Impact of Intestinal Microbiota on Uremic Toxins Productions

CKD Clinical Trial

— GUTCOL  

Official title:

Assessment of the Production of Uremic Toxins by the Gut Microbiota of Patients With Chronic Kidney Disease: in Vitro Test

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04768309
• Other study ID #: 69HCL20_1078
• Status: Completed
• Phase: N/A
• Start date: June 4, 2021
• Est. completion date: July 13, 2021

Study information

• Verified date: September 2023
• Source: Hospices Civils de Lyon
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 20
• Est. completion date: July 13, 2021
• Est. primary completion date: July 13, 2021
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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)

Related Conditions & MeSH terms

• CKD
• Uremia

Intervention

Other:
• Ex vivo exploration of the effect of a probiotic over precursor indole production
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.

Locations

Country	Name	City	State
France	Lyon Sud University Hospital	Pierre-Bénite	Rhône

Sponsors (1)

Lead Sponsor	Collaborator
Hospices Civils de Lyon

Country where clinical trial is conducted

France, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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)	Indoles production will be measured 48 hours after instillation of fresh feces in the artificial intestine
Secondary	Uremic toxins production	Concentration of various uremic toxins in a human intestine simulator (p-cresyl sulfate, p-cresol, indole-3-acetic acid, etc.).	48 hours after instillation of fresh feces in the human intestine simulator
Secondary	Production of short-chain fatty acids (SCFA)	Concentration of short-chain fatty acids (SCFA) (acetate, propionate, butyrate, isobutyrate, isovalerate and isocaproate) human intestine simulator	48 hours after instillation of fresh feces in the human intestine simulator
Secondary	Intestinal permeability in a human intestine simulator	It will be measured by the electrical transepithelial resistance of the intestinal cells.	48 hours after instillation of fresh feces in the human intestine simulator
Secondary	Biochemical parameters	Concentration of ammonium and lactate in a human intestine simulator.	48 hours after instillation of fresh feces in the human intestine simulator
Secondary	Biochemical parameters	pH levels of the human intestine simulator.	48 hours after instillation of fresh feces in the human intestine simulator
Secondary	Biochemical parameters	Volume of gas production in a human intestine simulator.	48 hours after instillation of fresh feces in the human intestine simulator
Secondary	Intestinal microbiota composition	Study of the composition of the intestinal microbiota by 16s analysis	48 hours after instillation of fresh feces in the human intestine simulator