometry
Change of serum concentration of D-lactate
Change of D-lactate serum concentration (uM)
Change of serum concentration of LPS
Change of lipopolysaccharide (LPS) serum concentration (EU/ml)
Change of percentage of sugar urinary recovery
Change of percentage (%) of urinary recovery of 4 sugars (lactulose, mannitol, sucrose and sucralose)
Change of serum concentration of inflammatory markers
Change of interleukin (IL)6, IL10, IL17, pentraxin3 (PTX3) serum concentrations (pg/ml) evaluated by ELISA
Change of serum concentration of NO
Change of nitric oxide (NO) serum concentration (uM) evaluated by spectrometry
Full Information
NCT ID
NCT03815786
First Posted
November 23, 2018
Last Updated
February 1, 2022
Sponsor
Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
Collaborators
University of Bari Aldo Moro
1. Study Identification
Unique Protocol Identification Number
NCT03815786
Brief Title
NATURE 3.1_New Approach for the Reduction of REnal Uremic Toxins
Acronym
NATURE31
Official Title
XUANRO4 - NATURE 3.1 - Nuovo Approccio Per la Riduzione Delle Tossine Uremiche Renali, REGIONE PUGLIA FSC 2007-2013 Ricerca. Intervento Cluster Tecnologici Regionali
Study Type
Interventional
2. Study Status
Record Verification Date
November 2018
Overall Recruitment Status
Completed
Study Start Date
May 24, 2017 (Actual)
Primary Completion Date
October 17, 2017 (Actual)
Study Completion Date
October 17, 2017 (Actual)
3. Sponsor/Collaborators
Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Azienda Ospedaliero-Universitaria Consorziale Policlinico di Bari
Collaborators
University of Bari Aldo Moro
4. Oversight
Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Data Monitoring Committee
No
5. Study Description
Brief Summary
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
6. Conditions and Keywords
Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Diseases, Healthy
Keywords
gut microbiota dysbiosis, uremic toxins, symbiotic
7. Study Design
Primary Purpose
Treatment
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
50 (Actual)
8. Arms, Groups, and Interventions
Arm Title
CKD patients
Arm Type
Experimental
Arm Description
CKD patients stage 3b-4 will follow a 2-months supplementation of either symbiotic or placebo
Arm Title
Controls
Arm Type
Other
Arm Description
Healthy volunteers will follow a 2-months supplementation of either symbiotic or placebo
Intervention Type
Dietary Supplement
Intervention Name(s)
Symbiotic
Intervention Description
2-months oral administration of the symbiotic supplement (2 bags/day) + 1 month washout
Intervention Type
Dietary Supplement
Intervention Name(s)
Placebo
Intervention Description
2-months oral administration of the placebo (2 bags/day) + 1 month washout
Primary Outcome Measure Information:
Title
Change of serum concentration of pCS
Description
Change of p-cresyl sulfate (pCS) serum concentrations assessed by liquid chromatography/mass spectrometry
Time Frame
3 months
Secondary Outcome Measure Information:
Title
Change of serum concentration of IS
Description
Change of indoxyl sulfate (IS) serum concentrations assessed by liquid chromatography/mass spectrometry
Time Frame
3 months
Title
Change of serum concentration of D-lactate
Description
Change of D-lactate serum concentration (uM)
Time Frame
3 months
Title
Change of serum concentration of LPS
Description
Change of lipopolysaccharide (LPS) serum concentration (EU/ml)
Time Frame
3 months
Title
Change of percentage of sugar urinary recovery
Description
Change of percentage (%) of urinary recovery of 4 sugars (lactulose, mannitol, sucrose and sucralose)
Time Frame
3 months
Title
Change of serum concentration of inflammatory markers
Description
Change of interleukin (IL)6, IL10, IL17, pentraxin3 (PTX3) serum concentrations (pg/ml) evaluated by ELISA
Time Frame
3 months
Title
Change of serum concentration of NO
Description
Change of nitric oxide (NO) serum concentration (uM) evaluated by spectrometry
Time Frame
3 months
Other Pre-specified Outcome Measures:
Title
Gut microbiota
Description
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.
Time Frame
3 months
Title
Change of GI symptoms
Description
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)
Time Frame
3 months
Title
Change of stool type
Description
Change of stool type evaluated by BRISTOL Stool Scale (range 1-7, lower and higher values representing worse outcome, middle values representing better outcome)
Time Frame
3 months
Title
Change of serum concentration of TMAO
Description
Change of trimethylamine-N-oxide (TMAO) serum concentrations assessed by liquid chromatography/mass spectrometry
Time Frame
3 months
10. Eligibility
Sex
All
Minimum Age & Unit of Time
30 Years
Maximum Age & Unit of Time
65 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Loreto Gesualdo, MD Full Prof
Organizational Affiliation
Nephrology, Dialysis and Transplantation Unit "Aldo Moro" University of Bari
Official's Role
Principal Investigator
Facility Information:
Facility Name
AUO Policlinico Consorziale
City
Bari
State/Province
BA
ZIP/Postal Code
70125
Country
Italy
12. IPD Sharing Statement
Plan to Share IPD
Undecided
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NATURE 3.1_New Approach for the Reduction of REnal Uremic Toxins
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