Try the modernized ClinicalTrials.gov beta website. Learn more about the modernization effort.
Working…
ClinicalTrials.gov
ClinicalTrials.gov Menu

Impact of Intestinal Microbiota on Uremic Toxins Productions (GUTCOL)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04768309
Recruitment Status : Not yet recruiting
First Posted : February 24, 2021
Last Update Posted : February 24, 2021
Sponsor:
Information provided by (Responsible Party):
Hospices Civils de Lyon

Study Description
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
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.

Condition or disease Intervention/treatment Phase
CKD Uremia Other: Ex vivo exploration of the effect of a probiotic over precursor indole production Not Applicable

Study Design
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Layout table for study information
Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 20 participants
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)
Primary Purpose: Other
Official Title: Assessment of the Production of Uremic Toxins by the Gut Microbiota of Patients With Chronic Kidney Disease: in Vitro Test
Estimated Study Start Date : February 2021
Estimated Primary Completion Date : July 2021
Estimated Study Completion Date : February 2022
Arms and Interventions
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Arm Intervention/treatment
Experimental: CKD group
CKD adult patients stage 4-5 Without diabetes BMI between 18 and 30 kg/m2
 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.
Healthy volunteers group
Adult without chronic treatment, without renal dysfunction
 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.


Outcome Measures
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Primary Outcome Measures :
  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 Outcome Measures :
  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


Eligibility Criteria
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the contacts provided below. For general information, Learn About Clinical Studies.


Layout table for eligibility information
Ages Eligible for Study:   18 Years to 80 Years   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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)
Contacts and Locations
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04768309


Contacts
Layout table for location contacts
Contact: Laetitia KOPPE, MD, PhD +33 4 72 67 87 15 laetitia.koppe@chu-lyon.fr
Contact: Cécile BARNEL +33 4 78 86 37 12 cecile.barne@chu-lyon.fr

Locations
Layout table for location information
France
Lyon Sud University Hospital
Pierre-Bénite, Rhône, France, 69310
Contact: Laetitia KOPPE, MD, PhD    +33 4 72 67 87 15    laetitia.koppe@chu-lyon.fr   
Sponsors and Collaborators
Hospices Civils de Lyon
More Information
Go to 
Top of Page Study Description Study Design Arms and Interventions Outcome Measures Eligibility Criteria Contacts and Locations More Information
Layout table for additonal information
Responsible Party: Hospices Civils de Lyon
ClinicalTrials.gov Identifier: NCT04768309    
Other Study ID Numbers: 69HCL20_1078
First Posted: February 24, 2021    Key Record Dates
Last Update Posted: February 24, 2021
Last Verified: February 2021

Layout table for additional information
Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Hospices Civils de Lyon:
CKD
uremic toxin
probiotics
intestinal microbiota
artificial intestine
Additional relevant MeSH terms:
Layout table for MeSH terms
Uremia
Kidney Diseases
Urologic Diseases