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Impact of Intestinal Microbiota on Uremic Toxins Productions (GUTCOL)

Primary Purpose

CKD, Uremia

Status
Completed
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
Ex vivo exploration of the effect of a probiotic over precursor indole production
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for CKD focused on measuring CKD, uremic toxin, probiotics, intestinal microbiota, artificial intestine

Eligibility Criteria

18 Years - 80 Years (Adult, Older Adult)All SexesAccepts Healthy Volunteers

Inclusion Criteria:

  • Age between 18 and 80 years old
  • Non diabetic (fasting blood glucose <1.26 g / L, or lack of insulin or oral antidiabetic treatment)
  • BMI between 18 and 30 kg / m²
  • Patient with CKD stage 4-5 ( eDFG < 30 ml/min/1.73m2 CKD-EPI)
  • Not dialyzed
  • No history of kidney transplant
  • Patient followed in the nephrology department of Pr FOUQUE at the Lyon Sud hospital center

Exclusion Criteria:

  • Active inflammatory, infectious, cardiovascular or neoplastic disease
  • Colectomy, resection of the small intestine or cholecystectomy
  • Patient having received antibiotics, prebiotics, probiotics in the last 3 months.
  • Patient using laxatives (more than 2 doses per day for the last 3 months)
  • Known renal pathology or known urologic malformation (healthy volunteer only)

Sites / Locations

  • Lyon Sud University Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Other

Arm Label

CKD group

Healthy volunteers group

Arm Description

CKD adult patients stage 4-5 Without diabetes BMI between 18 and 30 kg/m2

Adult without chronic treatment, without renal dysfunction

Outcomes

Primary Outcome Measures

Production of precursor of one of major uremic toxins: indole
The main endpoint is the concentration of the precursor of indoxyl sulfate (indole) in the lumen of the artificial intestine with a microbiota of a patient with CKD compared to the concentration of indol in the lumen of artificial intestine with a microbiota from a patient with CKD and supplemented with a probiotic (supplied by Nestlé)

Secondary Outcome Measures

Uremic toxins production
Concentration of various uremic toxins in a human intestine simulator (p-cresyl sulfate, p-cresol, indole-3-acetic acid, etc.).
Production of short-chain fatty acids (SCFA)
Concentration of short-chain fatty acids (SCFA) (acetate, propionate, butyrate, isobutyrate, isovalerate and isocaproate) human intestine simulator
Intestinal permeability in a human intestine simulator
It will be measured by the electrical transepithelial resistance of the intestinal cells.
Biochemical parameters
Concentration of ammonium and lactate in a human intestine simulator.
Biochemical parameters
pH levels of the human intestine simulator.
Biochemical parameters
Volume of gas production in a human intestine simulator.
Intestinal microbiota composition
Study of the composition of the intestinal microbiota by 16s analysis

Full Information

First Posted
February 12, 2021
Last Updated
September 26, 2023
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT04768309
Brief Title
Impact of Intestinal Microbiota on Uremic Toxins Productions
Acronym
GUTCOL
Official Title
Assessment of the Production of Uremic Toxins by the Gut Microbiota of Patients With Chronic Kidney Disease: in Vitro Test
Study Type
Interventional

2. Study Status

Record Verification Date
September 2023
Overall Recruitment Status
Completed
Study Start Date
June 4, 2021 (Actual)
Primary Completion Date
July 13, 2021 (Actual)
Study Completion Date
July 13, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Hospices Civils de Lyon

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No

5. Study Description

Brief Summary
Chronic renal failure (CKD) affects 3 million people in France and is characterized by the accumulation of uremic toxins (UTs) such as p-cresyl sulfate (PCS) and indoxyl sulfate (IS) which participate in cardiovascular complications and disturbance of the carbohydrate metabolism associated with CKD. These UTs are not eliminated by dialysis due to their high affinity for albumin and alternative strategies to dialysis must be developed to decrease the production of TUs in patients not yet in dialysis. The dysregulation of the intestinal microbiota observed during CKD increases the generation of UTs in the intestine, by the transformation of amino acids derived from proteins (such as tyrosine and tryptophan transformed respectively into PCS and, IS). Thus, modulation of the intestinal microbiota seems to be an attractive target for reducing the production of UTs and the comorbidities associated with CKD. Some studies have demonstrated the potential interest of probiotics in lowering the plasma concentration of UTs, but the effects remain unclear. In order to test the interest of probiotics during CKD, the investigators have, in collaboration with the Nestlé laboratory and the ProDigest platform, the possibility of testing probiotics using a human intestine simulator before the investigation of experimental and human models. For this the investigators would need a collection of fresh stools. The fresh stools will be instilled in artificial intestine to test the efficacy of selected probiotics on UTs production.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
CKD, Uremia
Keywords
CKD, uremic toxin, probiotics, intestinal microbiota, artificial intestine

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
20 (Actual)

8. Arms, Groups, and Interventions

Arm Title
CKD group
Arm Type
Experimental
Arm Description
CKD adult patients stage 4-5 Without diabetes BMI between 18 and 30 kg/m2
Arm Title
Healthy volunteers group
Arm Type
Other
Arm Description
Adult without chronic treatment, without renal dysfunction
Intervention Type
Other
Intervention Name(s)
Ex vivo exploration of the effect of a probiotic over precursor indole production
Intervention Description
Fresh feces in chronic kidney patients and healthy volunteers will be collected. The feces will be instilled in artificial intestine with and without selected probiotics and production of uremic toxins will be measured.
Primary Outcome Measure Information:
Title
Production of precursor of one of major uremic toxins: indole
Description
The main endpoint is the concentration of the precursor of indoxyl sulfate (indole) in the lumen of the artificial intestine with a microbiota of a patient with CKD compared to the concentration of indol in the lumen of artificial intestine with a microbiota from a patient with CKD and supplemented with a probiotic (supplied by Nestlé)
Time Frame
Indoles production will be measured 48 hours after instillation of fresh feces in the artificial intestine
Secondary Outcome Measure Information:
Title
Uremic toxins production
Description
Concentration of various uremic toxins in a human intestine simulator (p-cresyl sulfate, p-cresol, indole-3-acetic acid, etc.).
Time Frame
48 hours after instillation of fresh feces in the human intestine simulator
Title
Production of short-chain fatty acids (SCFA)
Description
Concentration of short-chain fatty acids (SCFA) (acetate, propionate, butyrate, isobutyrate, isovalerate and isocaproate) human intestine simulator
Time Frame
48 hours after instillation of fresh feces in the human intestine simulator
Title
Intestinal permeability in a human intestine simulator
Description
It will be measured by the electrical transepithelial resistance of the intestinal cells.
Time Frame
48 hours after instillation of fresh feces in the human intestine simulator
Title
Biochemical parameters
Description
Concentration of ammonium and lactate in a human intestine simulator.
Time Frame
48 hours after instillation of fresh feces in the human intestine simulator
Title
Biochemical parameters
Description
pH levels of the human intestine simulator.
Time Frame
48 hours after instillation of fresh feces in the human intestine simulator
Title
Biochemical parameters
Description
Volume of gas production in a human intestine simulator.
Time Frame
48 hours after instillation of fresh feces in the human intestine simulator
Title
Intestinal microbiota composition
Description
Study of the composition of the intestinal microbiota by 16s analysis
Time Frame
48 hours after instillation of fresh feces in the human intestine simulator

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
80 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Inclusion Criteria: Age between 18 and 80 years old Non diabetic (fasting blood glucose <1.26 g / L, or lack of insulin or oral antidiabetic treatment) BMI between 18 and 30 kg / m² Patient with CKD stage 4-5 ( eDFG < 30 ml/min/1.73m2 CKD-EPI) Not dialyzed No history of kidney transplant Patient followed in the nephrology department of Pr FOUQUE at the Lyon Sud hospital center Exclusion Criteria: Active inflammatory, infectious, cardiovascular or neoplastic disease Colectomy, resection of the small intestine or cholecystectomy Patient having received antibiotics, prebiotics, probiotics in the last 3 months. Patient using laxatives (more than 2 doses per day for the last 3 months) Known renal pathology or known urologic malformation (healthy volunteer only)
Facility Information:
Facility Name
Lyon Sud University Hospital
City
Pierre-Bénite
State/Province
Rhône
ZIP/Postal Code
69310
Country
France

12. IPD Sharing Statement

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