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Impact of Dapagliflozin on Intestinal Microbiota Composition and on the Metabolites Derived From the Intestinal Microbiota in Non-diabetic Chronic Renal Failure Patients (DAPA-GUT)

Primary Purpose

Chronic Kidney Diseases

Status
Recruiting
Phase
Not Applicable
Locations
France
Study Type
Interventional
Intervention
impact of Dapagliflozin on Intestinal Microbiota on chronic renal failure patients
Sponsored by
Hospices Civils de Lyon
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional diagnostic trial for Chronic Kidney Diseases focused on measuring CKD, gliflozine, gut microbiota, metabolomic, uremic toxin

Eligibility Criteria

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

Inclusion Criteria: Age between 18 and 80 years old Non-diabetic patient Patient with a medical indication for the introduction of dapagliflozin according to the Marketing Authorization and as part of routine care, ie: An estimated GFR between 25 and 60 mL/min/1.73m2 according to the CKD EPI formula. A urinary albumin/creatinine ratio > 200mg/g and < 5000 mg/g Be treated with the maximum tolerated dose of renin-angiotensin system inhibitors for at least 4 weeks. BMI between 18 and 30 kg/m2 Patient not taking dapagliflozin (or any other treatment containing iSGLT2 or iSGLT1) Very regular bowel movements between 24 and 48 hours Patient following the dietary recommendations recommended during CKD (a sodium intake targeting 6g NaCl/day +/-20% and a protein intake of 0.6g/kg/d +/-20%) Affiliation to social security Exclusion Criteria: Taking drugs can interfere with the intestinal microbiota (prebiotics, probiotics, postbiotics, antibiotics) in the last 6 weeks Patient using high dose laxatives (more than 2 per day, for more than 3 months) Patient with a foreseeable transplant or dialysis project within the next 6 months. Patient with a colectomy, a resection of the small intestine or a cholecystectomy Patient with a progressive and unstabilized inflammatory, infectious, cardiovascular or neoplastic disease Inability to understand the nature, follow-up and possible consequences of the study. Patient in exclusion period from previous study or already participating in a clinical research protocol having an impact on the endpoints of the study Patient under guardianship or in safeguard of justice Pregnant, parturient or breastfeeding women

Sites / Locations

  • Nephrology department, Hôpital Lyon Sud, Hospices Civils de LyonRecruiting

Arms of the Study

Arm 1

Arm Type

Other

Arm Label

impact of Dapagliflozin on Intestinal Microbiota on chronic renal failure patients

Arm Description

Addition of 3 blood tubes of 5mL during the collection for the treatment Collection of fresh urine (7 mL) Collection of stools by the participant at his home Collection of fresh stools for patients participating in the ancillary study Constitution of a biocollection (blood, urine and stool) Food collection for 3 days with no impact on patient follow-up Stool appearance sheet to be completed by the patient at each collection

Outcomes

Primary Outcome Measures

Alpha diversity and beta diversity size of the intestinal microbiota after 12 weeks of daily treatment with dapagliflozin compared to alfa and beta diversity size before initiation of treatment.
The analysis of the microbiota by 16s sequencing of bacterial DNA will be carried out on the GenEPII platform located at the Croix Rousse hospital, Hospices Civils de Lyon (Pr Sophie JARRAUD).

Secondary Outcome Measures

Full Information

First Posted
July 20, 2023
Last Updated
October 2, 2023
Sponsor
Hospices Civils de Lyon
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1. Study Identification

Unique Protocol Identification Number
NCT05965440
Brief Title
Impact of Dapagliflozin on Intestinal Microbiota Composition and on the Metabolites Derived From the Intestinal Microbiota in Non-diabetic Chronic Renal Failure Patients
Acronym
DAPA-GUT
Official Title
Impact of Dapagliflozin on Intestinal Microbiota Composition and on the Metabolites Derived From the Intestinal Microbiota in Non-diabetic Chronic Renal Failure Patients
Study Type
Interventional

2. Study Status

Record Verification Date
October 2023
Overall Recruitment Status
Recruiting
Study Start Date
October 2, 2023 (Actual)
Primary Completion Date
December 15, 2024 (Anticipated)
Study Completion Date
December 15, 2024 (Anticipated)

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
Data Monitoring Committee
No

5. Study Description

Brief Summary
Chronic kidney disease (CKD) is a common disease affecting 10-12% of the adult population and characterize with high-risk cardiovascular morbidity and mortality with progression of CKD. Treatment with sodium-glucose cotransporter 2 inhibitors (iSGLT2) not only improves hyperglycemia and type 2 diabetes (T2D) but also results in body-weight loss, a reduction in blood pressure, and a decrease of cardiovascular events and progression of renal failure in both diabetes and non-diabetes patients.(Heerspink et al. 2020) Therefore, dapagliflozin is now associated with the inhibitors of the renin-angiotensin system to reduce kidney events. However, the mechanisms underlying the effects of dapagliflozin on the renal function remain unclear. When renal failure occurs, it impairs the removal of several metabolites called uremic retention solutes. If these retention solutes exhibit deleterious interferences with biochemical/physiological functions, they are referred to as uremic toxins as they can contribute to the manifestations of the uremic syndrome and are associated with a high cardiovascular morbidity and mortality and with progression of CKD. Many of the uremic toxins are not produced by the body itself but rather derived from gut microbiota metabolism such as the well-known trimethylamine-N-oxide (TMAO),p-cresyl sulfate (PCS), phenyl sulfate (PS), indoxyl sulfate (IS), and indole-3-acetic acid (IAA).The gut microbiota composition in a uremic context has been the subject of an increasing number of publications and majority of them confirm a decrease of gut microbiota richness and deep modifications.Recently, an animal study suggested that dapagliflozin, subtly improve the composition of the gut microbiota in mice with T2D and another preliminary clinical study didn't observe a modification in the fecal microbiome after dapagliflozin initiation.But in other study, empagliflozin significantly reshaped the gut microbiota after 1 month of treatment in T2D patients and be associated with shifts in plasma metabolites. Similarly, canagliflozin reduces plasma uremic toxins in a CKD mice model.However, it remains unknown whether treatment with dapagliflozin alters the gut microbiota in CKD patients without T2D; furthermore, the relationship between the gut microbiota, uremic toxins production and CKD-related beneficial effects of dapagliflozin remains elusive. Herein, the investigator will investigate the clinical benefits of dapagliflozin and possible associations between its renal function benefits and alterations in plasmatic gut microbiota-derived metabolites and the gut microbiota composition in non-T2D CKD patients. To this end, the investigator will conduct an observational clinical trial in non-T2D CKD patients with the primary aim of investigating dapagliflozin-induced compositional changes of intestinal gut microbiota.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Chronic Kidney Diseases
Keywords
CKD, gliflozine, gut microbiota, metabolomic, uremic toxin

7. Study Design

Primary Purpose
Diagnostic
Study Phase
Not Applicable
Interventional Study Model
Single Group Assignment
Masking
None (Open Label)
Allocation
N/A
Enrollment
50 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
impact of Dapagliflozin on Intestinal Microbiota on chronic renal failure patients
Arm Type
Other
Arm Description
Addition of 3 blood tubes of 5mL during the collection for the treatment Collection of fresh urine (7 mL) Collection of stools by the participant at his home Collection of fresh stools for patients participating in the ancillary study Constitution of a biocollection (blood, urine and stool) Food collection for 3 days with no impact on patient follow-up Stool appearance sheet to be completed by the patient at each collection
Intervention Type
Drug
Intervention Name(s)
impact of Dapagliflozin on Intestinal Microbiota on chronic renal failure patients
Intervention Description
Analysis of microbiota
Primary Outcome Measure Information:
Title
Alpha diversity and beta diversity size of the intestinal microbiota after 12 weeks of daily treatment with dapagliflozin compared to alfa and beta diversity size before initiation of treatment.
Description
The analysis of the microbiota by 16s sequencing of bacterial DNA will be carried out on the GenEPII platform located at the Croix Rousse hospital, Hospices Civils de Lyon (Pr Sophie JARRAUD).
Time Frame
Before and 12 weeks after initiation of treatment with dapagliflozin

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 patient Patient with a medical indication for the introduction of dapagliflozin according to the Marketing Authorization and as part of routine care, ie: An estimated GFR between 25 and 60 mL/min/1.73m2 according to the CKD EPI formula. A urinary albumin/creatinine ratio > 200mg/g and < 5000 mg/g Be treated with the maximum tolerated dose of renin-angiotensin system inhibitors for at least 4 weeks. BMI between 18 and 30 kg/m2 Patient not taking dapagliflozin (or any other treatment containing iSGLT2 or iSGLT1) Very regular bowel movements between 24 and 48 hours Patient following the dietary recommendations recommended during CKD (a sodium intake targeting 6g NaCl/day +/-20% and a protein intake of 0.6g/kg/d +/-20%) Affiliation to social security Exclusion Criteria: Taking drugs can interfere with the intestinal microbiota (prebiotics, probiotics, postbiotics, antibiotics) in the last 6 weeks Patient using high dose laxatives (more than 2 per day, for more than 3 months) Patient with a foreseeable transplant or dialysis project within the next 6 months. Patient with a colectomy, a resection of the small intestine or a cholecystectomy Patient with a progressive and unstabilized inflammatory, infectious, cardiovascular or neoplastic disease Inability to understand the nature, follow-up and possible consequences of the study. Patient in exclusion period from previous study or already participating in a clinical research protocol having an impact on the endpoints of the study Patient under guardianship or in safeguard of justice Pregnant, parturient or breastfeeding women
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Laetitia KOPPE, M.D., Ph. D
Phone
+33 4 72 67 87 15
Email
laetitia.koppe@chu-lyon.fr
First Name & Middle Initial & Last Name or Official Title & Degree
Cécile BARNEL
Phone
+33 4 78 86 37 12
Email
cecile.barnel@chu-lyon.fr
Facility Information:
Facility Name
Nephrology department, Hôpital Lyon Sud, Hospices Civils de Lyon
City
Lyon
Country
France
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Laetitia KOPPE,, M.D., Ph. D

12. IPD Sharing Statement

Learn more about this trial

Impact of Dapagliflozin on Intestinal Microbiota Composition and on the Metabolites Derived From the Intestinal Microbiota in Non-diabetic Chronic Renal Failure Patients

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