Ignite Creation Date:
2024-05-06 @ 7:18 PM
Last Modification Date:
2024-10-26 @ 3:04 PM
Study NCT ID:
NCT05965440
Status:
RECRUITING
Last Update Posted:
2023-11-29
First Post:
2023-07-20
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
Sponsor:
Hospices Civils de Lyon
Organization:
Hospices Civils de Lyon
Study Overview
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
Status:
RECRUITING
Status Verified Date:
2023-11
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
DAPA-GUT
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 patientsHeerspink 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 biochemicalphysiological 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 TMAOp-cresyl sulfate PCS phenyl sulfate PS indoxyl sulfate IS and indole-3-acetic acid IAAThe 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 modificationsRecently an animal study suggested that dapagliflozin subtly improve the composition of the gut microbiota in mice with T2D and another preliminary clinical study didnt observe a modification in the fecal microbiome after dapagliflozin initiationBut 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 modelHowever 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
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 biochemicalphysiological 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 TMAOp-cresyl sulfate PCS phenyl sulfate PS indoxyl sulfate IS and indole-3-acetic acid IAAThe 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 modificationsRecently an animal study suggested that dapagliflozin subtly improve the composition of the gut microbiota in mice with T2D and another preliminary clinical study didnt observe a modification in the fecal microbiome after dapagliflozin initiationBut 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 modelHowever 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
Detailed Description:
None
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
False
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None