Clinical trial NCT04768309: Impact of Intestinal Microbiota on Uremic Toxins Productions
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
Overall status: COMPLETED
Phase: NA
Conditions: CKD
Uremia
Keywords: CKD
uremic toxin
probiotics
intestinal microbiota
artificial intestine
Lead sponsor: Hospices Civils de Lyon
Sponsor class: OTHER
First posted: 2021-02-24
Enrollment: 20
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NON_RANDOMIZED
Intervention model: PARALLEL
Primary purpose: OTHER

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.


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)

Primary outcomes:
measure: Production of precursor of one of major uremic toxins: indole
timeFrame: Indoles production will be measured 48 hours after instillation of fresh feces in the artificial intestine
Secondary outcomes:
measure: Uremic toxins production
timeFrame: 48 hours after instillation of fresh feces in the human intestine simulator
measure: Production of short-chain fatty acids (SCFA)
timeFrame: 48 hours after instillation of fresh feces in the human intestine simulator
measure: Intestinal permeability in a human intestine simulator
timeFrame: 48 hours after instillation of fresh feces in the human intestine simulator
measure: Biochemical parameters
timeFrame: 48 hours after instillation of fresh feces in the human intestine simulator
measure: Biochemical parameters
timeFrame: 48 hours after instillation of fresh feces in the human intestine simulator
measure: Biochemical parameters
timeFrame: 48 hours after instillation of fresh feces in the human intestine simulator
measure: Intestinal microbiota composition
timeFrame: 48 hours after instillation of fresh feces in the human intestine simulator
Other outcomes:
Locations:
city: Pierre-Bénite
country: France
facility: Lyon Sud University Hospital
state: Rhône
Study officials:
References: