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Completed

NCT Number: NCT04768309

Impact of Intestinal Microbiota on Uremic Toxins Productions

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.

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Key information

Age range

18 year–80 year

Sex eligibility

All sexes

Study type

Interventional

Phase

Not applicable

Primary location

Lyon Sud University Hospital

Pierre-Bénite, Rhône, 69310, France

Who can participate

Healthy volunteers accepted: Yes

Only the study team can determine whether someone qualifies for participation.

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)

Treatment and study plan

Ex vivo exploration of the effect of a probiotic over precursor indole production

Other

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 outcomes

  1. Production of precursor of one of major uremic toxins: indole

    Time frame: Indoles production will be measured 48 hours after instillation of fresh feces in the artificial intestine

    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 outcomes

  1. Uremic toxins production

    Time frame: 48 hours after instillation of fresh feces in the human intestine simulator

    Concentration of various uremic toxins in a human intestine simulator (p-cresyl sulfate, p-cresol, indole-3-acetic acid, etc.).

  2. Production of short-chain fatty acids (SCFA)

    Time frame: 48 hours after instillation of fresh feces in the human intestine simulator

    Concentration of short-chain fatty acids (SCFA) (acetate, propionate, butyrate, isobutyrate, isovalerate and isocaproate) human intestine simulator

  3. Intestinal permeability in a human intestine simulator

    Time frame: 48 hours after instillation of fresh feces in the human intestine simulator

    It will be measured by the electrical transepithelial resistance of the intestinal cells.

  4. Biochemical parameters

    Time frame: 48 hours after instillation of fresh feces in the human intestine simulator

    Concentration of ammonium and lactate in a human intestine simulator.

  5. Biochemical parameters

    Time frame: 48 hours after instillation of fresh feces in the human intestine simulator

    pH levels of the human intestine simulator.

  6. Biochemical parameters

    Time frame: 48 hours after instillation of fresh feces in the human intestine simulator

    Volume of gas production in a human intestine simulator.

  7. Intestinal microbiota composition

    Time frame: 48 hours after instillation of fresh feces in the human intestine simulator

    Study of the composition of the intestinal microbiota by 16s analysis

Sponsors and collaborators

Lead sponsor

Hospices Civils de Lyon

Other

Registry information

Official study title

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

Acronym: GUTCOL

Important dates

Study start
2021
Primary completion
2021
Study completion
2021
First posted
Feb 24, 2021
Registry last updated
Dec 19, 2025

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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