Ignite Creation Date:
2024-07-17 @ 11:42 AM
Last Modification Date:
2024-10-26 @ 3:34 PM
Study NCT ID:
NCT06499948
Status:
RECRUITING
Last Update Posted:
2024-07-15
First Post:
2024-07-07
Brief Title:
Albuminuria Lowering Effect of Dapagliflozin Spironolactone and Their Combination in Adult Patients with Alport Syndrome COMBINE-ALPORT
Sponsor:
Stefan Lujinschi
Organization:
Institutul Clinic Fundeni
Study Overview
Official Title:
A Unicentric Randomized Open-label Cross-over Clinical Trial to Assess the Effect of Dapagliflozin Spironolactone and Their Combination When Added to Renin-Angiotensin System Blockade on Lowering Urine Albumin-to-Creatinine Ratio in Adult Patients with Alport Syndrome
Status:
RECRUITING
Status Verified Date:
2024-05
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:
COMBINE-ALPORT
Brief Summary:
Alport syndrome AS is one of the most common monogenic kidney disorders oftentimes leading to end-stage kidney disease ESKD As AS is caused by variants involving type IV collagen genes COL4 there is no specific treatment aimed at stopping the disease progression Large studies have validated the use of renin-angiotensin-system inhibitors RASis in AS as these drugs can slow the progression to chronic kidney disease CKD These studies included mainly pediatric patients with X-linked AS XLAS There is a lack of data regarding the therapeutic approach in patients having autosomal dominant AS ADAS
Recent data from murine studies suggest that the combined therapy using a sodium-glucose-cotransporter 2 inhibitor SGLT2i and a mineralocorticoid receptor blocker MRB can reduce proteinuria in COL4A3 knock-out mice The albuminuria lowering effect of this combination was demonstrated in other non-diabetic nephropathies Used in monotherapy both drugs have showed protective and antifibrotic effects in murine models of AS
The COMBINE-ALPORT trial aims to evaluate the albuminuria lowering effect of Dapagliflozin Spironolactone and their combination in adult patients with genetically proven AS when added to maximum tolerated RASi dose As proteinuria is the primary driver of CKD progression and the change in albuminuria is widely used as a surrogate endpoint for kidney disease progression lowering albuminuria will delay the onset of ESKD in patients with AS
The main hypothesis of COMBINE-ALPORT trial is that the association of Dapagliflozin and Spironolactone will significantly reduce albuminuria in adult patient with AS
The patients will be randomized to receive either Spironolactone or Dapagliflozin on top of standard therapy maximum RASi dose in a cross-over trial design 4 weeks of treatment followed by 4 weeks of wash-out Finally the whole cohort will receive both Spironolactone and Dapagliflozin for another 4 weeks
The patients will visit the clinic every 4 weeks for checkups and tests
The primary outcome is the effect on albuminuria by each treatment regimen Spironolactone Dapagliflozin or their combination
Recent data from murine studies suggest that the combined therapy using a sodium-glucose-cotransporter 2 inhibitor SGLT2i and a mineralocorticoid receptor blocker MRB can reduce proteinuria in COL4A3 knock-out mice The albuminuria lowering effect of this combination was demonstrated in other non-diabetic nephropathies Used in monotherapy both drugs have showed protective and antifibrotic effects in murine models of AS
The COMBINE-ALPORT trial aims to evaluate the albuminuria lowering effect of Dapagliflozin Spironolactone and their combination in adult patients with genetically proven AS when added to maximum tolerated RASi dose As proteinuria is the primary driver of CKD progression and the change in albuminuria is widely used as a surrogate endpoint for kidney disease progression lowering albuminuria will delay the onset of ESKD in patients with AS
The main hypothesis of COMBINE-ALPORT trial is that the association of Dapagliflozin and Spironolactone will significantly reduce albuminuria in adult patient with AS
The patients will be randomized to receive either Spironolactone or Dapagliflozin on top of standard therapy maximum RASi dose in a cross-over trial design 4 weeks of treatment followed by 4 weeks of wash-out Finally the whole cohort will receive both Spironolactone and Dapagliflozin for another 4 weeks
The patients will visit the clinic every 4 weeks for checkups and tests
The primary outcome is the effect on albuminuria by each treatment regimen Spironolactone Dapagliflozin or their combination
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?:
False
Is an FDA AA801 Violation?:
None